滋补脾阴方药调节自噬增加内质网应激改善脾阴虚糖尿病认知功能障碍机制研究

Study of Zibu Piyin Recipe regulate autophagy and increase endoplasmic reticulum stress to improve spleen yin deficiency diabetes-associated cognitive decline

目的:观察LC3Ⅱ、抑制物阻抗性酯酶1α亚基(IRE1α)、c-Jun氨基端激酶(JNK)蛋白表达变化,探讨滋补脾阴方药调节自噬增加内质网应激(ERS)的作用机制。方法:将大鼠随机分为空白对照组(cont)、糖尿病组(DM)、脾阴虚组(pi)、脾阴虚糖尿病组(piDM)、滋补脾阴方药治疗组(ZBPYR)5组。采用Western Blot的方法观察LC3Ⅱ、IRE1α、JNK的蛋白表达变化。结果:DM组、pi组、piDM组大脑皮质LC3Ⅱ表达较cont组均降低(P<0.05),ZBPYR组LC3Ⅱ表达较DM组、piDM组升高(P<0.05)。DM组、pi组、piDM组大鼠大脑皮质p-IRE1α蛋白表达增加(P<0.05),DM组、piDM组大鼠大脑皮质p-JNK1以及p-JNK2较cont组均增加(P<0.05),ZBPYR组大鼠大脑皮质p-IRE1α、p-JNK1以及p-JNK2较DM组、piDM组降低(P<0.05)。结论:ZBPYR可通过调节自噬减轻ERS,改善糖尿病认知功能障碍。

Objective： The expression of LC3Ⅱ, inositol-requiring enzymeα（IRE1α）, c-Jun N-terminal kinase（JNK） were observed to explore the mechanism of Zibu Piyin Recipe（ZBPYR） on autophagy increasing endoplasmic reticulum stress（ERS）. Methods： The rats were randomly divided into five groups： cont group, DM group, pi group, piDM group and ZBPYR group. The expression of LC3Ⅱ, IRE1α, JNK were observed by western blotting. Results： The expression of LC3Ⅱ of DM group, pi group and piDM group decreased compared with cont group（P〈0.05）, the expression of LC3Ⅱ of ZBPYR group increased compared with DM group and piDM group（P〈0.05）. The IRE1α phosphorylation of DM group, pi group and piDM group increased compared with cont group（P〈0.05）, The phosphorylation of JNK1 and JNK2 of DM group, piDM group increased compared with cont group（P〈0.05）, ZBPYR decreased the phosphorylation of IRE1α, phosphorylation of JNK1 and JNK2 compared with DM group and piDM group（P〈0.05）. Conclusion： ZBPYR can reduce ERS through regulating autophagy to improve spleen Yin deficiency diabetes-associated cognitive decline.