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??OBJECTIVE To investigate the ameliorated effect and mechanisms of phenylethanoid glycosides from Pedicularis muscicola Maxim on high altitude memory impairment. METHODS After successfully trained in the 8-arms radial maze, fifty Wistar rats were randomly divided into normoxic control group, hypoxia group, phenylethanoid glycosides 50, 200 and 400 mg??kg^-1 groups(given corresponding dose). Normoxic control and hypoxia groups were administered with distilled water for a week.When drug delivery in the fourth day, hypoxia and phenylethanoid glycosides groups rats were exposed to a simulated of 7 500 m in a specially designed animal decompression chamber. Eight arms radial maze was used to measure spatial memory, HE stained was used to observe the cell morphology in brain tissue and biochemical technique was used to detect the content of MDA and ROS and enzymatic activity of GSH and SOD in brain tissue and serum. RESULTS Compared with the normoxic control group, for hypoxia group rats, WME, RWE and TE were respectively increased by 800%, 71%, and 127.1%(P??0.01) and neuron damage was significantly increased, the enzymatic activity of GSH and SOD were respectively decreased by 60.9% and 18.11%(P<0.05, P<0.01) in brain tissue and plasma while the content of MDA was increased in brain tissueby 74.8% (P<0.01). Compared with the hypoxia group, for phenylethanoid glycosides 200, 400 mg??kg^-1 groups rats, WME,RWE,TE were respectively decreased by 68.44%,63.11%;33.14%,25.34% and 43.91%, 36.72% (P??0.05, P??0.01) and neuron damage was significantly decreased, the enzymatic activity of GSH were respectively increased by 219.76%, 180.75% and 32.81%, 24.10% (P<0.05, P<0.01) and the enzymatic activity of SOD were respectively increased by 9.57%, 13.88% and 15.41%, 15.45% (P<0.05) in brain tissue and plasma,while the content of MDA in plasma were respectively decreased by 42.73%, 42.73% (P<0.01) and MDA and ROS in brain tissue were respectively decreased by 61.71%, 42.79% and 40.76%, 23.53% (P<0.01); for phenylethanoid glycosides 50 mg??kg^-1 group rats, the corresponding indicators had been ameliorated, but there was no significant difference.CONCLUSION Phenylethanoid glycosides of Pedicularis muscicola Maxim can ameliorate high altitude memory impairment, which its involved mechanism may be antioxidant stress and inhibition on cell damage.     

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??OBJECTIVE To observe the effect of guhong injection(GHI) on tibial fracture healing in rats and to explore the mechanism of the action of GHI. METHODS One hundred and eighty male SD rats were randomly divided into 6 groups with 30 rats in each group: sham operation group, model group, positive drug group(compound ossotide injection, 5 mL??kg^-1), low, medium and high dose of GHI groups(2.5, 5, 10 mL??kg^-1). In addition to the sham operation group, the other groups established the rat model of tibial fracture. All were given once daily intraperitoneal injections and samples were taken at 1st, 2nd, 4th and 6th week. Blood biochemical analysis and Elisa kit detection were performed on blood samples. X-rays, biomechanical tests, immunohistochemistry and RT-PCR were performed on the tibial samples. RESULTS ??After administration for one, two and four weeks, the levels of serum calcium(Ca) and phosphorus(P) in medium and high dose of GHI groups were higher than those in model group(P<0.05). ??X-ray showed that the outer callus growth and the disappearance of fracture line in all dose groups of GHI were faster than those in model group. ??Compared with model group, the maximum load and rigidity of medium and high dose of GHI groups were increased at each time point(P<0.05), and the trend of stress line graph were improved obviously. ??The content of alkaline phosphatase(ALP) in medium and high dose of GHI groups were higher than that in model group at each time point(P<0.05). Compared with model group, the serum levels of PDGF were increased in all dose groups of GHI(P<0.05 or P<0.01). After administration for one, two and four weeks, the serum BMP-2 in all dose groups of GHI were higher than those in model group(P<0.05 or P<0.01). ??Compared with model group, the expression of Runx2 mRNA were increased in medium and high dose of GHI groups, as well as Smad5 protein expression(P<0.05 or P<0.01). CONCLUSION GHI could significantly improve the biomechanical properties of bone in fracture rats. The promotion of fracture healing might be through the upregulation of PDGF and BMP-2 expression in different stages of bone healing, and the regulation of BMP/Smad5/ Runx2 signaling may be one of the mechanisms of promoting fracture healing.     

