甲基巴多索隆通过激活Nrf2/HO-1减轻创伤性脑损伤大鼠氧化应激和炎症反应  

Methyl badosolone reduces oxidative stress and inflammatory response in rats with traumatic brain injury by activating Nrf2/HO-1

作　　者：李成建 徐兰娟 安婷婷 刘静 吴琼 靳婕 丁慧慧 马轶凡 李向阳 贾宝辉 Li Chengjian;Xu Lanjuan;An Tingting;Liu Jing;Wu Qiong;Jin Jie;Ding Huihui;Ma Yifan;Li Xiangyang;Jia Baohui(Department of Intensive Care Medicine,Zhengzhou Central Hospital Affiliated to Zhengzhou University,Zhengzhou 450001,China)

机构地区：[1]郑州大学附属郑州中心医院重症医学科,郑州450001

出　　处：《中华急诊医学杂志》2025年第2期200-207,共8页Chinese Journal of Emergency Medicine

基　　金：2021年度河南省高等学校重点科研项目计划(21A320056);2023年度河南省医学科技攻关计划联合共建项目(LHGJ20230779);2021年度河南省科技攻关项目(212102310673)。

摘　　要：目的探讨甲基巴多索隆(methyl badosolone,CDDO-Me)对创伤性脑损伤(traumatic brain injury,TBI)大鼠的保护作用及作用机制。方法8周龄SPF级SD大鼠随机(随机数字法)分为4组(n=18):假手术组(Sham)、TBI组、溶媒对照组(TBI+Vehicle)和TBI+CDDO-Me组。采用液压冲击颅脑损伤法建立大鼠TBI模型。TBI+CDDO-Me组在造模后30 min经腹腔注射CDDO-Me(溶于1%DMSO中,剂量为10 mg/kg),2次/d,共给药3 d。造模后第3天行mNSS评分后取脑组织行病理学及含水量检测,采用免疫荧光双标染色检测核因子E2相关因子2(nuclear factor erythroid2 related factor 2,Nrf2)的表达;采用免疫组织化学染色检测离子钙接头分子-1(ionized calcium binding adapter molecule-1,Iba-1)的表达;采用ELISA法检测血清中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白介素(interleukin,IL)-1β和IL-18的含量;采用试剂盒检测丙二醛(malondialdehyde,MDA)和活性氧(reactive oxygen species,ROS)的含量;Western blot检测Nrf2通路、B细胞淋巴瘤-2(B-cell lymphoma-2,BCL-2)和BCL-2相关蛋白(BCL-2 associated X protein,BAX)的表达。结果(1)与Sham组相比较,TBI组大鼠mNSS评分和损伤侧大脑皮层含水量均明显升高(均P<0.05),CDDO-Me干预后均明显下降(均P<0.05)。(2)与Sham组相比,TBI组大鼠尼氏染色损伤神经元和凋亡阳性细胞比例均明显升高(均P<0.05),CDDO-Me干预后均明显下降(均P<0.05),且伴随着BAX蛋白表达下降,BCL-2蛋白表达上调(均P<0.05)。(3)免疫荧光和Western blot结果显示,与Sham组相比较,TBI组总Nrf2、胞核Nrf2、HO-1、NQO1蛋白表达均有所升高(均P<0.05),CDDO-Me干预后升高更加明显(均P<0.05)。(4)免疫组织化学及ELISA结果显示,与Sham组相比较,TBI组大鼠脑组织中MDA、ROS、Iba-1含量和血清中TNF-α、IL-1β和IL-18含量均明显升高(均P<0.05),CDDO-Me干预后均明显下降(均P<0.05)。结论CDDO-Me有助于减轻TBI大鼠氧化应激及炎症反应,其机制可能与激活Nrf2/HO-1抗氧化�Objective Explore the protective effect and mechanism of methyl badosolone(CDDO-Me)on rats with traumatic brain injury(TBI).Methods A total of 72 SPF-grade SD rats aged 8 weeks were randomly(random number)divided into 4 groups(n=18)using the random number table method:Sham,TBI,TBI+Vehicle,and TBI+CDDO-Me.The rat TBI model was established using the hydraulic impact head injury method.The TBI+CDDO-Me group was administered CDDO-Me(dissolved in 1%DMSO,at a dose of 10 mg/kg)via intraperitoneal injection 30 minutes after modeling,twice a day for a total of 3 days.On the third day after modeling,brain tissue was collected for pathological and water content detection after mNSS scoring.Immunofluorescence double staining was used to detect the expression of nuclear factor erythroid2 related factor 2(Nrf2);immunohistochemical staining was used to detect the expression of ionized calcium binding adapter molecule-1(Iba-1);ELISA was used to detect the levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,and IL-18 in serum;kits were used to detect the levels of malondialdehyde(MDA)and reactive oxygen species(ROS);Western blot was used to detect the expression of the Nrf2 pathway,B-cell lymphoma-2(BCL-2),and BCL-2 associated X protein(BAX).Results(1)Compared with the Sham group,the mNSS scores and water content in the injured cortex of the TBI group rats were signifi cantly increased(both P<0.05),and both signifi cantly decreased after CDDO-Me intervention(both P<0.05).(2)Compared with the Sham group,the proportion of Nissl-stained injured neurons and apoptotic positive cells in the TBI group rats were significantly increased(both P<0.05),and both significantly decreased after CDDO-Me intervention(both P<0.05),accompanied by a decrease in BAX protein expression and upregulation of BCL-2 protein expression(both P<0.05).(3)Immunofluorescence and Western blot results showed that compared with the Sham group,the expression of total Nrf2,nuclear Nrf2,HO-1,and NQO1 proteins in the TBI group were all increased(all P<0.05),a

关 键 词：创伤性脑损伤 甲基巴多索隆 氧化应激 炎症 核因子E2相关因子2 

分 类 号：R73[医药卫生—肿瘤]