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1.
Objective: To determine the effects of hawthorn extract on serum lipid levels, pathological changes in aortic atherosclerosis plaque, inflammatory factors, and apoptosis-related protein and mRNA expression in apolipoprotein E gene knockout(ApoE~(-/-)) mice. Methods: Thirty-six ApoE~(-/-) mice were fed with a high-fat diet starting at the age of 8 weeks. Mice were randomly divided into 3 groups by a random number table including model group, hawthorn extract group, and simvastatin group, 12 mice in each group. Twelve 8-week-old C57BL/6 mice were fed a basic diet and served as control. The mice in the control and model groups were administered 0.2 mL saline daily, the mice in the hawthorn extract and simvastatin groups were administered with 50 mg/kg hawthorn extract or 5 mg/kg simvastatin daily for 16 weeks. After 16 weeks, plasma lipids including total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol(HDL-C) were determined by an enzymatic assay. Aortic atherosclerotic lesions were observed by light microscopy, scanning and transmission electron microscopy, respectively. Plasma levels of monocyte chemoattractant protein-1(MCP-1), interleukin-1β(IL-1β), adiponectin(APN), and hypersensitive C-reactive protein(hs-CRP) were measured by enzyme-linked immunosorbent assay(ELISA). Protein and mRNA expressions of Bax and Bcl-2 in the aorta were assessed by Western blotting and quantitative real-time polymerase chain reaction(qR T-PCR), respectively. Results: Compared to the control group, the plasma levels of TC, TG and LDL-C were significantly increased and HDL-C were significantly decreased in the model group(P0.01). Compared to the model group, treatment with hawthorn extract significantly decreased the plasma levels of TC, TG, and LDL-C and increased the plasma level of HDL-C in ApoE~(-/-)mice(P0.01). The levels of MCP-1, IL-1β, and hs-CRP in the model group were significantly increased and APN was significantly decreased compared with the control group(P0.01). Compared to the model group, treatment with hawthorn extract decreased the levels of MCP-1, IL-1β, and hs-CRP and increased the APN level(P0.01). Compared to the control group, the protein and mR NA expression of Bax in the model group were significantly increased and the expression of Bcl-2 was significantly decreased(P0.01). Hawthorn extract also reduced the protein and mR NA expression of Bax and increased the Bcl-2 expression in the aorta(P0.01). Conclusion: Hawthorn extract has anti-atherosclerosis and stabilizing unstable plaque effects. The mechanism may be related to the inflammation and apoptosis signaling pathways. 相似文献
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Background Chronic intermittent hypoxia (CIH) is the most important pathophysiologic feature of sleep apnea syndrome (SAS). To explore the relationship between SAS and dementia, the effects of CIH on the expression of Nip3, neuron apoptosis and β-amyloid protein deposit in the brain cortex of the frontal lobe of mice were evaluated in this study.
Methods Thirty male ICRmice'were divided into four groups: control group (A, n=-10, sham hypoxia/reoxygenation), 2 weeks CIH group (B, n=5), 4 weeks CIH group (C, n=-5), and 8 weeks CIH group (D, n=10). The ICR mice were placed in a chamber and exposed to intermittent hypoxia (oxygen concentration changed periodically from (21.72±0.55)% to (6.84±0.47)% every two minutes, eight hours per day). Neuron apoptosis of the cortex of the frontal lobe was detected by means of terminal deoxy-nucleotidyl transferase-mediated in situ end labeling (TUNEL). Immunohistochemical staining was performed for measuring expression of Nip3 and β-amyloid protein. The ultrastructure of neurons was observed under a transmission electron microscope.
