白藜芦醇通过RhoA/ROCK通路抑制缺血性脑卒中大鼠神经炎症OA

Objective:To investigate effects of resveratrol on cognitive impairment and neuroinflammation in ischemic stroke(IS)rats by regulating Ras homolog gene family member A(RhoA)/Rho kinase(ROCK)pathway.Methods:A total of 72 rats successfully modeled were divided into IS group,resveratrol group,RhoA activator(lysophosphatidic acid)group and resveratrol+lysophosphatidic acid group according to random number table method,with 18 rats in each group.Another 18 normal rats were selected as control group.Changes in neurological deficit score,number of platforms passed through,escape latency,and proportion of cere-bral infarction volume of rats were detected.Immunofluorescence staining was applied to detect number of ionized calcium-binding adapter molecule 1(Iba1)positive cells in brain tissue of hippocampal CA1 region.ELISA was applied to detect levels of TNF-α,monocyte chemoattractant protein-1(MCP-1)and IL-6 in brain tissue of hippocampal CA1 region.Western blot was applied to detect RhoA,ROCK1 and ROCK2 proteins in brain tissue of hippocampal CA1 region.Results:Compared with control group,number of platform crossing was decreased,escape latency prolonged,neurological dysfunction score,proportion of cerebral infarction volume,number of Iba1 positive cells in hippocampal CA1 brain tissue,levels of TNF-α,MCP-1,IL-6,RhoA,ROCK1 and ROCK2 proteins were increased in IS group(P<0.05).Compared with IS group,number of platform crossing was increased,escape latency shortened,neurological dysfunction score,proportion of cerebral infarction volume,number of Iba1 positive cells in hippocampal CA1 brain tissue,levels of TNF-α,MCP-1,IL-6,RhoA,ROCK1 and ROCK2 proteins were decreased in resveratrol group,trend of changes in corresponding indicators in lysophosphatidic acid group was opposite to resveratrol group(P<0.05).Compared with resveratrol group,number of platform crossing was decreased,escape latency prolonged,neurological dysfunction score,proportion of cerebral infarc-tion volume,number of Iba1 positive cells in hippocampal CA1 brain tissue,levels of TNF-α,MCP-1,IL-6,RhoA,ROCK1 and ROCK2 proteins were increased in resveratrol+lysophosphatidic acid group(P<0.05).Conclusion:Resveratrol may inhibit activation of microglia and neuroinflammation in IS rats by inhibiting RhoA/ROCK pathway,improving cognitive impairment.