基于Nrf2/HO-1信号通路探讨脑清通颗粒对脑缺血再灌注大鼠的保护作用及机制  

Protective Effects and Mechanism of Naoqingtong(脑清通)Granule on Cerebral Ischemia Reperfusion in Rats Based on Nrf2/HO-1 Signaling Pathway

作　　者：严亚锋[1,2] 刘伟 王斌[1] 刘继平[1] 王川[1] YAN Yafeng;LIU Wei;WANG Bin;LIU Jiping;WANG Chuan(Shaanxi University of Chinese Medicine,Xianyang712046;Shaanxi Provincial Key TCM Laboratory of Encephalopathy,Xianyang 712046)

机构地区：[1]陕西中医药大学,咸阳712046 [2]陕西省中医脑病学重点实验室,咸阳712046

出　　处：《中药药理与临床》2024年第3期23-28,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：陕西省中医药管理局课题(编号:2021-ZZ-JC043);陕西省科技厅课题(编号:2023-JC-QN-0821);陕西省教育厅课题(编号:22JK0348);陕西中医药大学学科创新团队(编号:2019-YL13)。

摘　　要：目的:探讨脑清通颗粒对大鼠脑缺血再灌注损伤的保护作用及机制。方法:90只大鼠随机分为假手术对照组、模型对照组、尼莫地平6.25 mg/kg组、脑清通颗粒1.3、2.6、5.2 g/kg组,每组15只。除假手术对照组外,其余各组采用高脂饲料喂养、复合应激刺激和线栓法制备脑缺血再灌注大鼠模型。从第6 w起,假手术对照组和模型对照组用等体积生理盐水灌胃,其余各给药组用相应药物灌胃,1次/d,连续给药7 d。观察大鼠体征表现;采用神经功能评分、TTC染色及脑梗死体积测定评价脑缺血再灌注模型;尼氏染色观察神经细胞变化;ELISA法检测SOD活力和MDA含量;免疫组化法和Western blot法检测Keap1、Nrf2和HO-1的蛋白表达。结果:与正常对照组比较,模型对照组大鼠体征表现符合临床肝热痰瘀证基本特征,神经功能评分、脑梗死体积显著增加,大鼠血清SOD活力显著降低,MDA含量明显升高,脑组织Keap1、Nrf2、HO-1的蛋白表达明显上调(P<0.05或P<0.01);与模型对照组比较,脑清通颗粒1.3、2.6、5.2 g/kg组可改善大鼠体征表现,明显降低神经功能评分和脑梗死体积(P<0.01或P<0.05),显著升高血清SOD活力,降低MDA含量,下调脑组织Keap1的蛋白表达,上调Nrf2和HO-1的蛋白表达(P<0.01)。结论:脑清通颗粒可能是通过激活Nrf2/HO-1信号通路达到对脑缺血再灌注损伤的脑保护作用。Objective:To explore the protective effects and mechanism of Naoqingtong(脑清通)Granule on cerebral ischemia-reperfusion injury in rats.Method:Ninety rats were randomly divided into the sham operation control group,model control group,nimodipine 6.25 mg/kg group,Naoqingtong Granule 1.3 g,2.6 g and 5.2 g/kg groups,with 15 rats in each group.Except for the sham operation control group,the other groups were fed with high-fat diet and subjected to stress stimulation and thread occlusion to prepare the rat model of cerebral ischemia reperfusion.Starting from the 6th week,the sham operation control group and model control group were administered with equal volume of saline,while the other groups were given gavage of corresponding drugs once a day for 7 consecutive days.The signs and manifestations of rats were observed.The cerebral ischemia reperfusion model was evaluated with neurological function score,TTC staining,and cerebral infarction volume measurement.Nissl staining was performed to observe changes in nerve cells.ELISA method was used to detect the contents of SOD and MDA.The protein expressions of Keapl,Nrf2,and HO-1 were detected by immunohistochemistry and Western blot.Result:The physical signs of the model control group were consistent with the basic characteristics of clinical symptoms of Ganretanyu(肝热痰瘀)syndrome,exhibiting a significant increase in neurological function score and cerebral infarction volume(P<0.01),a significant decrease in serum SOD content(P<0.01),a significant increase in MDA content(P<0.01),a significant increase in protein expressions of Keapl and Nrf2 in brain tissue(P<0.01),and a significant increase in protein expression of H0-1(P<0.05 or P<0.01).Treatment with Naoqingtong Granule(1.3 g/kg,2.6 g/kg and 5.2 g/kg)could improve the physical signs and manifestations of rats,reduce neurological function scores and cerebral infarction volume(P<0.01 or P<0.05),increase serum SOD content(P<0.01),decrease MDA content(P<0.01),reduce the protein expression of Keapl in brain tissue(

关 键 词：脑清通颗粒 肝热痰瘀证 脑缺血再灌注损伤 血红素氧化酶(HO-1) 核因子E2相关因子2(Nrf2) 

分 类 号：R285.5[医药卫生—中药学]