Results TUNEL positive neurons in each square millimeter in the cortex of the frontal lobe were categorized by median or Riinto group A (1, 5.5), group B (133, 13), group C (252, 21), and group D (318, 24). There were significant differences among the above four groups (P=0.000). The significance test was performed between the control group and each CIH group respectively: group A and B (P 〉0.05); group A and C (P 〈0.01); and group A and D (P 〈0.005). The number of apoptotic neurons kept increasing in the ICR mice under CIH condition, and reached the peak in the group D, but there was no significant difference between groups B and C, between groups B and D, and between groups C and D. Nip3 positive neurons in each square millimeter in the cortex of the frontal lobe in each group were calculated by median or Ri as follows: group A (2, 5.5), group B (117, 13), group C (227, 26.2), and group D(479, 21.4). There were significant differences among the four groups (P=0.000). The statistical test was performed between the control group and each CIH group respectively: groups A and B (P 〉0.05); groups A and C (P〈0.005); and groups A and D (P 〈0.005). There was no significant difference between groups B and C, groups B and D, and groups C and D. The expression of Nip3 was closely correlated with neuron apoptosis in the brain (P 〈0.05). The expression of β-amyloid protein in the brain of mice was negative in all CIH groups and the control group. Ultrastructure observation showed karyopyknosis of nucleus, swelling of chondriosomes, deposit of lipofuscins and degeneration of neural sheath in all CIH groups but not in the control group. Conclusion The results of this study indicate that CIH could up-regulate the expression of Nip3, and result in neuron apoptosis and ultrastructural changes in neurons of the frontal cortex. 相似文献
Methods Thirty male ICRmice'were divided into four groups: control group (A, n=-10, sham hypoxia/reoxygenation), 2 weeks CIH group (B, n=5), 4 weeks CIH group (C, n=-5), and 8 weeks CIH group (D, n=10). The ICR mice were placed in a chamber and exposed to intermittent hypoxia (oxygen concentration changed periodically from (21.72±0.55)% to (6.84±0.47)% every two minutes, eight hours per day). Neuron apoptosis of the cortex of the frontal lobe was detected by means of terminal deoxy-nucleotidyl transferase-mediated in situ end labeling (TUNEL). Immunohistochemical staining was performed for measuring expression of Nip3 and β-amyloid protein. The ultrastructure of neurons was observed under a transmission electron microscope.
Results TUNEL positive neurons in each square millimeter in the cortex of the frontal lobe were categorized by median or Riinto group A (1, 5.5), group B (133, 13), group C (252, 21), and group D (318, 24). There were significant differences among the above four groups (P=0.000). The significance test was performed between the control group and each CIH group respectively: group A and B (P 〉0.05); group A and C (P 〈0.01); and group A and D (P 〈0.005). The number of apoptotic neurons kept increasing in the ICR mice under CIH condition, and reached the peak in the group D, but there was no significant difference between groups B and C, between groups B and D, and between groups C and D. Nip3 positive neurons in each square millimeter in the cortex of the frontal lobe in each group were calculated by median or Ri as follows: group A (2, 5.5), group B (117, 13), group C (227, 26.2), and group D(479, 21.4). There were significant differences among the four groups (P=0.000). The statistical test was performed between the control group and each CIH group respectively: groups A and B (P 〉0.05); groups A and C (P〈0.005); and groups A and D (P 〈0.005). There was no significant difference between groups B and C, groups B and D, and groups C and D. The expression of Nip3 was closely correlated with neuron apoptosis in the brain (P 〈0.05). The expression of β-amyloid protein in the brain of mice was negative in all CIH groups and the control group. Ultrastructure observation showed karyopyknosis of nucleus, swelling of chondriosomes, deposit of lipofuscins and degeneration of neural sheath in all CIH groups but not in the control group. Conclusion The results of this study indicate that CIH could up-regulate the expression of Nip3, and result in neuron apoptosis and ultrastructural changes in neurons of the frontal cortex. 相似文献
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The Effect of Dendrobium Nobile Lindl. Alkaloids on the Protein Expression of Aβ42,APP and BACE1 of Hippocampus in db/db Mice
