摘要
目的探讨黄连解毒汤抑制APP/PS1小鼠内质网应激改善海马神经元损伤的作用机制。方法32只6月龄APP/PS1小鼠随机分为模型组、黄连解毒汤低、中及高组,每组8只。Morris水迷宫检测各组小鼠认知功能;原位末端转移酶标记(TUNEL)染色检测各组小鼠海马区神经元凋亡情况;免疫荧光染色检测小鼠海马区成熟神经元标记物NeuN表达情况;免疫组织化学染色检测小鼠海马区内质网应激标志分子GRP78、CHOP及Caspase-12蛋白表达;Western blot检测小鼠海马区XBP1、IRE1蛋白表达。结果与模型组相比,黄连解毒汤能明显缩短APP/PS1小鼠逃避潜伏期,增加小鼠穿越平台次数与目标象限停留时间;明显减少小鼠海马区神经元凋亡;明显增加小鼠海马区成熟神经元标记物NeuN表达;降低小鼠海马区GRP78、CHOP及Caspase-12蛋白表达;并且黄连解毒汤能够显著抑制小鼠海马区XBP1、IRE1蛋白表达。结论黄连解毒汤能够改善APP/PS1小鼠海马神经元损伤,其作用机制可能与调控IRE1-XBP1信号通路抑制内质网应激有关。
Objective To explore the mechanism of HuanglianJiedu Decoction inhibiting endoplasmic reticulum stress and improving hippocampal neuron injury in APP/PS1 mice.Methods Thirty-two 6-month-old APP/PS1mice were randomly divided into model group,low-,medium-and high-dose group of HuanglianJiedu Decoction,with 8mice in each group.The cognitive function of mice was detected by morris water maze.The apoptosis of neurons in the hippocampus of mice was detected by TUNEL staining.The expression of NeuN in the hippocampus of mice was observed by immunofluorescence staining.The expression of GRP78,CHOP and Caspase-12 in the hippocampus of mice was observed by immunohistochemical staining.The expression of XBP1 and IRE1 in the hippocampus of mice was detected by Western blot.Results Compared with the model group,HuanglianJiedu Decoction can significantly shortened the escape latency of APP/PS1 mice,and increased the number of platform crossing and target quadrant residence time of mice,reduce the number of apoptotic neuron in the hippocampus,increase the expression of NeuN in the hippocampus of the mice,reduce the expression of GRP78,CHOP and Caspase-12 in the hippocampus of mice,and inhibit the expression of XBP1 and IRE1.Conclusion HuanglianJiedu Decoction can improve hippocampal neuron damage in APP/PS1 mice,and its mechanism may be related to the regulation of IRE1-XBP1 signaling pathway to inhibit endoplasmic reticulum stress.
作者
柴学森
王振川
李莹
王猛
CHAI Xue-sen;WANG Zhen-chuan;LI Ying;WANG Meng(Department of Neurology,Fushun Hospital of Traditional Chinese Medicine,Fushun 113008;Department of Neurology,Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110034,China)
出处
《解剖科学进展》
CAS
2022年第6期657-661,共5页
Progress of Anatomical Sciences
基金
辽宁省自然科学基金(20180551041)
