Effect of Wumeiwan on Cytokines TNF-α, IL-6, IL-8, IL-10 and Expression of NF-κBp65 in Rats with Ulcerative Colitis

The effects of Wumeiwan （WMW） on TNF-α, IL-6, IL-8, IL-10 and NF-κBp65 in rats with ulcerative colitis （UC） were investigated, the curative effectiveness of WMW vs salicylazosulfapyridine （SASP） was compared, and the action mechanism was analyzed. Fifty-Six Sprague-Dawley （SD） rats were randomly divided into four groups （n=14 in each group, with equal ratio of male and female）： normal control group, model group, SASP group, and WMW group. Except normal control group, the rat UC models in the remaining three groups were established using the method of 2.4-dinitrochlorobenzene （DNCB） immunization and acetic acid local enema. The rats in model group, SASP group, and WMW group were treated with distilled water, SASP, and WMW respectively. The changes in the symptoms and signs were observed, and levels of IL-6, IL-8, TNF-α, IL-10 and the expression of NF-κBp65 in the colonic tissues were statistically analyzed. The results showed that the levels of IL-6, IL-8, and TNF-α were significantly increased （P〈0.01）, while those of IL-10 significantly reduced （P〈0.01） after establishment of rat UC models as compared with normal control group. The levels of IL-6, IL-8, and TNF-α were obviously lower, but the level of IL-10 was obviously higher in WMW and SASP groups than those in model group （P〈0.05）. The levels of IL-6, IL-8, and TNF-α were lower, while the level oflL-10 was higher in WMW group than in SASP group. NF-κBp65 was expressed negatively or weakly in normal colonic tissues. The positive expression rate of NF-κBp65 in WMW group and SASP group was obviously lower than in model group （P〈0.01）, and there was significant difference between WMW group and SASP group （P〈0.05）. It was concluded that rat UC model was established successfully. WMW could up-regulate the expression of IL-10, down-regulate the expression of TNF-α, IL-6, IL-8, and inhibit the NF-κBp65 activity to adjust immune function, indicating WMW had better curative effects on UC in rats.     

Effect of Dachengqi Decoction on NF-κB p65 Expression in Lung of Rats with Partial Intestinal Obstruction and the Underlying Mechanism

To investigate the effect of Dachengqi decoction on NF-κB p65 expression in lung of rats with partial intestinal obstruction and the underlying mechanism, 30 SD rats were randomly divided into three groups： sham-operation group, model group and Dachengqi decoction treatment group （Dachengqi group）, with 10 animals in each group. The models were made by partially ligating their large intestines outside the body. The pathological changes were analyzed by HE staining. The expression of NF-κB p65 in rats lung were measured by using real-time polymerase chain reaction and immunohistochemistry respectively. Moreover, the expression of caveolin-1 in rats lung was also measured to. Increased edema, interstitial thickening, hemorrhage, and infiltration of inflammatory cells were found in the model group. In contrast, this change was significantly reduced in Dachengqi group as compared with model group. In addition, the up-regulated caveolin-1 and NF-κB p65 were also suppressed by Dachengqi decoction in lung of rats with partial intestinal obstruction. We are led to concluded that the caveolin-l-NF-κB pathway plays an important role in the development of lung injury of rats with partial intestinal obstruction and Dachengqi decoction could down-regulate the expression of caveolin-1 and NF-κB p65 in lung of rats with partial intestinal obstruction.     

Expression of NF-κB in hRPE Cells Stimulated by PDTC and IL-1β

The constitutive expression of nuclear-factor-κB (NF-κB) in human pigment epithelial (hRPE) cells cultivated in vitro and the possible changes when incubated with PDTC and IL-I were investigated. The synchronized hRPE cells in vitro were divided into two groups. In nonPDTC group, hRPE cells were exposed respectively to IL-1β and NS (for detecting the constitutive expressions of NF-κB in hRPE cells) ; In PDTC group, PDTC-pretreated hRPE cells were exposed respectively to IL-1β?Aand NS. (for detecting the constitutive expression of NF-κB in PDTC-pretreated hRPE cells). The expression of NF-κB in hRPE cells in two groups was detected by immunofluorescence stain and flow cytometry. The results showed that the constitutive expression of NF-κB in hRPE cells in vitro was 8.05 %, and increased to 30.26 % by IL-1β. After PDTC pretreatment, the constitutive expression of NF-κB in hRPE cells was decreased to 3.74%, and 3.66 % by IL-l,respectively. It was concluded that the expressions of NF-κB in hRPE cells could be increased significantly by IL-1βand depressed effectively by PDTC. Also, PDTC could significantly inhibit the activation of NF-κB induced by IL-1β.     