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??OBJECTIVE To investigate the effects of microwave radiation on learning and memory abilities in mice,and to study pilose antler peptide??s intervention. METHODS Fifty mice were divided into five groups randomly, designated as control group, radiation group, pilose antler peptide (25, 50, and 100 mg??kg^-1) groups. Learning and memory impairment model in mice was established by microwave radiation of 2 450 MHz average surface power, 10.0 mW??cm^-2 for 90 min every day for 28 d .The radiation rats were treated with low-, mid-, and high-dose (25, 50, and 100 mg??kg^-1) pilose antler peptide by sc injection for 28 d. The learning and memory ability of mice was determined by avoiding darkness experiment and Y maze experiment.The contents of S100B, tumor necrosis factor-??(TNF-??), interleukin-10(IL-10), malondialdehyde (MDA), and nitric oxide(NO) in the brain of mice were determined respectively after the behavioral experiments. RESULTS Compared with control group, radiation group could shorten the latency of avoiding darkness experiments, increase the numbers of errors both in avoiding darkness experiment and in Y maze experiment. Radiation group could rise the contents of S100B ,TNF-??, IL-10, MDA and NO in the brain of mice (P<0.05 or P<0.01). Compared with radiation group, pilose antler peptide (50, 100 mg??kg^-1) groups could lengthen the latency of avoiding darkness experiments, significantly shorten the numbers of errors both in avoiding darkness experiment and in Y maze experiment, and reduce the contents of S100B ,TNF-??, MDA and NO, increase the content of IL-10 in the brain of mice (P<0.05 or P<0.01). CONCLUSION Pilose antler peptide could significantly perfect the learning and memory ability of mice exposed to microwave radiation. The mechanism may be related to its anti-oxidative actions by anti-inflammatory action , further lowering neurotoxic effects of NO.     

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??OBJECTIVE To investigate the anti-depressant effect of schisandrin A in rats with depression caused by chronic unpredictable mild stress(CUMS)as well as the relevant mechanism. METHODS The depression-like rat model using CUMS was established. Rats were randomly divided into control, CUMS model, CUMS+fluoxetine (10 mg??kg^-1)and CUMS + schisandrin A (25, 50, 100 mg??kg^-1)groups. Drugs or vehicle were administrated after stress procedures for 21 d. Open-field test (OFT), sucrose preference tests (SPT)and forced swim test (FST)were used to evaluate the anti-depressant effects of schisandrin A. The reactive oxygen species (ROS)and prostaglandin E₂ (PGE₂) level as well as superoxide dismutase (SOD) and catalase (CAT)activities in hippocampus were determined by ELISA methods. IL-1??, TNF-??, and IL-10 expression were measured by real time qPCR and Western blot analysis. RESULTS Behavioral test indicated that crossing score and rearing score in OFT and sucrose preference index in SPT of model group were significantly lower than control group (P<0.01), while immobility time in FST was significantly increased (P<0.01). Compared with those in control group, the ROS and PGE₂ level increased significantly (P<0.01), SOD and CAT activities decreased significantly (P< 0.01),the mRNA and protein level of IL-1??, TNF-??, and IL-10 were increased significantly (P<0.05 or P<0.01)in rats of CUMS. CONCLUSION Schisandrin A and fluoxetine could ameliorate those changes induced by CUMS. Schisandrin A could improve the depression-like behaviors of rats induced by CUMS, of which the mechanism might involve the antioxidant and anti-inflammatory effects.     

