吴茱萸次碱对局灶性脑缺血模型大鼠脑组织病理、免疫失衡和氧化应激的调节作用及机制研究  

Regulatory effect and mechanism of rutaecarpine on brain histopathology,immune imbalance and oxidative stress in rats with focal cerebral ischemia

作　　者：周海燕[1] 周俐红[1] 张彩霞[1] 周立 韩玉华[1] ZHOU Hai-Yan;ZHOU Li-Hong;ZHANG Cai-Xia;ZHOU Li;HAN Yu-Hua(The Second Department of Neurology,Xinxiang Central Hospital,Xinxiang 453000,China)

机构地区：[1]新乡市中心医院神经内二科,新乡453000 [2]新乡医学院人体解剖学教研室,新乡453000

出　　处：《中国免疫学杂志》2020年第6期677-681,共5页Chinese Journal of Immunology

基　　金：河南省科技攻关计划基金资助项目(2015072521)。

摘　　要：目的:探究吴茱萸次碱(Rut)对局灶性脑缺血模型大鼠脑组织病理,免疫失衡和氧化应激的调节作用及机制研究。方法:大鼠随机分为空对照(Control)组,局灶性脑缺血模型(CI/R)组,Rut 5、10、20 mg/kg组,经过对应剂量的Rut灌胃处理后,除Control组外其余各组建立大鼠CI/R模型,进行神经功能评分,记录大鼠双侧贴纸去除时间,平衡木过杆时间,HE染色检测脑组织病理性改变,TUNEL染色检测脑组织细胞凋亡,RT-PCR检测Bax、Bcl-2基因表达,试剂盒检测白细胞介素6(IL-6)、IL-1β、IL-4、IL-10浓度及超氧化物歧化酶(SOD)、丙二醛(MDA)、乳酸脱氢酶(LDH)、活性氧(ROS)浓度,Western blot检测Caspase-3、核因子E2相关因子(Nrf2)、血红素氧化酶1(HO-1)、依赖还原型辅酶Ⅰ/Ⅱ醌氧化还原酶1(NQO1)蛋白表达。结果:与Control组比较,CI/R组大鼠神经功能评分、双侧贴纸去除时间、平衡木过杆时间增加,脑组织发生明显病理性改变并且细胞凋亡增加,IL-6、IL-1β浓度升高,IL-4、IL-10浓度降低,SOD浓度降低,MDA、LDH、ROS浓度升高,Nrf2/HO-1/NQO1通路受到抑制;与CI/R组比较,Rut 5、10、20 mg/kg组神经功能损伤、病理性改变得到明显缓解,细胞凋亡减少,IL-6、IL-1β、MDA、LDH、ROS浓度降低,IL-4、IL-10、SOD浓度升高,Nrf2/HO-1/NQO1通路激活。结论:Rut对局灶性脑缺血具有脑组织保护作用,并缓解免疫失衡和氧化应激,其机制可能是通过Nrf2/HO-1/NQO1通路激活实现。Objective:To investigate the regulation and mechanism of rutaecarpine(Rut)on brain histopathology,immune imbalance and oxidative stress in rats with focal cerebral ischemia.Methods:Rats were divided into Control,focal cerebral ischemia model(CI/R),Rut 5,10,20 mg/kg group,after treated with corresponding dose of Rut,CI/R model rats were established,neurological function score were determined,sticker removal and balance beam walking test were carried out,the pathological changes of brain tissue were observed by HE staining,and apoptosis of brain tissue were detected by TUNEL staining,RT-PCR was used to detect the gene expression of Bax and Bcl-2,the concentrations of IL-6,IL-1β,IL-4,IL-10 as well as superoxide dismutase(SOD),malondialdehyde(MDA),lactate dehydrogenase(LDH)and reactive oxygen species(ROS)were measured by kit,Western blot was used to detect the protein levels of Caspase-3,nuclear factor E2 related factor(Nrf2),heme oxidase1(HO-1)and NAD(P)H quinone oxidoreductase 1(NQO1).Results:Compared with Control group,in CI/R group the neurological function score as well as the time of sticker removal and balance beam walking test were increased,significant pathological change of brain was occurred and cell apoptosis was increased,the concentrations of IL-6,IL-1β,MDA,LDH,ROS were increased,and concentrations of IL-4,IL-10,SOD were decreased,the activation of Nrf2/HO-1/NQO1 pathway was inhibited.Compared with CI/R group,in Rut 5,10,20 mg/kg group the neurological damage and pathological change were significantly relieved,the cell apoptosis was decreased,the concentrations of IL-6,IL-1β,MDA,LDH,ROS were decreased,and concentrations of IL-4,IL-10,SOD were increased,the activation of Nrf2/HO-1/NQO1 pathway was activated.Conclusion:Rut has protective effects on brain tissue in focal cerebral ischemia,and alleviation role to immune imbalance and oxidative stress,which may be achieved through activation of Nrf2/HO-1/NQO1 pathway.

关 键 词：局灶性脑缺血 吴茱萸次碱 脑中风 Nrf2/HO-1/NQO1 

分 类 号：R743.3[医药卫生—神经病学与精神病学]