Expression and Significance of NF-κB, IL-1β and COX-2 in the Murine Model of Estrogen-dependent Experimental Vulvovaginal Candidiasis

Objective To investigate the possible role of estrogen in the pathogenesis of vulvovaginal candidiasis(VVC). Methods Estrogen-dependent experimental murine model of C. albicans vaginal infection was established by injecting subcutaneously with estradiol benzoate and then 5×106 stationary-phase C. albicans blastoconidia was inoculated intravaginally to mice (group EI), and other 3 groups were set up: estrogen-treated but not infected (group E); estrogen-untreated but infected (group I); normal control (group C). The dynamic change of colony-forming unit (CFU) of cervivovaginal lavage fluid was observed. Vaginal tissues at different time points (d 2, d 4, d 7 and d 14) after inoculation of C. albicans were obtained. In situ hybridization staining was used to detect expression of cyclooxygenase-2 (COX-2) mRNA and expression of nuclear factor-κB (NF-κB) was examined by immuohistochemistry. ELISA was applied to determine the interlenkin-1β (IL-1β) level. Results The constitutional high level expression of COX-2 mRNA in the vaginal tissue of group E was significantly higher than that in group C on d 4 and d 7 (P<0.01), and the optical density (OD) in group EI was higher than that in the other 3 groups (P<0.05). There were higher IL-1a levels in vaginal tissues from d 4 to d 7 postin- oculation in group EI and group I than group C (P<0.01). Furthermore, IL-1β in group EI was markedly elevated on d 4 and d 7 compared with group I (P<0.01). Compared with group C, the expression of NF-κB in group E was increased obviously on d 4 (P<0.01), and there was significant difference between group EI and group Ion d 4 and d 7 (P<0.01). Conclusions In the murine model of estrogen-dependent experimental VVC, estrogen promotes the infection establishment by up-regulating expression of COX-2 via activating NF-κB signal pathway, and the high expression of COX-2 promoted by the interaction of IL-1β and NF-êB after infection formation was involved in persistence of infection.     

Expression of IL-βα and TNF-α in MCMV Myocarditis and Its Role

In order to study the expression of IL-β and TNF-α in the myocardium of MCMV myocarditis and their role in the myocardial damages, 60 BALB/C mice of 4 weeks were randomly divided into two groups: 36 were injected intraperitoneally with MCMV and 24 served as control group. Immunohistochemistry was used to detect IL-β and TNF-α expression in the myocardium, and myocardial lesions were observed histopathologically. Histopathological study on the myocardium from infected mice revealed focal or diffuse lesions characterized by inflammatory cells and degeneration or necrosis of myocytes. The myocardial lesion score showed the degree of inflammatory cell infiltration was slight in MCMV myocarditis. The positive staining signals for IL-β and TNF-α proteins which mainly located in the infiltrating inflammatory cells and degenerative or necrotic myocytes were markedly detectable whereas there were no positive findings in the myocardium of control mice. IL-β and TNF-α was expressed in the myocardium of viral myocarditis murine model induced by MCMV. IL-β and TNF-α may play an important role in the pathogenesis of viral myocarditis.     