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??OBJECTIVE To establish an HPLC-UV method for the simultaneous determination of valsartan and nifedipine in rats plasma, so as to study the pharmacokinetic interaction between valsartan and nifedipine and to provide useful information for clinical practice. METHODS Eighteen male Wistar rats were divided into three groups: valsartan group(16 mg??kg^-1), nifedipine group (4.2 mg??kg^-1) and combined group (containing valsartan 16 mg??kg^-1, nifedipine 4.2 mg??kg^-1). Plasma samples were collected at 0, 0.08, 0.16, 0.25, 0.5, 0.75, 1, 2, 4, 8, 10, 24 h after the drug administration. An HPLC with UV detection method was developed to determine the concentration of valsartan and nifedipine in rat plasma, and the pharmacokinetic parameters were calculated using non-compartment model. RESULTS Compared with single valsartan group, the pharmacokinetic parameters ??_max and AUC_0-t of the combined group had a significant increase(P<0.05), while Tmax and CLz/F had a significant decrease(P<0.05). Compared with single nifedipine group, the pharmacokinetic parameters t_1/2z/h had a significant decrease(P<0.05), while other pharmacokinetic parameters had no significant differences. CONCLUSION Combination of valsartan and nifedipine could significantly improve the valsartan in rats plasma concentration and bioavailability, increase absorption and decrease excretion , while nifedipine shows no pharmacokinetic change in rats except shortened half-life.     

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??OBJECTIVE To investigate the anti-depressant effect of icariin (Ica)in rats with depression caused by chronic unpredictable mild stress (CUMS) as well as the relevant mechanism. METHODS The depression-like rat model with chronic unpredicted mild stress was established. Rats were randomly divided into normal control, CUMS model, CUMS+Fluoxetine (10 mg??kg^-1) and CUMS + Ica(10, 20, 40 mg??kg^-1) groups. Drugs or vehicle were administrated after stress procedures for 21 d. Open-field test (OFT), sucrose preference tests (SPT)and forced swim test (FST) were used to evaluate the anti-depressant effects of Ica. The concentrations of the monoamine neurotransmitters including noradrenaline (NA), dopamine (DA), and 5-hydroxytryptamine (5-HT)in prefrontal cortex, hippocampus, and striatum were measured by HPLC-ECD. RESULTS Behavioral test indicated that crossing score and rearing score in OFT and sucrose preference index in SPT of model group were significantly lower than normal control group(P<0.01), while immobility time in FST was significantly increased (P<0.01). Compared with those in normal control group, the neurotransmitters including NA, DA and 5-HT were significantly decreased (P<0.01) in prefrontal cortex, hippocampus, and striatum in rats of CUMS. Ica and fluoxetine reversed those changes induced by CUMS. CONCLUSION Ica improves the depression-like behaviors of rats induced by CUMS, of which the mechanism might be increasing the contents of monoamine neurotransmitters including NA, DA and 5-HT.     

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??OBJECTIVE To abserve the antidepressant effect and mechanism of honokiol on acute and chronic stress mouse. METHODS Forced swimming model of acute stress (FST) and chronic stress mice model were used. The acute stress mouse were randomized into a control group, a fluoxetine group (3.3 mg??kg^-1), honokiol groups (2.5,5,10 mg??kg^-1). The chronic stress mouse were randomized into a blank group, a model group, a fluoxetine group(3.3 mg??kg^-1), honokiol groups (2.5,5,10 mg??kg^-1). Then, the immobility time of forced swimming, 5-hydroxytryptamine (5-HT) and 2,3- indole dioxygenase (IDO) contents in mouse brain tissue by Elisa Kit, and the expression of IDO mRNA in brain tissue used by quantitative real-time PCR were studied. RESULTS ??After acute stress, the immobility time of forced swimming in each treatment group was significantly shorter than that in the model group (P<0.05). The 5-HT content of fluoxetine and honokiol medium and high dose group was significantly higher than that of model group (P<0.05, P<0.01). The IDO content of honokiol high dose group was significantly higher than that of model group (P<0.05). ??After chronic stress, the immobility time of the model group were significantly higher than the blank group (P<0.01). The 5-HT content in brain tissue of the model group was significantly lower than that of the blank group (P<0.01), the IDO content in brain tissue and its expression level of mRNA increased comparing with the normal group (P<0.01). For each treatment group, the immobility time of forced swimming, IDO content and the expression level of IDO mRNA was significantly decreased, and the 5-HT content was significantly increased, comparing with the model group with significant difference (P<0.05). CONCLUSION Honokiol can relieve the depression behavior of mouse and have certain antidepressant effect. The main mechanism may be associated with the increase of 5-HT, reduction of the tryptophan pathway enzyme IDO content and its gene expression level.     

