化浊解毒疏肝方通过调控SIRT1/PGC-1α/PPARγ通路对血管性痴呆大鼠学习记忆障碍的改善作用  

Effects of Huazhuo Jiedu Shugan Formula on ameliorating learning and memory impairment in a rat model of vascular dementia via SIRT1/PGC-1α/PPARγpathway

作　　者：王池 孙淑洁 刘佳 李淙 芦晔 裴林 WANG Chi;SUN Shu-jie;LIU Jia;LI Cong;LU Ye;PEI Lin(Hebei University of Chinese Medicine,Shijiazhuang 050200,China;Hebei Provincial Academy of Traditional Chinese Medicine,Shijiazhuang 050038,China;Hebei Provincial Key Laboratory of Turbid Pathogen&Toxin Syndromes,Shijiazhuang 050038,China)

机构地区：[1]河北中医药大学,河北石家庄050200 [2]河北省中医药科学院,河北石家庄050038 [3]河北省浊毒证重点实验室,河北石家庄050038

出　　处：《中成药》2025年第3期782-789,共8页Chinese Traditional Patent Medicine

基　　金：国家中医药管理局裴林全国名老中医专家传承工作室项目(国中医药人教函[2022]75号);河北省自然科学基金(H2023423049);河北省中医药管理局项目(2022113);河北省研究生创新基金项目(XCXZZBS2023011)。

摘　　要：目的探究化浊解毒疏肝方调控SIRT1/PGC-1α/PPARγ通路对血管性痴呆(VD)大鼠学习记忆障碍的改善作用。方法SD大鼠随机分为假手术组、模型组、多奈哌齐组(0.5 mg/kg)和化浊解毒疏肝方低、中、高剂量组(2.7、5.4、10.8 g/kg),每组10只,采用双侧颈动脉永久性结扎法(2-VO)建立VD大鼠模型,通过Longa5级评分法判断神经行为学,Morris水迷宫实验确认造模成功与否,再灌胃给予相应剂量药物3周。给药结束后,通过行为学实验检测大鼠空间记忆能力,ELISA法检测血清IL-18、IL-1β水平,HE染色和尼氏染色观察海马CA1区组织病理改变及神经元形态,免疫组化和Western blot法检测海马组织SIRT1、PGC-1α、PPARγ蛋白表达。结果与假手术组比较,模型组大鼠逃避潜伏期延长(P<0.01),穿越平台次数及目标象限停留时间减少(P<0.01),海马CA1区神经元排列松散,细胞核固缩,尼氏小体数量减少,海马组织IL-1β、IL-18分泌及蛋白表达均升高(P<0.01),海马组织SIRT1、PGC-1α、PPARγ蛋白表达降低(P<0.01);与模型组比较,多奈哌齐组和化浊解毒疏肝方各剂量组大鼠逃避潜伏期缩短(P<0.05,P<0.01),穿越平台次数及目标象限停留时间增加(P<0.05,P<0.01),海马CA1区损伤有所好转,海马组织IL-1β、IL-18分泌及蛋白表达均降低(P<0.05,P<0.01),海马组织SIRT1、PGC-1α、PPARγ蛋白表达升高(P<0.05,P<0.01)。结论化浊解毒疏肝方可能通过激活SIRT1/PGC-1α/PPARγ信号通路减轻炎症反应,改善VD大鼠学习记忆障碍。AIM To investigate the effects of Huazhuo Jiedu Shugan Formula(HJSGF)on improving learning and memory impairment in a rat model of vascular dementia(VD)via SIRT1/PGC-1α/PPARγpathway.METHODS The SD rats were randomly divided into the sham control group,the model group,the donepezil group(0.5 mg/kg),and the low-,medium-and high-dose HJSGF groups(2.7,5.4,10.8 g/kg),with 10 rats in each group.The VD rat models established by bilateral common carotid artery permanent ligation(2-VO)had their neurological behavior assessment using the Longa5-point scale,and their modeling success confirmed by the Morris water maze test and their 3-week corresponding dosing of drugs by gavage afterward.After the drug administration,the rats had their spatial memory ability tested through behavioral experiments;their serum levels of IL-18 and IL-1βmeasured by ELISA;their histopathological changes and neuronal morphology in the hippocampal CA1 region observed by HE staining and Nissl staining;and their hippocampal protein expressions of SIRT1,PGC-1αand PPARγdetected by immunohistochemistry and Western blot.RESULTS Compared with the sham control group,the model group showed prolonged escape latency(P<0.01);decreased platform crossing times and target quadrant residence time(P<0.01);disorganized arrangement of hippocampal CA1 neurons,nuclear condensation,reduced Nissl bodies,increased secretion and protein expressions of IL-1βand IL-18(P<0.01);and reduced hippocampal protein expressions of SIRT1,PGC-1αand PPARγ(P<0.01).Compared with the model group,the groups intervened with donepezil or HJSGF showed shortened escape latency(P<0.05,P<0.01);increased platform crossing times and target quadrant residence time(P<0.05,P<0.01);alleviated damage of the hippocampal CA1 region,reduced secretion and protein expressions of IL-1βand IL-18(P<0.05,P<0.01);and elevated hippocampal protein expressions of SIRT1,PGC-1αand PPARγ(P<0.05,P<0.01).CONCLUSION HJSGF may alleviate the inflammatory responses in VD rats and therefore improve their learning

关 键 词：化浊解毒疏肝方 血管性痴呆 学习记忆障碍 炎症反应 SIRT1/PGC-1α/PPARγ信号通路 

分 类 号：R285.5[医药卫生—中药学]