加味竹叶石膏汤及其成分可预防大鼠放射性食管炎的发生

Objective:To investigate the effect of Modified Zhuye Shigao Decoction(加味竹叶石膏汤,MZSD)and its components on preventing radiation esophagitis of rats.Methods:One hundred Wistar rats were randomly divided into 5 groups,including the control group,radiation model group,MZSD group,Zhuye Shigeo Decoction(竹叶石膏汤,ZSD)group,and added Ingredients group,20 rats in each group.The model of radiation esophagitis of rat was established by once local radiation of 40 Gy(330 Mulmin)with a high energy linear accelerator.The administration of Chinese medicine was continued for 14 days from 7 days before radiation application in the three treatment groups.On the 7th and 14th day,the serum was isolated and the levels of inflammatory cytoldnes tumor necrosis factor(TNF-α),interleukin 1 13(IL-1β)and IL-8 were tested.The pathological slices of esophagus were obtained,and the pathological changes were observed.During the whole process,weight and food intake were recorded each day.Results:On the 7th day after radiation,the esophagus of rats in the MZSD group was almost intact,and the pathological injury score was significantly lower than that of the radiation model group,ZSD group and added ingredients group(P0.01).Compared with the control group,the body weight and food intake of rats in the radiation model group were significantly decreased,and the levels of TNF-α,IL-1β and IL-8 were significantly increased(P0.05 or P0.01),while the MZSD group showed a significant increase in body weight and food intake,and a significant decrease in the levels of TNF-α,IL-1β and IL-8 compared with the radiation model group,ZSD group and added ingredients group(P0.05 or P0.01).Conclusion:MZSD prevents the development of radiation esophagitis probably by inhibiting the generation and release of the inflammatory cytoldnes TNF-α,IL-1β and IL-8.     

Effects of Propofol on The mRNA Expression of Toll-like Receptor 4 in BV-2 Cells During Mimic Ischemia-Reperfusion Injury In Vitro

This study investigated the effects of propofol on the mRNA expression of Toll-like receptor-4 (TLR4) in BV-2 cells during mimic ischemia-reperfusion (I/R) injury in vitro. BV-2 cells, a mouse microglia line, were cultured and divided into 4 groups at random: control group (group C), ischemia/reperfusion group (group I/R), low-dose propofol (25 μmol/L) intervention group (group PF25) and high-dose propofol (100 μmol/L) intervention group (group PF100). The mRNA expression of TLR4 and NF-κB was measured by means of RT-PCR. TNF-α levels in the supernatants of BV-2 cells were detected by ELISA. The results showed that the mRNA expression of TLR4 and NF-κB was significantly higher in groups I/R, PF25 and PF100 than in group C (P<0.01). And the TNF-α level in the supernatants was elevated in groups I/R, PF25 and PF100 as compared with that in group C (P<0.01). After pre-treatment with propofol, the mRNA expressions of TLR4 and NF-κB and the TNF-α level were significantly decreased in groups PF25 and PF100 in comparison to those in group I/R (P<0.01). And the decrease in those indicators was more significant in group PF100 than in group PF25 (P<0.01). It was concluded that propofol exerted brain-protecting effects during I/R injury by suppressing the mRNA expressions of TLR4 and NF-κB and deceasing the TNF-α level.     

Relationship between the expression of Toll-like receptor 2 and 4 in mononuclear cells and postoperative acute lung injury in orthotopic liver transplantation

Background The aim of this study was to investigate the potential relationship between the dynamic expression of Toll-like receptor 2 and 4 （TLR2/4） in peripheral blood mononuclear cells as well as changes in serum concentration of inflammatory factors and acute lung injury （ALl） in patients after orthotopic liver transplantation （OLT）. Methods The peripheral blood samples of 27 patients （23 men and 4 women with ASA Ⅲ to Ⅳ） who received OLT were collected for measurement of TLR2/4 at T1 （after induction of anesthesia）, T2 （25 minutes after anhepatic phase）, T3 （3 hours after graft reperfusion） and T4 （24 hours after graft reperfusion）. The expression of TLR2/4 in mononuclear cells was measured by flow cytometry. The serum concentrations of tumor necrosis factor （TNF）-α, interleukin （IL）-1β and IL-8 were measured by enzyme-linked immunosorbent assay （ELISA）. Twenty-seven patients were assigned to ALl group （n=-9） and non-ALl group （n=-18） according to the diagnostic criteria of ALl. The expression of TLR2/4 in the ALl group or non-ALl group was analyzed. Results Compared to the non-ALl group, the volumes of blood loss, ascites, total output and transfused red blood cells were higher in the ALl group, and the anhepatic phase lasted longer （P 〈0.05, P 〈0.01）. The expression of TLR2/4 in mononuclear cells increased significantly at T3 and T4, and serum concentrations of TNF-α, IL-1β and IL-8 increased significantly too. There was no significant difference in Child-Turcotte-Pugh （CTP） scores between the ALl group and non-ALl group （P 〉0.05）. The expression of TLR2/4 in mononuclear cells increased significantly at T3 and T4 in the ALl group （P 〈0.05, P〈0.01）. A positive correlation was noted between the expression of TLR4 in mononuclear cells and the serum concentrations of TNF-α, IL-1β （P=0.041, P=0.046） in the ALl group. In the non-ALl group, statistical results showed that the expression level of TLR2/4 in mononuclear cells was not significantly different during the peri-operative period of OLT （besides TLR4 expression at T4）. Compared to expression in mononuclear cells was more significant in the mononuclear cells exceeded that at T1 by one time were more 16. the non-ALl group, the increasing amplitude of TLR2/4 ALl group. The patients whose TLR2/4 expression in likely to suffer from ALl （P=0.013）, with a relative risk of Conclusion The expression level of TLR2/4 in mononuclear cells increases significantly in the peri-operative period of OLT, and it may be a high risk factor for occurrence of postoperative ALl.     

