文献类型：期刊文献

中文题名：黑逍遥散调控p38MAPK/Beclin-1/Bcl-2通路对阿尔茨海默病模型大鼠自噬水平的影响

英文题名：Effect of Hei Xiaoyaosan regulating p38MAPK/Beclin-1/Bcl-2 pathway on autophagy level in Alzheimer's disease model rats

作者：王虎平[1,2];胡韵韵[1];吕育洁[1];孟志鹏[1];陈怡琴[1];杨娇[1]

第一作者：王虎平

机构：[1]甘肃中医药大学,甘肃兰州730000;[2]甘肃省中医方药挖掘与创新转化重点实验室甘肃省中药新产品创制工程实验室,甘肃兰州730000

第一机构：甘肃中医药大学

年份：2024

卷号：49

期号：12

起止页码：3348

中文期刊名：中国中药杂志

外文期刊名：China Journal of Chinese Materia Medica

收录：CSTPCD;;Scopus;北大核心:【北大核心2023】；CSCD:【CSCD2023_2024】；PubMed;

基金：国家自然科学基金项目(81960828,82160862);甘肃中医药大学科学研究与创新基金项目(2022KCZD-3);第五批全国中医临床优秀人才研修项目(国中医药人教函[2022]239号);首批陇原青年英才项目(中共甘肃省委人才工作领导小组[2022]5号)。

语种：中文

中文关键词：阿尔茨海默病;黑逍遥散;p38丝裂原活化蛋白激酶(p38MAPK);自噬水平

外文关键词：Alzheimer's disease;Hei Xiaoyaosan;p38 mitogen-activated protein kinase(p38MAPK);level of autophagy

摘要：探究黑逍遥散对阿尔茨海默病(Alzheimer′s disease, AD)自噬水平的影响。100只4月龄Wistar雄性大鼠,随机选取10只作为空白组,10只假手术组双侧海马注射1μL生理盐水,其余大鼠海马注射Aβ_(1-42)溶液复制AD模型,挑选造模成功大鼠50只,随机分为模型组、安理申组(0.5 mg·kg^(-1))及黑逍遥散高、中、低剂量组(15.30、7.65、3.82 g·kg^(-1)),每组10只,连续灌胃42 d。Morris水迷宫测试大鼠学习记忆能力,Hoechst染色观察海马CA1区神经细胞病理变化,RT-qPCR检测p38MAPK、Beclin-1、Bcl-2 mRNA表达,Western blot检测p38MAPK、Beclin-1、Bcl-2、APP及相关蛋白表达,ELISA法检测大鼠海马Aβ_(1-42)水平,免疫组化检测海马区LC3Ⅱ表达水平。实验结果显示,与空白组比较,模型组大鼠学习记忆能力下降(P<0.01),海马CA1区神经细胞核形态呈蓝色高亮斑,排列紧密,p38MAPK mRNA表达上调、Beclin-1 mRNA、Bcl-2 mRNA表达下调(P<0.01),p38MAPK、p-p38MAPK、APP表达增高,Beclin-1、Bcl-2、p-Bcl-2蛋白表达下降(P<0.01),Aβ_(1-42)表达增高(P<0.01),LC3Ⅱ相对表达下降(P<0.01)。与模型组比较,各给药组大鼠学习记忆能力改善(P<0.05或P<0.01),海马CA1区神经细胞核形态逐渐清晰,呈淡蓝色,p38MAPK mRNA表达下调(P<0.01),Beclin-1 mRNA、Bcl-2 mRNA表达提高(P<0.05或P<0.01),p38MAPK、p-p38MAPK、APP表达下调,Beclin-1、Bcl-2、p-Bcl-2蛋白表达上调(P<0.05或P<0.01),Aβ_(1-42)表达均下降(P<0.01),LC3Ⅱ相对表达上调(P<0.01)。由此可得,黑逍遥散可改善AD模型大鼠认知能力,其潜在机制可能与调控p38MAPK/Beclin-1/Bcl-2信号通路,提升自噬水平,减少Aβ_(1-42)积聚有关。
To explore the effect of Hei Xiaoyaosan on autophagy levels in Alzheimer's disease(AD).A total of 1004-month-old Wistar male rats were randomly selected as a blank group,and 10 rats were taken as a sham operation group and injected with 1μL of normal saline on both sides of the hippocampus.The other rats were injected with Aβ_(1-42) solution in the hippocampus to replicate the AD model.Fifty successfully modeled rats were selected and randomly divided into the model group,Aricatio group(0.5 mg·kg^(-1)),and high,medium,and low dose groups of Hei Xiaoyaosan(15.30,7.65,and 3.82 g·kg^(-1)),with 10 rats in each group.The rats were administered by continuous gavage for 42 days.Morris water maze was used to detect the learning and memory ability of rats,and Hoechst staining was used to observe the pathological changes of nerve cells in the hippocampal CA1 region.The mRNA expression of p38MAPK,Beclin-1,and Bcl-2 was detected by RT-qPCR.Western blot was used to detect the expressions of p38MAPK,Beclin-1,Bcl-2,APP,and related proteins.The level of Aβ_(1-42) in the hippocampus was detected by ELISA,and the expression level of LC3Ⅱin the hippocampus was detected by immunohistochemistry.The experimental results showed that compared with the blank group,the learning and memory ability of rats in the model group decreased(P<0.01).The nuclei in the CA1 region of the hippocampus showed blue bright spots and were closely arranged.The mRNA expression of p38MAPK was up-regulated,and the mRNA expressions of Beclin-1 and Bcl-2 were down-regulated(P<0.01).The expressions of p38MAPK,p-p38MAPK,and APP were increased,while those of Beclin-1,Bcl-2,and p-Bcl-2 were decreased(P<0.01).The expression of Aβ_(1-42) was increased(P<0.01).The relative expression of LC3Ⅱdecreased(P<0.01).Compared with the model group,the learning and memory ability of rats in each administration group was improved(P<0.05 or P<0.01).The nuclei in the CA1 region of the hippocampus gradually became clear,showing light blue.The mRNA expression of p38MAPK was down-regulated(P<0.01),and that of Beclin-1 and Bcl-2 was increased(P<0.05 or P<0.01).The expressions of p38MAPK,p-p38MAPK,and APP were down-regulated,while those of Beclin-1,Bcl-2,and p-Bcl-2 were up-regulated(P<0.05 or P<0.01).The expression of Aβ_(1-42) was decreased(P<0.01).The relative expression of LC3Ⅱwas increased(P<0.01).It can be concluded that Hei Xiaoyaosan can improve the cognitive ability of AD model rats,and its potential mechanism may be related to regulating the p38MAPK/Beclin-1/Bcl-2 signaling pathway,increasing the level of autophagy,and reducing the accumulation of Aβ_(1-42).