Effects Of Astragaloside Ⅳ Combined With Active Components Of Panax Notoginseng On Apoptosis And Endoplasmic Reticulum Stress In Brain Tissues After Cerebral Ischemia-reperfusion In Mice

Objective:To probe the effects and mechanisms of astragaloside IV combined with the effective components of Panax notoginseng on apoptosis of nerve cells through endoplasmic reticulum stress (ERS) after cerebral ischemia-reperfusion in mice.Methods:C57BL/6mice were randomly divided into:sham, model, Astragaloside Ⅳ (AST Ⅳ), Ginsenoside Rg1(Rg1), Ginsenoside Rb1(Rb1), Notoginsenoside R1(R1), four active components combination, AST Ⅳ+Rg1, AST Ⅳ+Rb1, AST Ⅳ+R1and Edaravone, pretreated for3d. After1h of the last administration, the model of cerebral ischemic-reperfusion injury was established by bilateral common carotid artery (CCA) ligation followed by reperfusion, then TUNEL method was used to detect apoptosis in hippocampal CA1and apoptosis rate was calculated, expressions of cysteine aspartic acid specific protease (caspase-3)、glucose regulated protein78(GRP78^caspase-12and phosphorylated C-Jun amino terminal enzyme (p-JNK) proteins in brain tissues were test by western-blot at24h after reperfusion.Results:1. After cerebral ischemia for20min followed by reperfusion24h, the apoptosis rate of never cell in hippocampal CA1and the expression of caspase-3protein in brain tissues were increased. All drugs could decrease the apoptosis rate, inhibit caspase-3protein expression. Furthermore, the decreased effects of AST Ⅳ+Rgl and AST Ⅳ+R1on the apoptosis rate and caspase-3protein expression were better than those of the active components alone; In four active components combination, the decrease of the apoptosis rate was stronger than that of four active components alone and AST Ⅳ+Rb1, the inhibition of caspase-3was greater than that of four active components alone and AST Ⅳ+Rb1, AST Ⅳ,+R1.2. After cerebral ischemia-reperfusion, the expression of GRP78and caspase-12, p-JNK proteins were up-regulated. AST Ⅳ, Rg1,R1and the combinations could further increase GRP78protein expression in brain tissues, and the effect of the combinations was better than that of the active components alone, the effect of four active components combination was better than that of AST Ⅳ+Rb1, and AST Ⅳ+R1. R1, four active components combination, AST Ⅳ+Rgl, AST Ⅳ+R1could down-regulate caspase-12protein, the effect of four active components combination was more obvious than that of four active components alone and AST Ⅳ+Rb1. The expression of p-JNK in AST Ⅳ, Rg1, four active components combination, AST Ⅳ+Rg1, AST Ⅳ+Rb1was decreased, the decrease in four active components combination was stronger than that in four active components alone and AST Ⅳ+Rg1, AST Ⅳ+R1.Conclusion:AST Ⅳ combined with the effective components of Panax notoginseng had the potentiation on the inhibition of apoptosis, the mechanism underlying might be associated with relieving ERS via different links. AST Ⅳ+Rb1might affect JNK pathway, AST Ⅳ+R1might act on the caspase-12pathway, moreover, four active components combination and AST Ⅳ+Rg1could act on both caspase-12and JNK.