Electroacupuncture Delays Cartilage Degeneration by Modulating Nuclear Factor-κB Signaling Pathway

Objective: To illustrate the molecular mechanisms underlying the therapeutic effects of electroacupuncture(EA) on knee osteoarthritis(OA). Methods: Twenty-seven six-month-old New Zealand white rabbits were allocated into three groups in accordance with a random number table: normal group(no surgery-induced OA; without treatment), model group(surgery-induced OA; without treatment) and EA group [surgery-induced OA; received treatment with EA at acupoints Dubi(ST 35) and Neixiyan(EX-LE 5), 30 min twice a day]. After eight consecutive weeks of treatment, the histopathological alterations in cartilage were observed using optical microscopy and transmission electron microscopy, cartilage degeneration was evaluated by modified Mankin's score principles, the synovial fluid concentration of interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α) and matrix metalloproteinase-3(MMP-3) were evaluated by enzyme-linked immunosorbent assay, and the protein expression levels of IL-1β, IL-6, TNF-α, MMP-3, IκB kinase-β(IKK-β), nuclear factor of α light polypeptide gene enhancer in B-cells inhibitor α(IκB-α) and nuclear factor-κB(NF-κB) p65 were quantified by Western blot analysis. Results: EA treatment significantly improved cartilage structure arrangement and reduced cellular degeneration. The IL-1β, IL-6, TNF-α and MMP-3 of synovial fluid in the EA-treated group were significantly decreased compared with the model group(all P0.01). Compared with the model group, the IL-1β, IL-6, TNF-α, MMP-3, IKK-β and NF-κB p65 protein expressions in cartilage of EA-treated group were significantly decreased(all P0.01), whereas IκB-α expression was significantly up-regulated(P0.01). Conclusion: EA treatment may delay cartilage degeneration by down-regulating inflammatory factors through NF-κB signaling pathway, which may, in part, explain its clinical efficacy in the treatment of knee OA.     

Protective Effect of Norcantharidin on Collagen-Induced Arthritis Rats

Objective: To observe the effect of norcantharidin(NCTD) on collagen-induced arthritis(CIA) rats. Methods: Sixty Sprague-Dawley(SD) rats were randomly divided into 6 groups(n=10): normal group, CIA model group(model group), NCTD low-dose group [1.35 mg/(kg·d)], NCTD middle-dose group [2.7 mg/(kg·d)], NCTD high-dose group [5.4 mg/(kg·d)] and methotrexate(MTX) group [1.8 mg/(kg/w)]. Anesthetized rats were sacrificed by luxation of cervical vertebra after 4 weeks of administration. The arthritis scores were evaluated twice a week. The pathological changes in the ankle joints of rats were observed by hematoxylin-eosin(HE) staining. The serum levels of interleukin(IL) 1β, IL-6, tumor necrosis factor(TNF)-α, vascular endothelial growth factor(VEGF), IL-17 and transform growth factor(TGF) β were detected by enzyme linked immunosorbent assay(ELISA). The mRNA expression of retinoid-related orphan nuclear receptor γ t(ROR γ t) and forkhead box P3(Foxp3) in peripheral blood lymphocytes were confirmed by real-time polymerase chain reaction. Results: MTX and high-dose NCTD not only decreased the arthritis scores but also alleviated the pathological changes in CIA rats' ankle joints compared with the model group(P0.05 or P0.01). All doses of NCTD significantly inhibited the serum levels of IL-6, IL-17 and TNF-α in CIA rats(P0.05). Only middle-and high-dose of NCTD prominently decreased serum IL-1β and TGF-β levels of CIA rats(P0.05). However, NCTD has no effect on vascular endothelial growth factor(VEGF) level in CIA rats. The Foxp3 mRNA expression in all NCTD groups were increased significantly than in the model group(P0.05). The mRNA expression of RORγt in NCTD high-dose group was decreased apparently in comparison with the model group(P0.05). Conclusion: NCTD showed therapeutic effect on CIA rats by inhibition of cytokines and regulation of Th17/Treg cells.     