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??OBJECTIVE To explore the effects of luteolin on the proliferation and migration of the endothelial cells co-cultured with cancer cells and its molecular mechanism. METHODS Human umbilical vein endothelial cells (HUVECs) were primarily isolated and identified by the expression of VE-cadherin. Cancer-endothelial cell co-culture model was established using the Transwell system. The effects of luteolin at different concentrations (0 [Co-culture control], 20 and 50 ??mol??L^-1) on the proliferation and migration of HUVECs in the co-culture system were determined. A HUVECs control group removed of prostate cancer PC3 cells was also included. Human angiogenesis antibody array kit was used to assay the secretion levels of various protein factors in each group. RESULTS VE-cadherin was expressed on all the cultured HUVECs. Increased proliferation ability was found in the HUVECs co-cultured with PC3 cells compared with that in HUVECs control group (P<0.01). Treatment with 20 or 50 ??mol??L^-1 luteolin significantly inhibited the proliferation ability of the HUVECs in co-culture system (both P<0.01). Increased migration ability was found in the HUVECs co-cultured with PC3 cells compared with that in HUVECs control group (P<0.01). Treatment with 20 or 50 ??mol??L^-1 luteolin significantly inhibited the migration ability of the HUVECs in co-culture system (both P<0.01). Secretion levels of multiple angiogenesis-related proteins in the cultural supernatant of co-culture system were significantly increased compared with those in HUVECs control group. Treatment with 20 ??mol??L^-1 luteolin significantly inhibited the secretion levels of interleukin-8 (IL-8), vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1(MCP-1) in the cultural supernatant of co-culture system (all P<0.01). CONCLUSION Luteolin may inhibit the proliferation and migration of endothelial cells via suppressing the secretions of IL-8, VEGF and MCP-1 in cancer-endothelial co-culture system.     

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??OBJECTIVE To investigate the preliminary mechanism of no-ginsenoside small molecular component AFG(argininyl-fructoyl-glucose)in red ginseng to mice??s immune and anti-fatigue by forced swimming. METHODS Massive AFG was separated from red ginseng and was made powder(RM)by vacuum freeze drying machine. ICR mice were randomly divided into 4 groupsthe control group(CG),low dose group(RM-LG,100 mg??kg^-1),medium dose group(RM-MG,200 mg??kg^-1),high dose group(RM-HG, 400 mg??kg^-1), forced swimming test was made after continuous intragastric administration 28 d, and the mice??s weight was tested; organ index, time of forced swimming, volume of lactic acid(LD), urea nitrogen(BUN), hepatic glycogen(Gly), antioxidant enzyme in serum, ability of spleen lymphocyte proliferation,CD3,CD4,CD8 levels in spleen lymphocyte, releasing volume of immune factor were determined. RESULTS Compared with control group,weight and organ index of mice aren??t significant difference in treatment group; the force swimming time of treatment group is significantly increased(P<0.01);volume of LD,BUN and MDA in serum of treatment group are significantly reduced(P<0.01),volume of Gly,glutathione peroxidase(GSH-Px)and superoxide dismutase(SOD)in serum of treatment group are significantly increased(P<0.01);releasing volume of IL-2 and IgG in serum of treatment group are significantly increased(P<0.01); ability spleen lymphocyte proliferation and CD3, CD4, CD8 levels in spleen lymphocyte are significantly increased(P<0.05)at treatment group. CONCLUSION AFG has the effect of anti-fatigue and improving immunity in mice.