基于Nrf2/HO-1及NF-κB信号通路探讨葛根素对大鼠脑出血后早期炎症反应及氧化应激反应的影响  

Effects of puerarin on early inflammatory and oxidative stress responses involving the Nrf2/HO-1 and NF-κB signaling pathways after intracerebral hemorrhage in rat models

作　　者：邹勇 顾应江 丁昊[1] 杨呈浩[1] 陈岷辉[1] 蔡昱 Zou Yong;Gu Yingjiang;Ding Hao;Yang Chenghao;Chen Minhui;Cai Yu(Department of Neurosurgery,Zigong Fourth People's Hospital,Zigong 643000,China;Department of Neurosurgery,the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University,Luzhou 646000,China)

机构地区：[1]自贡市第四人民医院神经外科,四川自贡643000 [2]西南医科大学附属中医医院神经外科,四川泸州646000

出　　处：《中华脑科疾病与康复杂志（电子版）》2023年第5期271-277,共7页Chinese Journal of Brain Diseases and Rehabilitation（Electronic Edition）

基　　金：自贡市2021年重点科技计划项目基金(2021YLSF13);2022年四川省卫生康复学院院级课题(CWKY-2022Y-07)。

摘　　要：目的探讨葛根素对大鼠脑出血(ICH)后神经功能的保护作用并初步分析其作用机制。方法采用随机数字表法将80只SD雄性大鼠分为假手术组、ICH组、低剂量组、高剂量组,每组20只。ICH组、低剂量组和高剂量组予以左侧尾状核区立体定向注射胶原酶Ⅰ型建立ICH模型,假手术组注射等体积的生理盐水溶液。低剂量组、高剂量组按照体质量给予葛根素腹腔注射治疗(低:50 mg/kg;高:100 mg/kg),假手术组、ICH组腹腔注射等量的溶解剂。分别于造模后1、3、5、7 d检测4组大鼠的神经功能缺损评分,造模后3 h及5 d时行MRI检测,大鼠处死后收集脑组织标本进行HE染色、免疫组化、Western blot等实验室指标检测。结果高剂量组和低剂量组大鼠在造模后3、5、7 d的神经功能缺损评分较ICH组明显降低,且高剂量组大鼠在造模后5和7 d的神经缺损评分较低剂量组降低,差异均具有统计学意义(P<0.05)。低剂量组和高剂量组大鼠造模后5 d的血肿体积和脑组织结构优于ICH组。与ICH组相比,低剂量组和高剂量组大鼠造模后7 d的NF-κB表达水平降低,Nrf2及HO-1表达水平升高,差异具有统计学意义(P<0.05)。此外,与ICH组比较,高剂量组和低剂量组大鼠造模后3、5、7 d的IL-10表达增加,IL-1β和TNF-α表达降低,差异具有统计学意义(P<0.05)。结论葛根素能减轻大鼠ICH后神经功能损伤,起到神经功能保护的作用,其作用机制可能与葛根素抑制NF-κB炎症通路因子、激活Nrf2/HO-1抗氧化通路有关。Objective To investigate the effects of puerarin on neural function after intracerebral hemorrhage(ICH)in rats and preliminarily analyze the underlying mechanisms.Methods Eighty male Sprague-Dawley male rats were randomly divided into 4 groups:the sham operation group,ICH group,low-dose group,and high-dose group,with 20 rats in each group.The rats in the ICH,low-dose,and high-dose groups received stereotactic injection of collagenase typeⅠinto the left caudate nucleus to establish the ICH model,while rats in the sham operation group were injected with the same amount of normal saline.Rats in the low-dose and high-dose groups were treated with intraperitoneal injection of puerarin according to their body mass(low:50 mg/kg;high:100 mg/kg),while rats in the sham operation group and ICH group were injected with the same amount of vehicle.The neurological deficit scores of 4 groups of rats were assessed on the 1st,3rd,5th,and 7th day after model establishment.MRI tests were performed on the 3rd and 5th day after model establishment.After the rats were sacrificed,brain tissue specimens were collected for laboratory indicators such as H&E staining,immunohistochemistry,Western blot.Results The neurological deficit scores of rats in the high-dose and low-dose groups were significantly lower than those in the ICH group at 3,5,and 7 d after modeling,and the neurological deficit scores of rats in the high-dose group were lower than those in the low-dose group at 5 and 7 d after modeling,all with statistically significant differences(P<0.05).The hematoma volume and brain histology of rats in the low-dose and high-dose groups were improved compared with those in the ICH group at 5 d after modeling.Compared with the ICH group,the NF-κB expression levels of rats in the low-dose and high-dose groups were reduced,and the expression levels of Nrf2 and HO-1 were increased at 7 d after modeling,with statistically significant differences(P<0.05).In addition,compared with the ICH group,the IL-10 expression levels of rats in the high

关 键 词：脑出血 葛根素 氧化应激反应 炎症反应 

分 类 号：R742.1[医药卫生—神经病学与精神病学]