摘要
目的研究芦荟大黄素对阿尔茨海默病(Alzheimer's disease,AD)大鼠的神经保护作用以及可能的调控机制。方法选择健康雄性SD大鼠30只,采用随机分组的方式将大鼠分为空白组、模型组和芦荟大黄素组,每组10只。采用腹腔注射D-半乳糖和双侧颅内海马注射Aβ_(25-35)的方式联合进行AD大鼠模型的复制。芦荟大黄素组大鼠按10 mL/kg给予芦荟大黄素混悬液,空白组和模型组给予等容积纯水,共28 d。Morris水迷宫试验检测大鼠学习记忆能力,苏木精-伊红染色观察海马CA1区神经细胞损伤情况,Western blot法和qRT-PCR法分别检测大鼠海马磷脂酰肌醇3激酶(phosphatidylinositol-3-kinases,PI3K)/蛋白激酶B(protein kinase B,AKT)/哺乳动物雷帕霉素靶蛋白(the mammalian target of rapamycin,mTOR)通路蛋白、自噬相关蛋白及其mRNA的表达水平。结果AD大鼠学习记忆能力明显下降(P<0.05),海马CA1区神经细胞出现明显损伤,而芦荟大黄素可显著改善AD大鼠学习记忆能力(P<0.05),减轻海马CA1区神经细胞损伤;AD大鼠海马p-PI3K、p-AKT、p-mTOR、P62蛋白表达水平明显增加(P<0.05),Beclin-1和LC3Ⅱ/Ⅰ蛋白表达水平显著降低(P<0.05),而芦荟大黄素可以显著减少AD大鼠海马p-PI3K、p-AKT、p-mTOR、P62的蛋白表达水平(P<0.05),显著增加Beclin-1和LC3Ⅱ/Ⅰ蛋白表达水平(P<0.05);AD大鼠海马PI3K、AKT、mTOR、P62 mRNA表达水平显著增加(P<0.05),Beclin-1和LC3 mRNA表达水平显著降低(P<0.05),而芦荟大黄素可以显著减少大鼠海马PI3K、AKT、mTOR、P62 mRNA表达水平(P<0.05),显著增加Beclin-1和LC3 mRNA表达水平(P<0.05)。结论芦荟大黄素能够显著改善AD大鼠的学习记忆能力,其作用机制可能是通过调控PI3K/AKT/mTOR通路介导的自噬来实现的。
Objective To investigate the neuroprotective effect of aloe-emodin on rats with Alzheimer's disease(AD)and the possible regulatory mechanism.Methods A total of 30 healthy male Sprague-Dawley rats were selected and randomly divided into blank group,model group,and aloe-emodin group,with 10 rats in each group.A rat model of AD was established by the intraperitoneal injection of D-galactose combined with the bilateral hippocampal injection of Aβ_(25-35).The rats in the aloe-emodin group were given aloe-emodin suspension at a dose of 10 mL/kg,and those in the blank group and the model group were given an equal volume of pure water,for 28 days in total.Morris water maze was used to evaluate learning and memory abilities;HE staining was used to observe the injury of hippocampal CA1 neurons;Western blot and quantitative real-time PCR were used to measure the protein and mRNA expression levels of the PI3K/AKT/mTOR pathway proteins and autophagy-related proteins in the rat hippocampus.Results There were significant reductions in learning and memory abilities(P<0.05)and significant injuries of hippocampal CA1 neurons in AD rats,while aloe-emodin significantly improved the learning and memory abilities of AD rats(P<0.05)and alleviated the injury of hippocampal CA1 neurons.There were significant increases in the protein expression levels of p-PI3K,p-AKT,p-mTOR,and P62(P<0.05)and significant reductions in the protein expression levels of Beclin-1 and LC3 II/I(P<0.05)in the hippocampus of AD rats,while aloe-emodin significantly reduced the protein expression levels of p-PI3K,p-AKT,p-mTOR,and P62(P<0.05)and significantly increased the protein expression levels of Beclin-1 and LC3 II/I(P<0.05)in the hippocampus of AD rats.There were significant increases in the mRNA expression levels of PI3K,AKT,mTOR,and P62(P<0.05)and significant reductions in the mRNA expression levels of Beclin-1 and LC3(P<0.05)in the hippocampus of AD rats,while aloe-emodin significantly reduced the mRNA expression levels of PI3K,AKT,mTOR,and P62(P<0.05)and
作者
雷鑫
叶树
王国权
汪光云
宋航
蔡标
王艳
LEI Xin;YE Shu;WANG Guo-quan;WANG Guang-yun;SONG Hang;CAI Biao;WANG Yan(School of Integrated Traditional Chinese and Western Medicine, Anhui University of Chinese Medicine, Anhui Hefei 230012, China;Institute of Integrated Traditional Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Anhui Hefei 230012, China;Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui Hefei 230012, China;Key Laboratory of Chinese Medicinal Formula of Anhui Province, Anhui Hefei 230012, China)
出处
《安徽中医药大学学报》
CAS
2022年第3期71-78,共8页
Journal of Anhui University of Chinese Medicine
基金
国家自然科学基金项目(81873351)
安徽省杰出青年科学基金项目(1908085J27)
安徽高校自然科学研究项目(KJ2020A0439)。
