山姜素调节Shh/Gli1信号通路对缺血性脑卒中大鼠的神经保护作用研究  

Study on neuroprotective effect of alpinetin on ischemic stroke rats by regulating Shh/Gli 1 signaling pathway

作　　者：段姝洁 龚清源[1] 王彦丽[1] 戴启荷[1] DUAN Shujie;GONG Qingyuan;WANG Yanli;DAI Qihe(Department of Neurology,Jingzhou Central Hospital,Jingzhou 430000,China)

机构地区：[1]荆州市中心医院神经内科,荆州430000

出　　处：《中国免疫学杂志》2024年第11期2285-2289,2295,共6页Chinese Journal of Immunology

基　　金：2019年荆州市科技计划(2019HC03)。

摘　　要：目的:探究山姜素调节Shh/Gli1信号通路对缺血性脑卒中(IS)大鼠的神经保护作用。方法:随机选择15只大鼠作为对照组,其余大鼠构建IS模型,造模成功的大鼠随机分为模型组、山姜素组(5 mg/kg)、Shh/Gli1信号通路抑制剂环巴胺组(15 mg/kg)、山姜素+环巴胺组(5 mg/kg山姜素+15 mg/kg环巴胺),每组15只,给药1次/d,连续2周,对照组和模型组给予等量生理盐水。Zea-Longa评分法评估神经功能;ELISA检测炎症因子水平;称量脑组织质量,计算脑组织含水量;TTC染色测定脑梗死体积;HE染色观察神经细胞损伤;TUNEL染色检测神经细胞凋亡;qRT-PCR、Western blot检测Shh和Gli1 mRNA和蛋白表达。结果:对照组海马组织无任何异常现象,模型组大鼠海马组织结构异常,细胞排列紊乱,神经细胞出现核固缩现象,模型组较对照组细胞损伤率、Zea-Longa评分、梗死体积、IL-1β、IL-6、TNF-α、脑组织含水量、细胞凋亡率均显著升高(P<0.05),Shh、Gli1 mRNA和蛋白水平显著降低(P<0.05);与模型组相比,山姜素组细胞排列较为整齐,神经细胞核固缩现象改善,细胞损伤率、Zea-Longa评分、梗死体积、IL-1β、IL-6、TNF-α、脑组织含水量、细胞凋亡率均显著降低(P<0.05),Shh、Gli1 mRNA和蛋白水平显著升高(P<0.05),环巴胺组以上指标趋势相反,环巴胺逆转了山姜素对IS大鼠的神经保护作用。结论:山姜素可能通过激活Shh/Gli1信号通路对IS大鼠起神经保护作用。Objective:To investigate neuroprotective effect of alpinetin on ischemic stroke(IS)rats by regulating Shh/Gli1 signaling pathway.Methods:Fifteen rats were randomly collected as control group,remaining rats were used to construct an IS model.Rats that successfully modeling were randomly grouped into model group,alpinetin group(5 mg/kg),Shh/Gli1 signaling pathway inhibitor cycloparamide group(15 mg/kg)and alpinetin+cycloparamide group(5 mg/kg alpinetin+15 mg/kg cycloparamide),with 15 rats in each group,and administered once a day for two consecutive weeks,control group and model group were given equal amounts of physiological saline.Zea-Longa scoring method was applied to evaluate neural function;ELISA was applied to detect inflammatory factors levels;mass of brain tissue was weighed and water content of brain tissue was calculated;TTC staining was applied to measure volume of cerebral infarction;HE staining was applied to observe nerve cell damage;TUNEL staining was applied to detect neuronal apoptosis;qRT-PCR and Western blot were used to detect mRNA and protein expressions of Shh and Gli1.Results:There were no abnormalities in hippocampal tissue of control group,while hippocampal tissue structure of model group rats was abnor-mal,with disordered cell arrangement and nuclear pyknosis of nerve cells,cell damage rate,Zea-Longa score,infarct volume,IL-1β,IL-6,TNF-α,brain tissue water content,and cell apoptosis rate in model group were obviously higher than control group(P<0.05),mRNA and protein levels of Shh and Gli1 were obviously decreased(P<0.05);compared with model group,cells in alpinetin group were arranged more neatly,and phenomenon of neuronal cell nucleus pyknosis was improved,cell damage rate,Zea-Longa score,infarct volume,IL-1β,IL-6,TNF-α,brain tissue water content,and cell apoptosis rate were obviously decreased(P<0.05),mRNA and protein levels of Shh and Gli1 were obviously increased(P<0.05),trend of above indicators in cyclophosphamide group was opposite,ciclopramide reversed neuroprotective effect

关 键 词：山姜素 Shh/Gli1信号通路 缺血性脑卒中 神经保护 

分 类 号：R285.5[医药卫生—中药学]