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HUANG Juan ZHANG Ming-hui XU Yun-yan YANG Xiao-hui LIU Yuan WU Qin SHI Jing-shan 《神经药理学报》2017,7(2):49
Objective:Beta-amyloid (Aβ) deposition is considered as vital factor leading to cognitive impairment in Alzheimer’s disease( AD).In addition,there are pathophysiological connections between Type 2 Diabetes Mellitus (T2DM) and AD. Diabetic patients have higher incidences of cognitive impairment and hence they are more at the risk of developing AD. As one of the active compounds of Dendrobium nobile Lindl. Dendrobium nobile Lindl. Alkaloids (DNLA) has the effect of protecting the nervous system and decreased the level of fasting blood glucose (FBG) in T2DM model mice. In this study,we attempted to investigate effects of DNLA on the proteins expression of APP,BACE1 and Aβ42 of hippocampus in db/db mice. Methods:10 male C57BL/KsJ mice were
control group. And 4-week-old mice male db/db mice were randomly divided into four groups:model,DNLA-L( 20 mg·kg-1),DNLA-M( 40 mg·kg-1),and DNLA-H (80 mg·kg-1),there are 9 mice in each group. After mice were treated with different concentration DNLA by gavaged for 17 weeks. The protein expression of β-amyloid 42 (Aβ42),β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) and amyloid precursor protein (APP) were examined by Western Blotting. Results:Compared with control group,not only the protein expression of Aβ42,but also BACE1 and APP was signifi cantly increased in hippocampus of model group. Moreover,DNLA signifi cantly decreased the protein expressions of Aβ42,BACE1 and APP in hippocampus of db/db mice compared with model group,and decreased in a dosedependent manner. Conclusion:DNLA can decrease the protein expressions of Aβ42 in hippocampus of db/ db mice. And the mechanism may be involved the decrease of BACE1 and APP. 相似文献
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In order to observe the effect of Bushenantai recipe on the expression of endometrial leukemia-inhibitory factor (LIF) in mice with embryonic implantation dysfunction (EID), 120 Kunming mice post coition were randomized into three groups: normal control group, model group and traditional Chinese medicine group (TCM group) (n=40 in each group). Uterus was collected on the pregnancy day (Pd) 4, 5, 6 after an intravenous injection of Evan's blue. The endometrium was dyed by Evan's blue and the mean points of response were observed on Pd 5. The expression of LIF mRNA and protein was detected by RT-PCR and immunohistochemistry respectively and analyzed statistically by image system. The results showed that the number of implantation sites in model group was remarkably less than in normal control group and TCM group. There was no significant difference between normal control group and TCM group. The expression of LIF mRNA and protein in model group was delayed. Bushenantai recipe could increase the expression of LIF mRNA and protein in endometria of mice with EID. It was suggested that Bushenantai recipe could improve embryo implantation of mice with EID by promoting the endometrial LIF expression and endometrial decidualization. 相似文献
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HUANG Jing CHEN Yu-juan BIAN Wei-hong YU Jing ZHAO Yu-wu LIU Xue-yuan 《中华医学杂志(英文版)》2010,123(10):1311-1314
Background Neuropathologically, Alzheimer disease (AD) is characterized by the presence of extracellular plaques enriched in β-amyloid peptides; however, the mechanism by which it results in the neurotoxicity is uncertain. The purpose of this study was to investigate whether it would prompt the progress of Alzheimer disease via enhancement of aberrant phosphorylated tau that results from its increased kinase gene expression. Methods Twenty-four male rats were divided into three groups, and each group had 8 rats: control, sham-operated, and Aβ25-35 injected AD model groups. AD rat models were created by unilateral injections of Aβ25-35 into the amygdala. The hyperphosphorylated tau protein was estimated by immunohistochemistry with paired helical filament-1 (PHF-1) antibody and paired helical filament-tau (AT8) antibody. The expressions of glycogen synthase kinase-3β (GSK-3β) and p38 mitogen-activated protein kinase (P38MAPK) mRNA were observed by in situ hybridization. Results Compared with the control and sham-operated groups, the evaluation of paired AT8 and paired helical filament-1 (PHF-1) in the cortexes and hippocampus of the AD model group showed the numbers of AT8 and PHF-1 positive cells, as well as the optical density (OD) values of the proteins were significantly higher (AT8: in CA2: 0.318±0.037 vs. 0.135±0.028, 0.136±0.031; in frontal cortex: 0.278±0.040 vs. 