Effects of Osthole on the Right Ventricle Remodeling in Monocrotaline-Treated Rats

Objective:To investigate the effects of Osthole(Ost) on the right ventricle remodeling in monocrotaline-treated rats,and to explore the mechanisms. Methods:200~220 g male Sprague-Dawley rats were randomly divided into normal control group(Control,n=8),model group(Model,n=8),low dose of Ost treatment group(Ost-L,10 mg·kg~(-1),n=8),high dose of Ost treatment group(Ost-H,20 mg·kg~(-1),n=8) and sildenafil treatment group(Sildenafil,25 mg·kg~(-1),n=8).All rats were given a single dose of MCT 50 mg·kg~(-1) subcutaneously to establish the right ventricle remodeling except normal control group. Then the rats in the Ost and sildenafil treatment group were gavaged once daily from 1 day to 28 days. The other rats in the model group and normal control group were given the same amount of dd H_2O with 0.5% be tween 80. After 28 days of administration,the right ventricular pressure were measured by right heart catheterization. Right ventricle(RV) and left ventricle plus septum(LV+SEP) were weighed separately. RV hypertrophy index(RVHI) were measured by the relative weight ratio of RV to LV+SEP. The morphological change of the RV were executed by light microscope and transmission electron microscope.The cardiomyocytes apoptosis were detected by Td T mediated nick d UTP end-labeling(TUNEL) method using the paraffin-embedded right ventricular tissues. The m RNA expression of Bcl-2,Bok and p53 were examined by real time RT-PCR. The protein expression of Bcl-2,Bax,Bok,IκB,IL-6,TNF-α and the levels of Cleaved caspase 3,p-NF-κB(p65) were detected by western blotting. Results:Compared with the control group,the right ventricular pressure and RVHI were increased obviously(P<0.05),myocardial hypertrophy,structure disorders,mitochondrial swelling and cardiomyocytes apoptosis(P<0.05) were observed in model group. The m RNA expression of Bok and p53 in right ventricular tissues were up-regulated(P<0.05),and the m RNA expression of Bcl-2 was down-regulated in model group(P<0.05).The protein expression of Bax,Bok,IL-6,TNF-α and the levels of Cleaved caspase 3,p-NF-κB(p65) were up-regulated(P<0.05),and the protein expression of Bcl-2 and IκB were down-regulated significantly in model group(P<0.05). Compared with the model group,the right ventricular pressure and RVHI were decreased(P<0.05),myocardial hypertrophy,structure disorders,mitochondrial swelling and cardiomyocytes apoptosis(P<0.05) were improved significantly in Ost and sildenafil treatment group. The m RNA expression of Bok and p53 were downregulated(P<0.05),while the m RNA expression of Bcl-2 was up-regulated(P<0.05) in Ost and sildenafil treatment group. The protein expression of Bax,Bok,IL-6,TNF-α,and the levels of Cleaved caspase 3,p-NF-κB(p65) were down-regulated(P<0.05),and the protein expression of Bcl-2 and IκB were upregulated significantly in Ost and sildenafil treatment group(P<0.05). Conclusions:Ost can resist the RV remodeling induced by MCT in rats,which may be related to these possible mechanisms:(1) Ost inhibits cardiomyocytes apoptosis by regulating Bax/Bcl-2 pathways;(2) Ost attenuates inflammation by inhibiting NF-κB pathway.     

