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Protective Effects And Mechanisms Of Salidroside Against Cerebral Ischemia-reperfusion Injury In Rat And LPS-induced Cellular Death In PC12

Posted on:2009-05-25Degree:MasterType:Thesis
Country:ChinaCandidate:X J ChenFull Text:PDF
GTID:2144360272458745Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
The role of inflammation and immune response following cerebral ischemia in brain ischemic injury has been widely investigated in the last decade.Salidroside,a novel extract of the chinese herb Crassulaceae has the activity of neuroprotection after cerebral ischemia-injury.However,the effects of salidroside on the inflammatory response and the expression of tumor necrosis factor-alpha(TNF-α) following cerebral ischemia remained unclear.The purposes of the present study were to evaluate the effects of salidroside on inflammation and the expression of TNF-αfollowing cerebral ischemia.Furthermore,we tested the effect of salidroside on LPS-induced cellular death in PC12 cells based on MTT assay.Part 1AIM To study the protective effects and the mechanisms of salidroside against cerebral ischemia-reperfusion injury in MCAO-I/R rats.METHEDS Focal cerebral ischemia in rats was produced by 1.5h occlusion of the middle cerebral artery(MCAO) and 24h reperfusion.Salidroside(5mg·kg-1) was administered intravenously immediately after occlusion and reperfusion respectively.The neurologic deficit score was investigated according to Zea-Longa's Standard.The infarct volume was assessed with software Image Pro 4.5 after TTC staining.The activities of MPO were estimated by test boxes produced by Nanjing Jiancheng Bioengineering Institute.The levels of TNF-αin central neutral system were measured by western blot.RESULTS Compared with the model group,salidroside treatment can significantly decrease the neurologic deficit score(P<0.05),reduce the moisture capacity(P<0.05) and the infarct volume(P<0.05).A significant increase in MPO activities was found in the salidroside treatment group,compared with the model control group(P<0.01).Also,salidroside treatment decreased the overexpression of TNF-α(P<0.05) in the brain. CONCLUSION Salidroside has a protective effect on cerebral ischemia-reperfusion injury and this effect is likely related to TNF-α. Part 2AIM To study the effect of salidroside on cellular death in lipopolysaccharide induced PC12 cells.METHEDS PC12 cells were treated with LPS or LPS plus salidroside.The viability of PC12 cells was measured using MTT assay.RESULTS Treatment of PC12 cells with LPS resulted in a significant inhibition(P<0.01) on the MTT assay(71.81%±4%,63.41%±6%,49.28%±4%and 4.84%±5%) when the normal control was defined as 100%.Compared with the model group,incubation for 24h with salidroside at concentrations at 0.6mg·L-1 and 6mg·L-1 resulted in a dose-related improvement in cell viability of PC12 cells cultured in RPMI1640 supplemented with 10%calf serum.CONCLUSION Salidroside exerted a neuroprotective property in PC12 cells.
Keywords/Search Tags:MCAO-I/R, Salidroside, MPO, TNF-α, PC12
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