黄芪甲苷Ⅳ通过激活PPAR-γ抑制NF-κB介导的炎症反应减少AD大鼠脑中淀粉样蛋白沉淀

AstragalosideⅣreduces Aβ_(1-42) protein expression in the brain of Alzheimer’s disease rats through PPAR-γactivation and inhibiting NF-κB-mediated inflammatio

目的探讨黄芪甲苷IV对阿尔茨海默病(AD)大鼠脑中β淀粉样蛋白和学习记忆功能的影响及其机制。方法将72只老年雄性SD大鼠随机分为6组,对照组、模型组、多奈哌齐组、黄芪甲苷低剂量组、黄芪甲苷高剂量组、黄芪甲苷高剂量+抑制剂组,每组12只。利用Aβ_(1-42)脑室注射与AlCl3连续灌胃建立AD模型,造模期间持续使用黄芪甲苷或多奈哌齐进行治疗,水迷宫结束后检测大脑组织中Aβ_(1-42)、APP及炎症因子表达,Western blot检测PPAR-γ及炎症相关蛋白表达。结果黄芪甲苷Ⅳ与多奈哌齐疗效一致,能够显著改善大鼠学习认知能力,抑制脑中APP水解成Aβ_(1-42),减少脑中炎症因子IL-1β、TNF-α、IL-6表达。黄芪甲苷Ⅳ能够有效升高PPAR-γ蛋白表达,减少NLRP3炎性小体的表达。此外,PPAR-γ抑制剂则逆转黄芪甲苷Ⅳ改善大鼠认知功能的作用,造成大鼠脑中炎症因子含量升高,促进APP水解生成Aβ_(1-42)。结论黄芪甲苷通过增加PPAR-γ蛋白表达,抑制大鼠脑中炎症因子表达,减少APP水解生成Aβ_(1-42),改善大鼠认知学习能力降低。

Objective To investigate the effect and mechanism of astragalosideⅣ(AS-Ⅳ)onβ-amyloid protein expression and cognitive function in the brain of rats with Alzheimer’s disease(AD).Methods 72 elderly male SD rats were randomly divided into 6 groups:Control group,Model group,Donepezil group,Low-dose AS-Ⅳgroup,High-dose AS-Ⅳgroup,High-dose AS-Ⅳ+GW9622 group,12 per group,Aβ_(1-42) and AlCl3 were used to establish AD models.In addition,AS-Ⅳand Donepezil were applied for AD treatments.The expression of Aβ_(1-42),APP and inflammatory factors in the brain tissue were measured through the kit,and PPAR-γand inflammatory protein were tested by Western blot.Results AS-Ⅳ,the same as donepezil,can significantly improve the cognitive ability in rats,inhibit the hydrolysis of APP into Aβ_(1-42),and reduce the expression of inflammatory factors like IL-1β,TNF-α,and IL-6.Meantime,AS-Ⅳcan effectively increase the expression of PPAR-γprotein and reduce the expression of NLRP3 inflammasome.In addition,PPAR-γinhibitors reversed the effect of AS-Ⅳon cognition improvement in rats,resulted in an increase in the levels of inflammasome and promoting the hydrolysis of APP to produce Aβ_(1-42).Conclusion AstragalosideⅣcan increase the expression of PPAR-γprotein,inhibit the expression of inflammasome,reduce the hydrolysis of APP into Aβ_(1-42,)and improve the cognitⅣe and learning ability of rats.