Effect of expression of TGF-beta and TNF-alpha with Qidan granule treatment in rats by bleomycin-induced pulmonary fibrosis

Objective: To evaluate the therapeutic effects and mechanisms of Qidan granule in blemycinA5-induced pulmonary interstitial fibrosis (PIF)in rats. Methods: PIF models were established by blemycinA5-induced in rats. They were treated by Qidan granule and Hydrocortisone respectively. The pathological changes and collagen protein disposition were observed, and the expression of TGF-β, TNF-α proteins were measured by immunohistochemical technique . Results: The pulmonary alveolitis and fibrosis were alleviated remarkably in Qidan granule group compared with those in the model control group and hydrocortisone group (P <0. 01). The expression of TGF-β and TNF-α protein were higher in Qidan granule group than those in normal group , and were significantly less than those in the model control group and in hydrocortisone group (P < 0. 01). Conclusion: Qidan granule would ameliorate the pulmonary alveolitis and fibrosis. TGF-β and TNF-α might play an important role in the development of alveolitis and fibro     

The Therapeutic Effects of Rehmannia Oral Liquid for the Syndrome of Heat Accumulation with Yin Consumption in Esophagus Cancer Patients Undergoing Radiotherapy——A Report of 60 Cases

Objective: To observe the clinical therapeutic effects of Rehmannia Oral Liquid on the syndrome of heat accumulation with Yin consumption in intermediate or late esophagus cancer patients undergoing radiotherapy. Methods: The IFN-α, TNF-α, IL-1β and TGF-β1 levels in sera were determined by the method of ABC-WLISA before and after the treatment with Rehmannia Oral Liquid. At the same time, the observation was carried out on the patient's general condition, symptoms and signs, barium meal or CT examinations, and biopsy. Another 30 cases of esophagus cancer were treated singly with radiotherapy as the control group. Results: Rehmannia Oral Liquid could obviously improve the patient's general condition, and the symptoms and signs after radiotherapy. Based on the X-ray examination and biopsy, the short-term local control rate of the treatment group and the control group was 70.0% and 40.0% respectively, showing a significant difference (P<0.05). Before the treatment, the level of serum IFN-α of both cancer groups was lower and the levels of TNF-α, IL-1β and TGF-β1 were higher than that of normal group. After treatment, the level of IFN-α in both treatment group and control group increased significantly (P<0.01), and the treatment group improved more obviously than the control group (P<0.05). The level of TNF-α of both groups decreased significantly (P<0.01) after treatment, and the level of IL-1β decreased in treatment group and increased in control group without the significant difference as compared with that before treatment. The level of TGF-β1 was significantly increased in control group (P<0.05) and decreased in treatment group (P>0.05) after treatment. The difference between groups was significant (P<0.05). Conclusion: Rehmannia Oral Liquid can obviously reduce the radiotherapy reaction, improve the quality of life, and raise the therapeutic effects. The action mechanism of the Liquid may lie in balancing the cytokine network and regulating the disordered signal transmission.     

Significance of Rosiglitazone Inhibiting TLR4 Expression in Partial Hepatic Ischemia/Reperfusion of Mice

The effect of rosiglitazone as the ligand of peroxisome proliferator-activated receptor γ (PPARγ) inhibiting the TLR4 expression in ischemic lobes in partial hepatic ischemia/reperfusion injury (IRI) in BABL/C mice and the action of rosiglitazone inhibiting the TLR4 receptor-mediated inherent immune response were investigated. The model of the mouse partial hepatic ische- mia/reperfusion injury was established. All the animals were randomly divided into 3 groups: rosiglitazone group, vehicle (dimethylsulphoxide, DMSO) group and sham operation group. The hepatic samples were collected when mice were sacrificed 0, 2, 4 and 6 h after reperfusion following 1 h ischemia to analyze the acute phase of hepatic IRI. The dynamic expression of TlR4 mRNA was de- tected quantitatively by real-time-PCR, and the levels of TNF-α, IL-10 and ALT in portal vein were determined in all groups. After restoration of blood supply, the expression of TLR4 mRNA in ischemic lobes was detected in 0, 2, 4 and 6 h after reperfusion following 1 h ischemia in rosiglitazone group and vehicle group. The most intensive expression of TLR4 mRNA was present at 4 h after reperfusion in ischemic lobes in vehicle group. As compared with vehicle group, the expression of TLR4 mRNA in ischemic lobes in rosiglitazone group was significantly decreased at 4 h after reper- fusion. The level of IL-10 in portal vein was markedly up-regulated in rosiglitazone group as compared with vehicle group. Contrarily, the levels of TNF-α and ALT in portal vein were markedly down-regulated in rosiglitazone group as compared with vehicle group at every time point in mouse partial hepatic IRI model. Rosiglitazone could alleviate the hepatic IRI by inhibiting TLR4 receptor-mediated inherent immune response.     

