Nrf2激动剂CDDO-Im对高脂饮食诱导的肥胖小鼠肝脏脂肪变性的影响  

The Impact of the Nrf2 Activator CDDO-Im on Hepatic Steatosis in High-fat Diet-induced Obese Mice

作　　者：翟小莹 赵琳 夏煜栋 木尼拉·吐尔孙 焦谊 ZHAI Xiao-ying;ZHAO Lin;XIA Yu-dong;Munila·Tuersun;JIAO Yi(State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia,Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Xinjiang Medical University,Xinjiang Key Laboratory of Molecular Biology for Endemic Diseases,Urumqi,Xinjiang,830000,China;Division of Cardiology,Department of Internal Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,430030,China)

机构地区：[1]省部共建中亚高发病成因与防治国家重点实验室,新疆医科大学基础医学院生物化学与分子生物学教研室新疆地方病分子生物学重点实验室,新疆乌鲁木齐830000 [2]华中科技大学同济医学院附属同济医院心血管内科,湖北武汉430030

出　　处：《现代生物医学进展》2024年第5期822-827,886,共7页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(82260178);新疆维吾尔自治区"天山创新团队计划"项目(2022D14009)。

摘　　要：目的:探究Nrf2激动剂CDDO-Im对高脂饮食诱导的肥胖小鼠肝脏脂肪变性的作用。方法:33只雄性C57BL/6J小鼠随机分为两组:一组16只饲喂普通饲料,另一组17只饲喂高脂饲料建立肥胖模型。造模成功后将小鼠随机分成四组:普通饲料溶剂对照组(Control ND组)、普通饲料Nrf2激动剂组(Nrf2(+)ND组)、高脂饲料溶剂对照组(Control HFD组)和高脂饲料Nrf2激动剂组(Nrf2(+)HFD组)。分别给予Nrf2激动剂CDDO-Im和等体积溶剂灌胃干预6周后,检测各组小鼠血清甘油三酯(TG)、总胆固醇(T-CHO)和低密度脂蛋白-胆固醇(LDL-C)。苏木素-伊红(HE)染色观察肝脏组织形态学变化。RT-qPCR检测肝脏Nrf2下游抗氧化基因Nqo1、Ho1和Gclc的m RNA表达水平,Western Blot检测肝脏NQO1、HO-1和GCLC的蛋白表达水平。结果:与正常小鼠相比,肥胖小鼠的体重、TG和LDL-C升高(P<0.05),肝脏脂肪变性增加,GCLC的蛋白表达水平降低(P<0.05)。在肥胖小鼠中,与溶剂对照组相比,Nrf2激动剂组小鼠的体重、血清TG降低(P<0.05),肝脏脂肪变性减轻,Nqo1和Gclc的m RNA表达水平升高(P<0.05),NQO1和GCLC的蛋白表达水平升高(P<0.05)。结论:Nrf2激动剂CDDO-Im可改善高脂饮食诱导的肥胖小鼠肝脏脂肪变性,可能与Nrf2激动剂CDDO-Im激活抗氧化基因的表达来减轻肝细胞氧化应激有关。Objective:To investigate the effects of the Nrf2 activator CDDO-Im on hepatic steatosis in high-fat diet-induced obese mice.Methods:Thirty-three male C57BL/6J mice were randomly divided into two groups:one group of 16 mice was fed a normal diet,while the other group of 17 mice was fed a high-fat diet to establish an obesity model.After successful modeling,the mice were randomly divided into four groups:normal diet solvent control group(Control ND group),normal diet Nrf2 activator group(Nrf2(+)ND group),high-fat diet solvent control group(Control HFD group),and high-fat diet Nrf2 activator group(Nrf2(+)HFD group).Nrf2 activator CDDO-Im and an equal volume of solvent were administered by gavage for 6 weeks,and the serum triglycerides(TG),total cholesterol(T-CHO),and low-density lipoprotein cholesterol(LDL-C)levels were measured in all groups.Hematoxylin-eosin(HE)staining was performed to observe the morphological changes in liver tissues.RT-qPCR was used to detect the mRNA expression levels of liver Nrf2 downstream antioxidant genes Nqo1,Ho1,and Gclc,while Western Blot was used to assess the protein expression levels of NQO1,HO-1,and GCLC in the liver.Results:Compared with that in the normal mice,body weight,TG,LDL-C and hepatic steatosis in obese mice increased(P<0.05),while protein expression of GCLC decreased(P<0.05).In obese mice,compared with that in the solvent control group,body weight,serum TG levels and hepatic steatosis of mice in the Nrf2 activator group reduced(P<0.05),mRNA expression levels of Nqo1 and Gclc increased(P<0.05),and protein expression levels of NQO1 and GCLC elevated(P<0.05).Conclusion:The Nrf2 activator CDDO-Im can ameliorate hepatic steatosis in high-fat diet-induced obese mice,and its mechanism may be through upregulating the expression of antioxidant genes,thus inhibits hepatic oxidative stress.

关 键 词：肥胖 肝脂肪变性 核因子E2相关因子2 氧化应激 

分 类 号：R-33[医药卫生] R589.2R575.5