基于“微生物-肠-脑轴”探讨补肾通腑方对APP/PS1小鼠肠道菌群及LPS/TLR4/NF-κB通路的影响  

Effects of Bushen Tongfu Prescription on gut microbiota and LPS/TLR4/NF-κB pathway in APP/PS1 mice based on“microorganism-intestine-brain axis”

作　　者：王旭[1,2,3] 张杰 赵敏[1,3] 宋晓雨 段建平[1,2,3] WANG Xu;ZHANG Jie;ZHAO Min;SONG Xiao-yu;DUAN Jian-ping(Dept of Encephalopathy,the First Affiliated Hospital of Henan University of Chinese Medicine;the First Clinical Medical College,Henan University of Chinese Medicine,Zhengzhou 450000,China;Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine,Zhengzhou 450046,china)

机构地区：[1]河南中医药大学第一附属医院脑病科,河南郑州450000 [2]河南中医药大学第一临床医学院,河南郑州450000 [3]中西医防治重大疾病河南省协同创新中心,河南郑州450046

出　　处：《中国药理学通报》2025年第1期171-178,共8页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81904264);河南省中医药科学研究专项基金资助项目(No 2022JDZX004);河南中医药大学研究生科研创新能力提升计划(No 2023KYCX036);河南省高等学校重点科研项目(25B360020)。

摘　　要：目的探讨补肾通腑方调控肠道菌群,改善阿尔茨海默病(Alzheimer’s disease,AD)模型小鼠学习记忆能力的作用机制。方法以APP/PS1小鼠为研究对象,给予补肾通腑方治疗8周,采用Morris水迷宫法观察小鼠空间学习记忆能力变化;16S rDNA检测小鼠肠道菌群丰度、多样性变化;HE染色观察海马病理形态学变化;免疫荧光检测海马区小胶质细胞活化情况;Western blot检测TLR4、NF-κB、IL-6等炎症因子表达。结果与模型组相比,补肾通腑方可以缩短AD模型小鼠逃避潜伏期、游泳路径,增加跨越平台次数(P<0.05),提升肠道菌群多样性,调节肠道菌群丰度,促进海马神经元细胞损伤修复,降低iNOS/Iba1共表达,提高Arg1/Iba1共表达(P<0.01),促进小胶质细胞从M1型向M2型转化,下调TLR4、NF-κB、IL-6等促炎因子的表达。结论补肾通腑方改善AD模型小鼠学习记忆能力的作用机制可能与调节肠道菌群介导的LPS/TLR4/NF-κB通路,从而抑制促炎型小胶质细胞活化、减轻中枢神经系统炎症、改善海马区神经元细胞损伤有关。Aim To explore the mechanism of Bushen Tongfu prescription(BSTF)regulating gut microbiota and improving learning and memory ability of Alzheimer’s disease(AD)model mice.Methods APP/PS1 mice were administered by BSTF for eight weeks.The spatial learning and memory ability of mice were detected by Morris water maze.The changes in the gut microbiota abundance and diversity of mice were detected by 16S rDNA technology.The morphological changes of hippocampus were observed by HE staining.The expression of the activation of microglia in hippocampus was detected by immunofluorescence.The expressions of pro-inflammatory factors of TLR4,NF-κB and IL-6 in brain tissue were detected by Western blot.Results Compared with the model group,the escape latency and swimming path were shortened,the times of target crossings after removing the platform increased in BSTF groups(P<0.05),theα-diversity increased and the abundance of gut microbiota was regulated,the morphological structure and pathological damage of hippocampal cells were improved,the co-expression of iNOS/Iba1 decreased and the co-expression of Arg1/Iba1 increased significantly(P<0.01),the transformation of M1 to M2 of microglial cells was promoted,and the expression of TLR4,NF-κB and IL-6 protein decreased significantly.Conclusions BSTF can improve the learning and memory ability of APP/PS1 mice,and its mechanism may be related to regulating the gut microbiota and the LPS/TLR4/NF-κB pathway,inhibiting the activation of pro-inflammatory microglia,reducing inflammation in hippocampus and improving the pathological damage of hippocampal cells.

关 键 词：阿尔茨海默病 补肾通腑方 肠道菌群 LPS/TLR4/NF-κB通路 16S rDNA 微生物-肠-脑轴 

分 类 号：R285.5[医药卫生—中药学]