To Investigate The Neuroprotective Effect And Mechanism Of Huoxue Rongluo Recipe On Cerebral Ischemia-reperfusion Injury Rat Model Based On SIRT1/PGC-1? Pathway

Objective: To study the influence of Huoxue Rongluo on SIRT1/PGC-1 ? signal route after encephalic ischemia-reperfusion damage in rats,and to search its sheltered mechanism on neurons in rats with encephalic ischemia-reperfusion damage.Methods: 60 SD healthy male rats were divided into fake surgery group stochastically,model group,model + Huoxue Rongluo recipel group,model + EX-527 group,model+ EX-527+ Huoxue Rongluo recipel group and model + idi benzoquinone group with10 rats in each group.The model of focal encephalic ischemia-reperfusion in rats was established by thread occlusion method.(MCAO),fake surgery group only separated blood vessels without thread occlusion,and each drug group was given intragastric administration of corresponding drugs(10ml kg-1)at 36 h,12 h and 12 h before model establishment,respectively.Use gavage to deal with the fake surgery group and model group,give same potion distilled water,Score of neurological deficit 24 h after reperfusion.The pathomorphological changes of encephalic cortex were observed by HE staining,the content of ATP in cortical brain was measured by kit,RT-q PCR measure the expression of SIRT1 m RNA and PGC-1 ? m RNA in cortical brain,and immunohistochemistry measure the expression of SIRT1 and PGC-1 ? in cortical brain.Results: 1.Coloboma of neurological effect score: Compared with the fake surgery group,the model group of neurological deficit score was obvious rised.Compared with the model group,the neurological deficit score in Huoxue Rongluo group and idi benzoquinone group was significantly lower than that in Huoxue Rongluo recipel group.The neurological deficit score of EX-527 group was obvious higher than that Huoxue Rongluo prescription group.The neurological deficit score was obvious increased in Huoxue Rongluo + EX-527 group.The neurological deficit score was significantly increased in Huoxue Rongluo + EX-527 group,but irdibenone group and Huoxue Rongluo recipe group Compare the differences is no sense in statistics(P >0.05).2.HE staining: fake operation group: normal morphology,orderly arrangement and clear structure of cortical neurons around ischemia in rats;model group: decrease in number of cortical neurons,uneven chromatin,disordered arrangement,widening of pericellular space and nuclear pyknosis in model group.Compared with the model group,the damage of neurons in Huoxue Rongluo group and idi benzoquinone group was alleviated,the cell morphology and structure was more complete,and the intracellular vacuolation decreased,while in EX-527 group,the neuronal damage was aggravated,the cells were obviously vacuolated,disordered and nuclear pyknosis was obvious.Compared with Huoxue Rongluo group,the arrangement of cells in Huoxue Rongluo + EX-527 group was more disordered,and the vacuolation,nuclear pyknosis and nucleolysis were increased.3.ATP content: ATP content in the ischemic cortex of the model group decreased obvious than fake operation group,compared with the model group,the ATP content of ischemic cortex increased significantly in the Huoxue Rongluo recipel group and idi benzoquinone group,and the ATP content decreased significantly in the EX-527group(P < 0.05).Compared with Huoxue Rongluo,the content of ATP in brain tissue decreased significantly in Huoxue Rongluo+EX-527 group,but there was no significant difference in ATP content in encephalic ischemic cortex between aidibenone group and Huoxue Rongluo group(P > 0.05).4.SIRT1 m RNA q PCR: compared with the fake surgery group,the expression levels of SIRT1 m RNA and PGC-1? m RNA in the ischemic cortex of the model group were obviously reduced,while the expression levels of SIRT1 m RNA and PGC-1? m RNA in the ischemic cortex of the Huoxue Rongluo group and idibenzoquinone group were significantly higher than those of the model group,while the expression levels of SIRT1 m RNA and PGC-1 ? m RNA in the Adibenone group were obviously higher than the model group,while the express levels of SIRT1 m RNA and PGC-1? m RNA in the Adibenone group were obviously lower than model group.Compared with Huoxue Rongluo group,the expression levels of SIRT1 m RNA and PGC-1? m RNA reduced obviously in Huoxue Rongluo + EX-527 group,but SIRT1 m RNA and PGC-1? m RNA expression levels has no obviously difference levels in encephalic ischemic cortex between aidibenone group and Huoxue Rongluo group(P > 0.05).5.Immunohistochemistry: compared with the fake operation group,the expression of SIRT1 and PGC-1? in the ischemic cortex of the model group reduced obviously,compared with the model group,the expression of SIRT1 and PGC-1? increased obviously in the Huoxue Rongluo group and idi benzoquinone group,while the expression of SIRT1 and PGC-1? reduced obviously in the EX-527 group.Compared with the Huoxue Rongluo group,the expression of SIRT1 and PGC-1? in the Huoxue Rongluo + EX-527 group decreased significantly,but there was no significant difference in the expression of SIRT1 and PGC-1? in the encephalic ischemic cortex between the aidibenone group and the Huoxue Rongluo group.Conclusion: 1.Huoxue Rongluo can effectively improve the symptoms of neurological deficit in the rat model of encephalic ischemia-reperfusion damage,regulate the level of mitochondrial energy metabolism and promote the recovery of neurological function.2.Huoxue Rongluo may play a sheltered role on neurons by activating SIRT1/PGC-1 ? signal route,promoting the expression of SIRT1 and PGC-1 ? and increasing the level of ATP.