Triptolide inhibits inflammatory response and neuronal apoptosis in cerebral ischemia-reperfusion rats via JAK2/STAT3 pathway
Objective To investigate the effects of triptolide(TPL)on inflammation and neuronal apoptosis in rats with cerebral ischemia-reperfusion(CIR),and to explore its possible molecular mechanism.Methods A total of 192 SD rats were divided into sham operation group,model group,butylphthalide group,and low,medium and high dose TPL groups,with 32 rats in each group.The rat model of CIR was established by occlusion of the middle cerebral artery for 2 h.After reperfusion for 24 h,the neurological function,cerebral infarct volume and brain water content were measured;the pathological changes and neuronal apoptosis in the cortical neurons of the ischemic penumbra were observed;the levels of inflammatory factors in the ischemic cortex were measured by ELISA;the expressions of Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway proteins,high mobility group protein B1(HMGB1)and apoptosis-related proteins in the ischemic cortex were detected by Western blot.Results The middle and high dose TPL and butylphthalide significantly reduced the neurological deficit score,cerebral infarct volume and brain water content in CIR rats(P＜0.05);significantly improved the pathological changes of the cortical neurons in the ischemic penumbra and reduced the apoptosis rate(P＜0.05);reduced the levels of TNF-α and IL-1β in the ischemic cortex(P＜0.05),reduced the expression ratios of p-JAK2/JAK2,p-STAT3/STAT3,and Bax/Bcl-2,and the expression levels of HMGB1 and cleaved Caspase-3(P＜0.05).Except for the neurological deficit score and brain water content,the effects of high dose TPL on other indicators were better than butylphthalide(P＜0.05).Conclusion TPL may inhibit the inflammatory response and neuronal apoptosis in CIR rats by inhibiting the activation of JAK2/STAT3 pathway,and reduce the injury of CIR rats.
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