0.130±0.028, 0.190±0.037. PHF-1 : in CA2: 0.386±0.034 vs. 0.139±0.010, 0.193±0.041; in frontal cortex: 0.395±0.050 vs. 0.159±0.030, 0.190±0.044, respectively, P 〈0.01); the number of GSK-3β mRNA and P38MAPK mRNA positive cells of the AD model group, as well as the OD values, also increased significantly in the cortexes, hippocampus (GSK-3β-mRNA: in CA2:0.384±0.012 vs. 0.190±0.015, 0.258±0.064; in frontal cortex: 0.398±0.018 vs. 0.184±0.031, 0.218±0.049. P38MAPK mRNA: in CA2:0.409±0.038 vs. 0.161±0.041, 0.189±0.035; in frontal cortex: 0.423±0.070 vs. 0.160±0.032, 0.203±0.053, respectively, P 〈0.01). Conclusion Unilateral injection of Aβ25-35 into the rat amygdala increases the generation of aberrant phosphorylated tau by increasing GSK-3β and PasMAPKgene expression, that accelerates the process of Alzhemer's disease. 相似文献
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Summary: Under global cerebral ischemia, the effect of different brain temperature on cerebral ischemic injury was studied. Male Sprague-Dawley rats were divided into normothermic (37-38℃) ischemia, mild hypothermic (31 32℃) ischemia, hyperthermic (41-42℃) ischemia and sham-operated groups. Global cerebral ischemia was established using the Pulsinelli four-vessel occlusion model and brain temperature was maintained at defined level for 60 min after 20omin ischemia. The expression of c-fos protein and the levels of malondialdehyde (MDA) and lactate in brain regions were detected by immunochemistry and spectrophotometrical methods, respectively. C-fos positive neurons were found in the hippocampus and cerebral cortex after cerebral ischemia reperfusion. Mild hypothermia increased the expression of c-fos protein in both areas, whereas hyperthermia decreased the expression of c-los protein in the hippocampus at 24 h reperfusion, and the cerebral cortex at 48 h reperfusion when compared to normothermic conditions. In normothermic, mild hypothermic and hyperthermic ischemia groups, the levels of MDA and lactate in brain tissue were increased at 24, 48 and 72 h reperfusion fol- lowing 20-min ischemia as compared with the sham-operated group (P〈0.01). The levels of MDA and lactate in mild hypothermic group were significantly lower than those in normothermic group (P〈0.01). It is suggested that brain temperature influences the translation of the immunoreactive protein product of c-fos after global cerebral ischemia, and MDA and lactate are also affected by hypothermia and hyperthermia. 相似文献
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The effects of ATP-sensitive mitochondrial K + channel(mitoK ATP) on mitochondrial membrane potential(Δψm),cell proliferation and protein kinase C alpha(PKCα) expression in airway smooth muscle cells(ASMCs) were investigated.Thirty-six Sprague-Dawley(SD) rats were immunized with saline(controls) or ovalbumin(OVA) with alum(asthma models).ASMCs were cultured from the lung of control and asthma rats.ASMCs were treated with diazoxide(the potent activator of mitoK ATP) or 5-hydroxydencanote(5-HD,the inhibitor of mitoK ATP).Rhodamine-123(R-123) was used to detect Δψm.The expression of PKCα protein was examined by using Western blotting,while PKCα mRNA expression was detected by using real-time PCR.The proliferation of ASMCs was measured by MTT assay and cell cycle analysis.In diazoxide-treated normal ASMCs,the R-123 fluorescence intensity,protein and mRNA levels of PKCα,MTT A values and percentage of cells in S phase were markedly increased as compared with untreated controls.The ratio of G 0 /G 1 cells was decreased(P<0.05) in diazoxide-treated ASMCs from normal rats.However,there were no significant differences between the ASMCs from healthy rats treated with 5-HD and the normal control group.In untreated and diazoxide-treated ASMCs of asthmatic rats,the R-123 fluorescence intensity,protein and mRNA levels of PKCα,MTT A values and the percentage of cells in S phase were increased in comparison to the normal control group.Furthermore,in comparison to ASMCs from asthmatic rats,these values were considerably increased in asthmatic group treated with diazoxide(P<0.05).After exposure to 5-HD for 24 h,these values were decreased as compared with asthma control group(P<0.05).In ASMCs of asthma,the signal transduction pathway of PKCα may be involved in cell proliferation,which is induced by the opening of mitoK ATP and the depolarization of Δψm. 相似文献