Effects of simvastatin on the function of dendritic cells in patients with rheumatic arthritis

The present study examined the functional profile of dendritic cells (DCs) in patients with rheumatoid arthritis (RA) and the effects of simvastatin on the function of DCs.A total of 40 patients who was recently diagnosed as having RA were equally assigned to two groups:the routine treatment group (group R) and the routine treatment plus simvastatin group (group R+S).Twenty healthy individuals served as control.The peripheral blood mononuclear cells (PBMCs) were isolated before and 4 weeks after the treatment and then cultured with interleukin-4 (IL-4) and granulocyte-macrophage colony stimulatory factor (GM-CSF) to prepare mature DCs.The expression of co-stimulating factor CD86 on the surface of DCs was assessed by flow cytometry.And the stimulating capacity of DCs was measured by mixed lymphocyte reaction (MLR).The contents of cytokines in culture supernatants of DCs in MLR were detected by ELISA.Blood lipids and high-sensitivity C-reactive protein (hs-CRP) were detected.The relationship between the expression of CD86 and the blood CRP level was also investigated.The results showed that,as compared with the control group,the CD86 expression and the level of cytokines secreted by DCs were significantly increased in RA patients and greater stimulating capacity of DCs in MLR was demonstrated in RA patients.T lymphocytes in MLR secreted higher levels of proinflammatory cytokines (IL-2,IL-17,TNF-α and INF-γ) and lower level of anti-inflammation cytokine (IL-10).The function of DCs was markedly weakened and the level of hs-CRP and low-density lipoprotein was substantially lowered in group R+S in comparison to group R.The CD86 expression was positively correlated with hs-CRP.It was concluded that DCs in RA are highly activated and DC-initiated immune reaction may play an important role in the pathogenesis of RA.Simvastatin administration can significantly inhibit the DCs function and reduce the level of hs-CRP,indicating the suppression on inflammatory reaction may be one of the mechanisms by which simvastatin exer     

Effects of therapeutic hypercapnia on inflammation and apoptosis after hepatic ischemia-reperfusion injury in rats

Background Therapeutic hypercapnia （TH） has been demonstrated to protect several organs ischemia-reperfusion injury.The study aimed to investigate the effects of therapeutic hypercapnia on hepatic ischemia-reperfusion injury （HIRI）.Methods Thirty adult male Wistar rats weighing （250 ± 20） g were randomized into 3 groups （n=10 in each）, group C （control group）, group A （hypercapnia group） and group B （CO2 preconditioning group）.A segmental ischemia of the liver was induced by interrupting the blood vessels including the bile duct to the median and left lateral lobes for 60 minutes and all the animals were sacrificed after 240 minutes observation period of reperfusion.Mean arterial pressure （MAP）and the blood gases were measured before ischemia （baseline） and at 30, 60, 120, 180 and 240 minutes after reperfusion.Arterial blood samples were obtained for determination of serum levels of TNF-α, IL-10, serum aspartate aminotransferase （AST） and alanine aminotransferase （ALT）.The histopathology of liver tissues was evaluated by light microscopy.The NF-κB expression and apoptotic hepatocytes were respectively determined by immunohistochemistry and TUNEL assay.Results The serum levels of liver enzymes and TNF-α were significantly decreased while the IL-10 level was significantly increased in groups A and B than in group C （P 〈0.05）, and group B surpassed group A （P 〈0.05）.The histopathological scores, the NF-κB immunohistochemical score （IHS） and apoptotic index were significantly lower in groups A and B than in group C （P 〈0.05）, and the decrease in group B was more obvious than in group A （P〈0.05）.Conclusion Therapeutic hypercapnia attenuates ischemia-reperfusion injury to the liver.Moreover, the effects of CO2preconditioning are outstandingly notable.