白藜芦醇对糖尿病心肌病小鼠心肌细胞铁死亡的影响  

Effect of resveratrol on ferroptosis in cardiomyocytes of mice with diabetic cardiomyopathy

作　　者：王文秋 汪鹏[2] 卢清 和凤 王焱林[1] 柯剑娟[1] Wang Wenqiu;Wang Peng;Lu Qing;He Feng;Wang Yanlin;Ke Jianjuan(Department of Anesthesiology,Zhongnan Hospital of Wuhan University,Wuhan 430071,China)

机构地区：[1]武汉大学中南医院麻醉科,武汉430071 [2]武汉大学中南医院实验中心,武汉430071

出　　处：《中华麻醉学杂志》2023年第7期858-862,共5页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金(81471858)。

摘　　要：目的评价白藜芦醇对糖尿病心肌病小鼠心肌细胞铁死亡的影响。方法清洁级健康成年雄性C57BL/6小鼠30只,8周龄,体质量22~26 g。采用随机数字表法将其分为3组(n=10):对照组(C组)、糖尿病心肌病组(DCM组)和白藜芦醇组(RSV组)。采用连续5 d腹腔注射新鲜制备的链脲佐菌素40 mg·kg^(-1)·d^(-1)的方法制备小鼠糖尿病心肌病模型。模型制备成功后,RSV组小鼠连续12周经灌胃给予白藜芦醇25 mg·kg^(-1)·d^(-1),C组和DCM组小鼠给予等体积二甲基亚砜。于第12周末行超声心动图检查心脏结构及心功能情况,随后处死小鼠收集心肌组织标本,采用HE染色观察小鼠心肌组织病理学结果,透射电镜下观察小鼠心肌组织线粒体结构,采用比色法测定铁、MDA和谷胱甘肽(GSH)含量,Western blot法检测谷胱甘肽还原酶4(GPX4)表达。结果与C组比较,DCM组小鼠左室舒张末期内径(LVDd)和左室收缩末期内径(LVDs)升高,左室短轴缩短率(LVFS)和左室射血分数(LVEF)降低,心肌组织铁和MDA含量升高,GSH含量降低,GPX4表达下调(P<0.05);与DCM组比较,RSV组小鼠LVDd和LVDs降低,LVFS和LVEF升高,心肌组织铁和MDA含量降低,GSH含量升高,GPX4表达上调(P<0.05)。RSV组小鼠病理学损伤和线粒体结构损伤较DCM组明显减轻。结论白藜芦醇减轻糖尿病心肌病小鼠心肌损伤,进而改善心功能障碍的机制与抑制心肌细胞铁死亡有关。Objective To evaluate the effect of resveratrol on ferropotosis in cardiomyocytes of mice with diabetic cardiomyopathy.Methods Thirty healthy adult male C57BL/6 mice,aged 8 weeks,weighing 22-26 g,were divided into 3 groups(n=10 each)using a random number table method:control group(group C),diabetic cardiomyopathy group(group DCM)and resveratrol group(group RSV).Freshly prepared streptozotocin(STZ)40 mg·kg^(-1)·d^(-1)was intraperitoneally injected for 5 consecutive days to develop the model of type 1 diabetes mellitus.After the model was successfully developed,resveratrol 25 mg·kg^(-1)·d^(-1)was intragastrically given for 12 consecutive weeks in group RSV,while the equal volume of dimethyl sulfoxide was given instead in group C and group DCM.Echocardiography was performed to examine the cardiac structure and function at the end of the 12th week.Then mice were sacrificed,and myocardial tissue specimens were harvested for microscopic examination of the pathological changes of myocardial tissues(by Hematologist-Eosin staining)and mitochondrial morphology of myocardial cells(with a transmission electron microscope)and for determination of the contents of iron,malondialdehyde(MDA)and glutathione(GSH)(by colorimetry)and expression of glutathione peroxidase 4(GPX4)(by Western blot).Results Compared with group C,the left ventricular end-diastolic diameter and left ventricular end-systolic diameter were significantly increased,the left ventricular ejection fraction and left ventricular fractional shortening were decreased,the contents of iron and MDA were increased,the content of GSH was decreased,and the expression of GPX4 was down-regulated in group DCM(P<0.05).Compared with group DCM,the left ventricular end-diastolic diameter and left ventricular end-systolic diameter were significantly decreased,the left ventricular fractional shortening and ejection fraction were increased,the contents of iron and MDA were decreased,the content of GSH was increased,the expression of GPX4 was up-regulated(P<0.05),and the pathologi

关 键 词：白藜芦醇 糖尿病心肌病 铁死亡 

分 类 号：R587.2[医药卫生—内分泌] R542.2[医药卫生—内科学]