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The expression profile in the mouse hepatitis B virus X (HBx)-transfected model was investigated in order to lay a foundation for further study on the implication of cytokines expression in hepatitis B virus (HBV) infection.Hydrodynamic injection method via the tail vein was used to establish the animal HBx-transfected model.By using microassay,the differential expression of gene in each group was analyzed,which was further confirmed by using real-time PCR and semi-quantitative PCR.Most of chemokine genes such as Ccl2,Ccl5,Ccl9,MIG and IP-10 were up-regulated in the HBx-transfected mouse model versus the control mice,which was coincided with the microarray results.Western blotting and immunohistochemistry were applied to detect the expression of MIG and IP-10 in the liver tissues.Simultaneously,ELISA was adopted to measure the content of IFN-γ in the liver tissues.DNA microassay revealed that the expression of 611 genes changed in HBx-transfected mice as compared with that in pCMV-tag2B-transfected mice,and most of the screened chemokines were up-regulated (including MIG and IP-10).Additionally,IFN-γ protein levels were increased by 20.7% (P<0.05) in pCMV-tag2B-HBx-transfected mice as compared with the untreated mice.IFN-γ protein levels were reduced by 53.9% (P<0.05) in pCMV-tag2B-transfected mice as compared with the untreated mice,which was consistent with the up-regulation of MIG and IP-10.It was suggested HBx transfection could induce the expression of MIG and IP-10 in the liver tissues,which might play the roles in HBV-related liver immunity and cytokines-mediated antiviral effect. 相似文献
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Objective:To investigate the protective effect of Chinese herbal formula Huangqin Decoction(HQD)on ulcerative colitis mouse model induced by dextran sulphate sodium(DSS)and human intestinal epithelial cell injury induced by tumour necrosis factor-α(TNF-α).Methods:In vivo,30 male C57BL/6 mice were divided into 5 groups using a random number table(n=6 per group),including control,DSS,5-aminosalicylic acid(5-ASA),HQD low-(HQD-L)and high-dose(HQD-H)groups.The colitis mouse model was established by 3%(w/v)DSS water for 5 days.Meanwhile,mice in the HQD-L,HQD-H and 5-ASA groups were administrated with 100,200 mg/kg HQD or 100 mg/kg 5-ASA,respectively,once daily by gavage.After 9 days of administration,the body weight,disease activity index(DAI)score and colon length of mice were measured,the pathological changes of colons were analyzed by hematoxylin-eosin staining(HE)staining,and the levels of serum interleukin(IL)-6,IL-1βand TNF-αwere measured by enzyme linked immunosorbent assay.In vitro,the human colon epithelial normal cells(FHC cells)were exposed to HQD(0.6 mg/mL)for 12 h and then treated with TNF-α(10 ng/mL)for 24 h.The tight junction(TJ)protein expression levels of Claudin-4 and Occludin,and the protein phosphorylation levels of p65 and inhibitor of nuclear factor kappaB(NF-κB)-α(IκBα)were measured by Western blot.Results:In vivo,compared with the DSS group,HQD-H treatment attenuated the weight loss and reduced DAI score of mice on the 8th day(P<0.05).Moreover,HQD-H treatment ameliorated the colon shortening in the DSS-induced colitis mice(P<0.05).HE staining showed HQD attenuated the pathological changes of colitis mice,and the histological scores of HQD-H and 5-ASA groups were significantly decreased compared with the DSS group(P<0.05).Meanwhile,HQD-H and 5-ASA significantly decreased the serum IL-1β,IL-6 and TNF-αlevels of mice(P<0.05).In vitro experiments showed that HQD up-regulated Occludin and Claudin-4 protein expressions and inhibited p-p65 and p-IκBαlevels in FHC cells compared with the TNF-αgroup(P<0.05).Conclusion:HQD significantly relieved the symptoms in DSS-induced colitis mice by inhibiting pro-inflammatory cytokines expression and maintained the homeostasis of TJ protein in FHC cells by suppressing TNF-α-induced NF-κB activation. 相似文献
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Objective:To observe the effect of the total alkaloids of Dendrobium nobile Lindl on the learning and memory impairment of APP/PS1 transgenic mice. Methods:Seven months male APP/PS1 transgenic mice (n=24) were randomly divided into two groups:APP/PS1+vehicle and APP/ PS1+DNLA(the total alkaloids of Dendrobium nobile Lindl) groups. Age-matched male wild-type( WT)littermates (n=24) were randomly divided into two groups:WT+vehicle and WT+DNLA groups. The normal group and APP / PS1 group were garaged with normal volume of saline( NS) for 6 consecutive months. The mice in the normal administration group and APP/PS1-administered group were given the daily total alkaloid of Dendrobiumnobile 40 mg·kg-1. Morris water maze was used to detect learning and memory ability in mice. At the end of the behavioral test,the