基于RhoA/ROCK2通路探讨七味白术散对糖尿病脑病大鼠学习记忆与突触可塑性的影响  

Exploring the effects of Qiwei Baizhu San on learning memory and synaptic plasticity in Wistar rats with diabetic encephalopathy based on the RhoA/ROCK2 pathway

作　　者：尹怡然 冯晓帆[1] 高佳馨 王建波[1] 张云雨 郑一[1] 于海航 YIN Yi-ran;FENG Xiao-fan;GAO Jia-xin;WANG Jian-bo;ZHANG Yun-yu;ZHENG Yi;YU Hai-hang(Liaoning Universicty of Traditional Chinese Medicine,Shenyang Liaoning 110847,China;Hebei University of Engineering,Handan Hebei 056038,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]河北工程大学,河北邯郸056038

出　　处：《时珍国医国药》2024年第1期56-59,共4页Lishizhen Medicine and Materia Medica Research

基　　金：辽宁省自然科学基金(2019-ZD-0954)。

摘　　要：目的 探讨七味白术散对糖尿病模型大鼠海马组织RhoA/ROCK2通路的作用,并探讨其改善糖尿病脑病的作用机制。方法 以高脂饲料结合STZ复制并筛选出符合条件的DE大鼠模型,随机分为模型组、七味白术散低、中、高剂量组、西药组。另设不造模的正常组。采用Morris水迷宫实验观察各组大鼠学习和空间记忆能力,用ELISA法检测海马组织中β-淀粉样蛋白42(β-amyloid protein 42,Aβ42)与磷酸化Tau蛋白(p-tau)含量,用RT-PCR法和Western blot检测海马样本中突触相关蛋白Syn、突触后致密物质PSD95(Postsynaptic density protein-95,PSD95)、RhoA、ROCK2的表达水平。结果 在检测各海马样本中Syn、PSD95、RhoA及ROCK2相对表达后,发现七味白术散干预4周后,模型组与正常组比较:RhoA、ROCK2表达水平显著升高,Syn、PSD95表达水平显著下降,差异有统计学意义(P<0.01),提示DE大鼠海马组织中的RhoA/ROCK2信号通路被抑制。中剂量组与模型组比较后发现:RhoA、ROCK2表达水平显著下降,Syn、PSD95表达水平显著上升,差异有统计学意义(P<0.01),表明七味白术散可能通过抑制RhoA/ROCK2通路,并调节突触可塑性。结论 七味白术散可能是通过抑制RhoA/ROCK2信号通路并上调突触可塑性来改善患有DE的大鼠。Objective To investigate the effect of Qiwei Baizhu San on the RhoA/ROCK2 pathway in rats with diabetes mellitus model and to explore its effect on improving diabetic encephalopathy.Methods A high-fat diet combined with STZ was used to replicate and screen the eligible DE rat model,which was randomly divided into,a model group,a western medicine group and high,medium,and low-dose Qiwei Baizhu San groups,and Set up a normal control proup without modeling.Observe the changes in blood glucose and body mass in each group of rats.The Morris water maze experiment was used to examine the learning and each set of spatial memory abilities of rats.Determination of Aβ42 and p-tau in hippocampal tissue by ELISA.The expression levels of synaptic-related protein Syn,postsynaptic density protein-95(PSD95),RhoA and ROCK2 in hippocampal samples were measured by RT-PCR and Western blot.Results In this study,when the relative expression of Syn,PSD95,RhoA and ROCK2 proteins in each hippocampal sample was examined,it was found that after 4 weeks of drug treatment,the expression levels of RhoA and ROCK2 increased significantly in the model group compared with the control group,and the expression levels of Syn and PSD95 decreased significantly,with statistically significant differences(P<0.01),suggesting that the hippocampal tissue of DE rats RhoA/ROCK2 signaling pathway was inhibited in hippocampal tissues of DE rats.After comparing the medium dose group of QiWei BaiZhu San with the model group,it was found that the expression levels of RhoA and ROCK2 decreased significantly,while the expression levels of Syn and PSD95 increased significantly,and the difference was statistically significant(P<0.01),indicating that QiWei BaiZhu San may inhibit the RhoA/ROCK2 pathway and regulate synaptic plasticity.Conclusion Qiwei Bai⁃jusan can inhibit the RhoA/ROCK2 signaling pathway to improve DE in rats with DE,and the mechanism of action may also be re⁃lated to synaptic-related proteins.

关 键 词：糖尿病脑病 RhoA/ROCK2通路 突触可塑性 七味白术散 

分 类 号：R285.5[医药卫生—中药学]