吉马酮对大鼠缺血性脑卒中的神经保护作用研究  

Neuroprotective effects of germacrone on rats with ischemic stroke

作　　者：屈战利 曾锦明 熊建 张杨威 杨旭[1] 季一飞 QU Zhanli;ZENG Jinming;XIONG Jian;ZHANG Yangwei;YANG Xu;JI Yifei(Department of Neurology,Nanchong Hospital of Beijing Anzhen Hospital(Nanchong Central Hospital)of Capital Medical University,Nanchong,Sichuan 637000,China;Department of Anesthesiology,Nanchong Hospital of Beijing Anzhen Hospital(Nanchong Central Hospital)of Capital Medical University,Nanchong,Sichuan 637000,China)

机构地区：[1]首都医科大学附属北京安贞医院南充医院(南充市中心医院)神经内科,四川南充637000 [2]首都医科大学附属北京安贞医院南充医院(南充市中心医院)麻醉科,四川南充637000

出　　处：《湖南中医药大学学报》2024年第6期943-950,共8页Journal of Hunan University of Chinese Medicine

基　　金：四川省自然科学基金项目(2022NSFSC0756)。

摘　　要：目的研究吉马酮对缺血性脑卒中大鼠和缺氧缺糖神经元细胞损伤的保护作用及可能机制。方法将SD大鼠随机分为假手术组(等体积生理盐水)、模型组(等体积生理盐水)、阳性药组(尼莫地平,10 mg/kg)及吉马酮低(5 mg/kg)、中(10 mg/kg)、高(20 mg/kg)剂量组,每组20只。采用线栓法制备缺血性脑卒中大鼠模型,用药组均于缺血1.5 h时腹腔注射给药1次。记录各组大鼠术后24 h的脑指数、脑组织含水量、神经功能评分、海马区组织形态学及脑组织胱天蛋白酶-3(cysteine aspartic acid specific protease-3,Caspase-3)活性和细胞凋亡水平,检测血清中氧化应激因子包括超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)和谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)水平,检测血清炎症因子包括肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、白细胞介素-1β(interleukin-1β,IL-1β)水平。原代大鼠神经元分为对照组、模型组、阳性药组(尼莫地平,1μmol/L)及吉马酮低(50μmol/L)、中(100μmol/L)、高(200μmol/L)剂量组。细胞预处理24 h后,除对照组外,各组细胞均进行氧糖剥夺和复糖复氧实验。实验结束后,检测各组细胞生存率、Caspase-3活性和细胞凋亡情况。结果与假手术组相比,模型组大鼠脑指数、脑组织含水量、神经功能评分均增加(P<0.05或P<0.01),血清中炎症因子TNF-α、IL-6和IL-1β的水平升高(P<0.01),氧化应激因子SOD和GSH-Px水平降低(P<0.01),MDA水平升高(P<0.01),Caspase-3活性增强(P<0.01),神经元细胞出现典型的坏死特征,细胞凋亡率增加(P<0.01)。与模型组相比,阳性药组和吉马酮不同剂量组大鼠脑指数、脑组织含水量、神经功能评分均下降(P<0.05或P<0.01),血清中炎症因子TNF-α、IL-6和IL-1β水平降低(P<0.05或P<0.01),氧化应激因子SOD和GSH-Px水平升高(P<0.05或P<0.01),MDA水平降低(P<0.05或P<0.01),CaspaObjective To study the protective effects and possible mechanism of germacrone on rats with ischemic stroke and on neuron damage caused by oxygen-glucose deprivation.Methods SD rats were randomized into sham-operated group(an equal volume of saline),model group(an equal volume of saline),positive drug group(nimodipine,10 mg/kg),and low-(5 mg/kg),medium-(10 mg/kg),and high-dose(20 mg/kg)germacrone groups,with 20 rats in each group.The ischemic stroke rat model was prepared by the thread embolism method,and each drug group was injected intraperitoneally with the corresponding drug once at 1.5 h post-ischemia.Postoperative measurements at 24 hours for each group of rats included brain index,brain tissue water content,neurological function score,hippocampal tissue morphology,and cysteine aspartic acid specific protease-3(Caspase-3)activity and apoptosis levels in the brain tissue.The serum levels of oxidative stress factors,including superoxide dismutase(SOD),malondialdehyde(MDA),and glutathione peroxidase(GSH-Px),as well as those of inflammatory factors,including tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)were all measured.Primary rat neurons were divided into control group,model group,positive drug group(nimodipine,1μmol/L),and low-(50μmol/L),medium-(100μmol/L),and high-dose(200μmol/L)germacrone groups.After 24 h of cell pre-treatment,the cells in all groups were subjected to oxygen-glucose deprivation and reglucose-reoxygenation except the control group.After the experiment,the survival rate,Caspase-3 activity,and apoptosis of cells were measured in each group.Results Compared with the sham-operated group,the model group exhibited increased brain index,brain tissue water content,and neurological function score(P<0.05 or P<0.01);the serum levels of inflammatory factors TNF-α,IL-6,and IL-1βwere elevated(P<0.01);the serum levels of oxidative stress factors SOD and GSH-Px were reduced(P<0.01),while that of MDA increased(P<0.01);Caspase-3 activity was higher(P<0.01),and the ne

关 键 词：吉马酮 缺血性脑卒中 神经元细胞 氧化应激 细胞凋亡 

分 类 号：R285.5[医药卫生—中药学]