cortical area of senile plaques were detected in the mice by anesthesia,and the survival of the hippocampal neurons was detected by Nissl’s staining.Transmission electron microscope was performed to observe neuron structure and synaptic structure in hippocampus. The levels of IL-1β were measured by ELISA .The levels of Aβ1-40,Aβ1-42 and the expression of GFAP,IL-6,COX-2,p-NF-ΚB,p-p38,PSD95 and SYP in hippocampus were detected by Western blot. Results:Compared with WT+vehicle group,the mean escape latency was markedly increased and the time percentage in target quadrant showed notable decrease in APP/PS1+vehicle group. The number of neurons were significantly reduced in hippocampal CA1 region. The results of transmission electron microscope showed that the structure of neuron and synaptic structure were damaged and the number of synaptic density was decreased. The amyloid plaques,Aβ1-40,Aβ1-42 contents the protein expression of GFAP,IL-6,COX-2,p-NF-κB and p-p38 were increased,meanwhile,the protein expression of PSD95 and SYP were dramatically decreased in the hippocampus in APP/PS1+vehicle group. These effects in WT+DNLA group showed no notable differences compared to the WT+vehicle group. However,compared with APP/PS1+vehicle group,the mean escape latency was decreased and the time percentage in target quadrant was notably increased in APP/PS1+DNLA. Moreover,the number of neurons were significantly increased in hippocampal CA1 region. The
structure of neuron and synaptic structure was improvement Furthermore,the amyloid plaques,Aβ1-40,Aβ1-42 contents,GFAP,IL-6,COX-2,p- NF-κB and p-p38 expression were decreased in thehippocampus,the protein expression of PSD95 and SYP were significantly increased in APP/PS1+DNLA group. Conclusions:Under the experimental conditions,DNLA attenuates the learning and memory loss of Alzheimer’s disease mice and reduces the number of senile plaques and increases the number of surviving neurons. The mechanism may be related to level of Aβ,activation of astrocytes,activation of astrocytes,inhibition of NF-κB and p38 and improvement of synaptic dysfunction. 相似文献
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The aim of this study was to investigate the possible beneficial effects of Fenofibrate on renal ischemia-reperfusion injury(IRI) in mice and its potential mechanism. IRI was induced by bilateral renal ischemia for 60 min followed by reperfusion for 24 h. Eighteen male C57BL/6 mice were randomly divided into three groups: sham-operated group(sham), IRI+saline group(IRI group), IRI+Fenofibrate(FEN) group. Normal saline or Fenofibrate(3 mg/kg) was intravenously injected 60 min before renal ischemia in IRI group and FEN group, respectively. Blood samples and renal tissues were collected at the end of reperfusion. The renal function, histopathologic changes, and the expression levels of pro-inflammatory cytokines [interleukin-8(IL-8), tumor necrosis factor alpha(TNF-α) and IL-6] in serum and renal tissue homogenate were assessed. Moreover, the effects of Fenofibrate on activating phosphoinositide 3 kinase/protein kinase B(PI3K/Akt) signaling and peroxisome proliferator-activated receptor-α(PPAR-α) were also measured in renal IRI. The results showed that plasma levels of blood urea nitrogen and creatinine, histopathologic scores and the expression levels of TNF-α, IL-8 and IL-6 were significantly lower in FEN group than in IRI group. Moreover, Fenofibrate pretreatment could further induce PI3K/Akt signal pathway and PPAR-α activation following renal IRI. These findings indicated PPAR-α activation by Fenofibrate exerts protective effects on renal IRI in mice by suppressing inflammation via PI3K/Akt activation. Thus, Fenofibrate could be a novel therapeutic alternative in renal IRI. 相似文献
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Objective:To study the effects of Zuogui Pill(左归丸,ZGP)and Yougui Pill(右归丸,YGP)on the expressions of brain-derived neurotrophic factor(BDNF)and cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)signaling of axonal regeneration in the Lewis rats with experimental autoimmune encephalomyelitis(EAE),in order to explore the possible mechanism of ZGP and YGP on promoting axonal regeneration.Methods:The rats were randomly divided into normal control(NC),model(MO),prednisone acetate(PA),ZGP and YGP groups.The EAE model of rat was established by injecting antigen containing myelin basic protein(MBP)68-86.The brain and spinal cord were harvested on the 14th and 28th day postimmunization(PI),the protein and mRNA expression of BDNF and PKA in the brain and spinal cord of rats were detected by Western blot analysis and real-time quantitative polymerase chain reaction(PCR),and the cAMP levels were detected by using enzyme-immunoassay method.Results:(1)On the 28th day PI,the mRNA expression of BDNF in brain white matter and spinal cord of rats in ZGP and YGP groups were up-regulated,especially in YGP group(P〈0.05 or P〈0.01).