【摘 要】
:
目的:研究当归芍药散对β淀粉样蛋白1-42(Aβ1-42)诱导的阿尔茨海默病(AD)大鼠模型的神经保护作用及对NOD样受体3(NLRP3)/半胱氨酸天冬氨酸蛋白水解酶-1(Caspase-1)信号通路的调控作用.方法:大鼠脑内注射Aβ1-42构建AD动物模型,给予不同浓度的当归芍药散治疗.实验分为假手术组,模型组,当归芍药散高、中、低剂量干预组.Morris水迷宫实验检测动物学习记忆能力;苏木素-伊红(HE)染色和高尔基染色检测神经元形态功能;免疫荧光共定位检测NLRP3炎症小体活化情况;实时荧光定量聚合
【机 构】
:
湖南中医药大学中西医结合心脑疾病防治湖南省重点实验室,长沙410208
论文部分内容阅读
目的:研究当归芍药散对β淀粉样蛋白1-42(Aβ1-42)诱导的阿尔茨海默病(AD)大鼠模型的神经保护作用及对NOD样受体3(NLRP3)/半胱氨酸天冬氨酸蛋白水解酶-1(Caspase-1)信号通路的调控作用.方法:大鼠脑内注射Aβ1-42构建AD动物模型,给予不同浓度的当归芍药散治疗.实验分为假手术组,模型组,当归芍药散高、中、低剂量干预组.Morris水迷宫实验检测动物学习记忆能力;苏木素-伊红(HE)染色和高尔基染色检测神经元形态功能;免疫荧光共定位检测NLRP3炎症小体活化情况;实时荧光定量聚合酶链式反应(Real-time PCR)检测炎症因子白细胞介素-1β(IL-1β)和IL-18 mRNA表达情况;蛋白免疫印迹法(Western blot)检测NLRP3,Caspase-1,IL-1蛋白的表达水平.结果:与假手术组比较,模型组大鼠学习记忆能力显著降低(P<0.01);神经元形态功能受损;炎症因子IL-1β和IL-18 mRNA表达升高,NLRP3炎症小体活化增加,NLRP3,Caspase-1,IL-1β蛋白表达显著升高(P<0.01);与模型组比较,给予当归芍药散中、高剂量干预后,AD大鼠学习记忆能力明显增加(P<0.05,P<0.01);神经元形态功能明显恢复;炎症因子IL-1β和IL-18 mRNA表达显著降低,NLRP3炎症小体活化减少,NLRP3,Caspase-1,IL-1β蛋白表达显著降低(P<0.01).结论:当归芍药散可能通过调控NLRP3/Caspasc-1信号通路抑制炎症小体活化,抑制神经炎症反应,从而发挥神经保护作用.
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