洗心汤对D-半乳糖联合Aβ_(25-35)致AD模型大鼠脑肠区NGF相关蛋白及肠道菌群的影响  

Effects of Xixin Decoction on NGF related proteins and intestinal flora in the gut-brain region of compound AD rats

作　　者：王登坤 第五永长[2] 苟于瑞 王威 熊鹏 周源 刘奇[2] WANG Deng-kun;DI Wu-Yongchang;GOU Yu-rui;WANG Wei;XIONG Peng;ZHOU Yuan;LIU Qi(Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine,Xiangyang Shaanxi 712099 China;Shaanxi University of Traditional Chinese Medicine,Xianyang Shaanxi 712046,China;Ankang Traditional Chinese Medicine Hospital,Ankang Shaanxi 725000,China;940th Hospital of Joint Logistics Support Force of PLA,Lanzhou Gansu 730050,China)

机构地区：[1]陕西中医药大学附属医院,陕西咸阳712099 [2]陕西中医药大学,陕西咸阳712046 [3]安康市中医医院,陕西安康725000 [4]中国人民解放军联勤保障部队第九四〇医院,甘肃兰州730050

出　　处：《时珍国医国药》2023年第11期2624-2628,共5页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金面上项目(82074503);陕西中医药大学神经退行性疾病中医药防治研究学科创新团队项目(2019-QN05);陕西省“特支计划”科技创新领军人才项目(陕组通字【2018】33号)。

摘　　要：目的研究洗心汤对复合型阿尔茨海默病(AD)大鼠肠道菌群及脑肠区NGF相关蛋白的影响,初步探讨洗心汤通过微生物-肠-脑轴防治AD的作用机制。方法采用D-半乳糖(D-Gal)腹腔注射联合双侧脑室注射Aβ_(25-35)建立复合型AD模型大鼠。末次灌胃结束后采用Morris水迷宫检测记忆认知功能;HE染色观察脑组织病理改变;免疫组化法检测脑组织Aβ_(1-42)蛋白阳性表达情况;蛋白免疫印迹法检测海马中NGF、TrkA及结肠中NGF蛋白表达;16S rRNA检测肠道菌群多样性及属水平上菌群分布情况。结果与AD组比较,洗心汤组大鼠逃避潜伏期、脑内Aβ_(1-42)蛋白阳性表达情况均改善,海马NGF、TrkA及结肠NGF蛋白表达均增加(P<0.05,P<0.01);16S rRNA结果显示,洗心汤组大鼠肠道微生物Chao1、Ace指数较于AD组均上升,且大肠埃希菌-志贺菌属、异杆菌属相对丰度降低,而帕拉普氏菌属相对丰度增加(P<0.05)。结论洗心汤可能增加肠道菌群多样性,并对菌群分布有一定的调控作用,可调控脑肠区NGF相关蛋白的合成与分泌,进而改善AD大鼠记忆认知功能及一定程度上逆转AD典型病理特征。Objective To study the effects of Xixin Decoction on the intestinal flora and NGF-related proteins in the brain-gut region of rats with complex Alzheimer's disease(AD),and to preliminarily explore the mechanism of Xixin Decoction in preventing and treating AD through the microbe-gut-brain axis.Methods Compound AD model rats were established by intraperitoneal injection of D-galactose(D-Gal)combined with bilateral intraventricular injection of Aβ_(25-35).After the last intragastric administration,Morris water maze was used to detect memory and cognitive function;HE staining was used to observe the pathological changes of brain tissue;immunohistochemical method was used to detect the positive expression of Aβ_(1-42) protein in brain tissue;Western blot was used to detect NGF,TrkA and colon in hippocampus.16S rRNA was used to detect the diversity of intestinal flora and the distribution of flora at the genus level.Results Compared with the AD group,the escape latency and the positive expression of Aβ_(1-42) protein in the brain of the rats in the Xixin decoction group were improved,and the expressions of NGF,TrkA and colon NGF proteins in the hippocampus were increased(P<0.05,P<0.01);16S rRNA The results showed that the Chao1,Ace indexes of intestinal microbes in the Xixin decoction group were all increased compared with those in the AD group,and the relative abundances of Escherichia coli-Shigella and Isobacterium were decreased,while the relative abundance of Parapusella was decreased.The relative abundance increased(P<0.05).Conclusion Xixin decoction may increase the diversity of intestinal flora,and has a certain regulatory effect on the distribution of flora,which can regulate the synthesis and secretion of NGF-related proteins in the brain-gut region,thereby improving memory and cognitive function in AD rats and to a certain extent.Reversal of pathological features of AD.

关 键 词：阿尔茨海默病 洗心汤 NGF/TrkA 肠道菌群 肠-脑轴 

分 类 号：R285.5[医药卫生—中药学]