(2)On the 14th day PI,the cAMP levels in brain white matters significantly increased in PA and YGP groups compared with MO group(P〈0.05 or P〈0.01),and the cAMP level in YGP group was higher than that in ZGP group(P〈0.05).The cAMP level in spinal cord also significantly increased in YGP group compared with MO,PA and ZGP groups,respectively(P〈0.01).(3)On the 14th day PI,the PKA expression in spinal cord of rats in ZGP group was significantly decreased compared with MO and YGP groups,respectively(P〈0.05).(4)On the 28th day PI,there was a positive correlation between cAMP and PKA expression in the brain white matter of YGP rats.Conclusions:The results suggest that ZGP and YGP may promote axonal regeneration by modulating cAMP/PKA signal transduction pathway,but the targets of molecular mec 相似文献
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Nuclear factor- κB in signal conduction of protein kinase C in T lymphocytes from an asthmatic guinea pig model 总被引:9,自引:0,他引:9
Objective To explore the role of nuclear factor- κB (NF- κB) in the signal conduction of protein kinase C (PKC) regulated proliferation, apoptosis and expression of Th2 cytokines - interleukin- 4 (IL- 4) and interleukin- 5 (IL- 5) of T lymphocytes in the bronchial alveolus lavage fluid (BALF).Methods T lymphocytes were isolated and purified from BALF of asthmatic guinea pigs in normal and asthmatic groups, and were stimulated with PKC agitator phorbol 12- myristate 13- acetate (PMA) and NF- κB inhibitor pyrrolidine dithiocarbamate (PDTC), respectively.The expressions of NF- κB, IL- 4 and IL- 5 mRNA and protein, the proliferation and apoptosis of T lymphocytes were observed by immunohistochemistry, in situ hybridization, ELISA, MTT and TUNEL, respectively. Results The activation of NF- κB, proliferation response, and expression of IL- 4 and IL- 5 mRNA and protein in T lymphocytes stimulated by PMA were significantly higher than those of their blank control (P<0.01), while those indexes of T lymphocytes stimulated by PMA and PDTC simultaneously were significantly lower than those stimulated by PMA alone (P<0.01).The apoptotic index of T lymphocytes stimulated with PMA were significantly lower than that of their blank control (P<0.01), and the apoptotic index of asthmatic guinea pig T lymphocytes stimulated with PMA and PDTC simultaneously were significantly higher than that stimulated by PMA alone (P<0.01).The significant positive correlations were found between the activation of NF- κB and the proliferation (r=0.64, P<0.001), and the expression of IL- 4 and IL- 5 mRNA and protein of T lymphocytes, respectively (r=0.55-0.68, P<0.001).There was also significant negative correlation between the activation of NF- κB and apoptosis of T lymphocytes (r=0.62, P<0.001). Conclusions NF- κB may participate in the signal conduction of PKC regulated proliferation, apoptosis and expression of IL- 4 and IL- 5 of T lymphocytes in asthma.The activation of NF- κB in PKC signal conduction pathway of T lymphocytes may play an important role in the pathogenesis of asthma. 相似文献
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Effect of pre-electroacupuncture on p38 and c-Fos expression in the spinal dorsal horn of rats suffering from visceral pain 总被引:1,自引:0,他引:1
Background Acupuncture is an effective way to relieve pain, but the mechanism by which electroacupuncture (EA) decreases the visceral pain state still remains unclear. This study aimed to evaluate the effects of pre-electroacupuncture on pain behaviors, p38 phosphorylation, and c-Fos protein and mRNA expression in both the colonic wall and spinal dorsal horn of rats suffering from visceral pain. This study also investigated the probable signaling regulatory mechanism of the analgesic effect induced by electroacupuncture. Methods All rats were randomized into the control (Con) group, the Con+EA group, the visceral pain (VP) group, and VP+EA group (n=8 for all groups). The visceral pain model was established using 40 ul of 5% formalin solution injected into the colon of rats. EA was applied to the bilateral Jiaji acupoints for 20 minutes before application of visceral pain. Parameters for EA were set at a continuous wave (20 Hz) and intensity where the rats shook their whiskers but did not scrabble (≤1 mA). The visceral pain score was recorded and the expressions