基于ACE2-Ang(1-7)-Mas轴研究参芪地黄汤对2型糖尿病模型大鼠认知功能的影响  

Effects of Shenqi Dihuang Decoction on cognitive function in rats with type 2 diabetes mellitus model based on ACE2⁃Ang(1⁃7)⁃Mas axis

作　　者：齐雅芝 李君[1] 唐娅 曹睿 翟燕玲 徐强[1] 韩玉生[1] QI Yazhi;LI Jun;TANG Ya;CAO Rui;ZHAI Yanling;XU Qiang;HAN Yusheng(Heilongjiang University of Chinese Medicine,Heilongjiang Harbin 150040;Jiamusi Campus of Heilongjiang University of Chinese Medicine,Heilongjiang Jiamusi 154007)

机构地区：[1]黑龙江中医药大学,黑龙江哈尔滨150040 [2]黑龙江中医药大学佳木斯学院,黑龙江佳木斯154007

出　　处：《海南医学院学报》2024年第21期1625-1633,共9页Journal of Hainan Medical University

基　　金：国家自然科学基金面上项目(82074530)。

摘　　要：目的:观察参芪地黄汤对2型糖尿病(T2DM)认知障碍的改善作用,通过对ACE2-Ang-(1-7)-Mas轴的研究进一步探讨参芪地黄汤改善糖尿病认知功能障碍的可能机制。方法:24只雄性SD大鼠采用高脂高糖饲料喂养联合链脲佐菌素(STZ)腹腔注射构建T2DM大鼠模型,随机分为模型组和参芪地黄汤低、中、高剂量组,每组6只,另设6只为空白对照组。给药组灌胃相应剂量药物(低中高剂量分别为10.8、21.6、32.4 g/kg)连续8周。Morris水迷宫实验观察大鼠行为学变化;HE染色观察大鼠海马组织的病理学改变;ELISA检测大鼠血清中胰岛素含量,海马中血管紧张素(1-7)[Ang(1-7)],白细胞介素1β(IL-1β),白细胞介素18(IL-18)和肿瘤坏死因子-α(TNF-α)的含量;免疫组化,Western blot检测海马中血管紧张素Ⅱ(AngⅡ)、血管紧张素转换酶2(ACE2)、Mas受体(MasR)、NOD样受体蛋白3(NLRP3)、半胱氨酸天冬酶-1(Caspase-1)蛋白。结果:与对照组比较,模型组空腹血糖水平升高;大鼠平均逃避潜伏时间显著延长,而穿越平台的次数则显著减少(P<0.01);海马组织结构疏松,炎细胞浸润明显,小胶质细胞显著增多。与模型组比较,各给药组空腹血糖水平均降低,胰岛素水平均升高;参芪地黄汤中、高剂量组大鼠潜伏期显著缩短,穿越平台次数显著增多(P<0.05);大鼠神经元结构较完整,炎细胞浸润、小胶质细胞显著减少。与对照组比较,模型组组织中Ang-(1-7)和IL-1β、IL-18和TNF-α等细胞因子水平显著上升(P<0.01),海马中ACE2、Mas表达显著下降(P<0.05),而AngⅡ、NLRP3、Caspase-1表达则显著上升(P<0.05);与模型组相比,经过给药后各组海马中AngⅡ、NLRP3、Caspase-1表达显著下降(P<0.05),ACE2、Mas则显著升高(P<0.05)。结论:参芪地黄汤可能通过调节ACE2-Ang-(1-7)-Mas轴抑制NLRP3炎性小体的激活,减少炎症级联反应从而改善T2DM模型大鼠认知功能障碍。Objective:To observe the effect of Shenqi Dihuang Decoction on cognitive impairment in type 2 diabetes mellitus(T2DM)rats,and to delve deeper into understanding how Shenqi Dihuang Decoction may ameliorate cognitive impairment in diabetes mellitus,we aim to investigate its potential mechanism by studying the ACE2-Ang-(1-7)-Mas axis.Methods:Twenty-four male Sprague-Dawley rats underwent high-energy and abdominal streptomycin injections to induce type 2 diabetes mellitus(T2DM)rat models.They were then randomly allocated into the model group and three Shenqi Dihuang Decoction dosage groups(low,medium,and high),each containing six rats,with an additional six rats in the control group.The drug groups were gavaged with the corresponding doses of Shenqi Dihuang Decoction(10.8,21.6 and 32.4 g/kg for low,medium and high doses,respectively)for 8 consecutive weeks.Morris water maze experiments observing behavioral changes in rats and pathological changes in the hippocampus tissues were observed by HE staining;insulin content in serum,Ang(1-7),IL-1β,IL-18 and TNF-αlevels in hippocampus were detected by ELISA;Western blot detected AngII,ACE2,MasR,NLRP3,and Caspase-1 proteins were deter mined by western blot method.Results:Compared with the control group,the fasting blood glucose level increased in the model group;The latenly period of rats has increased significantly but times of rats going through the platforms has decreased significantly.(P<0.05);the hippocampal tissue structure was sparse,with obvious infiltration of inflammatory cells,and number of microglial cells significantly increased.Compared with the model group,fasting blood glucose levels were reduced and insulin levels were increased in all treatment groups;Rats in the middle and high dosage groups of Shenqi Dihuang Decoction exhibited significantly reduced latency periods,along with a notable increase in the number of times they crossed the platform(P<0.05);The neuronal structure of rats appeared more preserved,showing reduced infiltration of inflammatory cells

关 键 词：2型糖尿病 认知功能障碍 参芪地黄汤 ACE2-Ang-(1-7)-Mas 

分 类 号：R285.5[医药卫生—中药学]