ERB-041通过ERβ/NLRP3信号通路对阿尔兹海默症的保护作用

The protective effect of ERB-041 on Alzheimer′s disease via ERβ/NLRP3 signaling pathway

目的探究ERB-041对阿尔兹海默症小鼠的保护作用及可能机制。方法以野生型C57BL/6小鼠作为对照组(Control组),APP/PS1双转基因小鼠随机分为阿尔兹海默症组(AD组)和ERB-041组,每组10只。水迷宫实验检测小鼠空间学习记忆能力;免疫荧光检测小鼠海马组织Aβ蛋白表达;HE染色观察小鼠海马组织病理学变化;TUNEL实验检测小鼠海马组织细胞凋亡;Western blot检测小鼠海马组织ERβ、Bax、cleaved-caspase3、Bcl-2、NLRP3和cleaved-caspase1蛋白表达水平。结果ERB-041降低阿尔兹海默症小鼠逃避潜伏期,增加小鼠穿越平台次数和目标象限停留时间,降低小鼠海马组织TUNEL阳性细胞数和Aβ、Bax、cleaved-caspase3、NLRP3和cleaved-caspase1蛋白表达水平,增加小鼠海马组织Bcl-2和ERβ蛋白表达水平。结论ERB-041改善AD小鼠的作用与激活ERβ/NLRP3信号通路相关。

Objective To explore the protective effect and its possible mechanism of ERB-041 on Alzheimer′s disease mice.Methods Wild type C57BL/6 mice were used as control group,and APP/PS1 double transgenic mice were randomly divided into Alzheimer′s disease group(AD)and ERB-041 group,with 10 mice in each group.Water maze test was used to test the spatial learning and memory ability of mice.The expression of Aβin mouse hippocampus was detected by immunofluorescence.The histopathological changes of mice hippocampus were observed by HE staining.TUNEL assay was used to detect the apoptosis of hippocampal cells.The expressions of ERβ,Bax,cleaved caspase3,Bcl-2,NLRP3,and cleaved caspase1 in the hippocampus of mice were detected by Western blot.Results ERB-041 decreased the escape latency of AD mice,increased the number of platform crossing and target quadric residence time,decreased the number of TUNEL positive cells and the expressions of Aβ,Bax,cleaved caspase3,NLRP3 and cleaved caspase1 in the hippocampus of mice,increased the expressions of Bcl-2 and ER-βin mouse hippocampus.Conclusion The improved effect of ERB-041 on AD mice is related to the activation of ERβ/NLRP3 signaling pathway.