of p38 and c-Fos protein were detected using Western blotting. Real-time quantitative PCR was also used to determine the expression of c-Fos mRNA. Results Rats in the VP group immediately presented with obvious visceral pain behaviors after being injected with formalin. p38 activity and c-Fos protein and mRNA expression in both the colonic wall and spinal dorsal horn were higher in the VP group than in the Con group (P 〈0.05). By contrast, visceral pain behaviors were delayed in rats from the VP+EA group. p38 activity and c-Fos protein and mRNA expression were lower in the VP+EA group than that in the VP group (P〈0.01). Conclusions Pre-electroacupuncture of the Jiaji acupoint has prophylactic analgesic effects on rats suffering from visceral pain. The p38 signal transduction pathway may be partly involved in the regulatory mechanism of this analgesic effect. 相似文献
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Objective:To investigate the effect of GAPT,an extract mixture from Radix Ginseng,Rhizoma Acor tatarinowii,Radix Polygalae and Radix Curcuma(containing ingredient of turmeric),etc.on expression of tau protein and its phosphorylation related enzyme in hippocampal neurons of APPV717I transgenic mice.Methods:Sixty three-month-old APPV717I transgenic mice were randomly divided into model group,donepezil group[0.92 mg/(kg·d)],the low,medium and high dosage of GAPT groups[0.075,0.15,0.30 g/(kg·d),12 in each group],and 12 three-month-old C57BL/6J mice were set as a normal control group,treatments were administered orally once a day respectively,and both the normal group and model group were given 0.5%sodium carboxymethyl cellulose solution.Immunohistochemistry(IHC)and Western blot analysis were used to detect the expression of total tau protein(Tau-5),cyclin-dependent kinase 5(CDK5)and protein phosphatase 2A(PP2A)in hippocampal neurons of experimental mice after 8-month drug administration(11 months old).Results:In the model group,the expression of Tau-5 and CDK5 were increased,whereas the expression of PP2A was decreased in hippocampal neurons,which were significantly different compared with that in the normal group(all P0.01).IHC test indicated the number and area of either Tau-5 or CDK5 positive cells were decreased with a dose-depended way in GAPT groups,and an increase of PP2A.Compared with the model group,the changes were significant in GAPT groups(P0.05 or P0.01).Similar results were shown by Western blot.Conclusion:GAPT could attenuate abnormal hyperphosphorylation of tau protein in hippocampal neurons of APPV717I transgenic mice via inhibiting the expression of CDK5 and activating the expression of PP2A. 相似文献
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Objective: To observe the effects of Huannao Yicong Formula (还脑益聪方, HYF) on learning and memory and it's regulating effect on γ-secretase related anterior pharynx defective 1 (APH-1), presenilin enhancer-2 (PEN-2) signaling pathway, so as to discuss and further clarify the mechanism of HYF on Alzheimer's disease. Methods: Sixty APP/PS1 transgenic mice, randomly allocated into 4 groups, the model group, the donepezil group (0.65 mg/kg), HYF low-dose group (HYF-L, 5.46 g/kg) and HYF high-dose group (HYF-H, 10.92 g/kg), 15 for each group. Another 15 C57BL/6J mice with the same age and same genetic background were allocated into the control group, proper dosage of drugs or distilled water were given by intragastric administration once daily for 12 weeks. After 12 weeks of administration, the learning and memory abilities of mice in each group was evaluated by the morris water maze test, amyloid precursor protein (APP), Aβ1-40 and Aβ1-42 levels in hippocampus were detected by enzyme-linked immunosorbent assay, γ-secretase was detected by dual luciferase assaying, the levels of APH-1a, hypoxia-inducible factor 1α (HIF-1α), cAMP response element-binding protein (CREB) and PEN-2 and their mRNA expression was measured by Western blot and real-time polymerase chain reaction. Results: HYF can ameliorate learning and memory deficits in APP/PS1 transgenic mice by decreasing the escape latency, improving the number of platform crossing and swimming speed (P<0.01, P<0.05). HYF can decrease the levels of APP, Aβ1-40 , Aβ1-42 and the activity of γ-secretase in hippocampus of Alzheimer's disease model mice. HYF can down-regulate the levels of CREB and PEN-2 and the expression of their mRNA. Conclusion: HYF can improve the learning and memory ability by inhibiting the activity of γ-secretase through the CREB/PEN-2 signaling pathway, and this may be one of the therapeutic mechanisms of HYF in Alzheimer's disease. 相似文献