钠-葡萄糖协同转运蛋白2抑制剂达格列净对糖尿病心肌病小鼠心肌重构的影响  

Effects of sodium-glucose cotransporter 2 inhibitor dapagliflozin on myocardial remodeling in mice with diabetic cardiomyopathy

作　　者：李晓星[1] 张家俊 范欣慧 宋心天 徐峰[2,3,4] 季晓平[4] 陈玉国[2,3,4] 李传保[2,3,4] Li Xiaoxing;Zhang Jiajun;Fan Xinhui;Song Xintian;Xu Feng;Ji Xiaoping;Chen Yuguo;Li Chuanbao(Department of Geriatrics,Qilu Hospital of Shandong University,Jinan 250012,China;Department of Emergency Medicine and Chest Pain Center,Qilu Hospital of Shandong University,Jinan 250012,China;The Key Laboratory of Emergency and Critical Care Medicine of Shandong Province,Qilu Hospital of Shandong University,Jinan 250012,China;The Key Laboratory of Cardiovascular Remodeling and Function Research,Chinese Ministry of Education and Chinese Ministry of Public Health,Qilu Hospital of Shandong University,Jinan 250012,China)

机构地区：[1]山东大学齐鲁医院老年医学科,济南250012 [2]山东大学齐鲁医院急诊科、胸痛中心,济南250012 [3]山东大学齐鲁医院山东省急危重症重点实验室,济南250012 [4]山东大学齐鲁医院教育部与卫生部心血管重构与功能研究重点实验室,济南250012

出　　处：《中华老年医学杂志》2023年第9期1099-1104,共6页Chinese Journal of Geriatrics

基　　金：国家自然科学基金(82070388);国家自然科学基金(82170442);山东省泰山学者青年专家计划(tsqn202211310);山东省自然科学基金(ZR2020MH035)。

摘　　要：目的 探讨钠-葡萄糖协同转运蛋白2抑制剂达格列净对糖尿病心肌病小鼠心肌重构的影响及机制.方法 2021年1-12月选取60只6周龄雄性C57BL/6J小鼠,建立糖尿病心肌病鼠40只,成模28只,未干预组、达格列净治疗组(干预组)1∶1配比各14只,另外20只小鼠为对照组.干预组小鼠应用达格列净灌胃12周,超声检测各组小鼠心脏结构与功能,组织学与电镜评估心肌纤维化程度,酶联免疫吸附法检测炎症因子浓度,原位末端标记(TUNEL)染色观察心肌细胞凋亡,二氢乙锭荧光染色评价心肌氧化应激水平.结果 实验末干预组小鼠体重与空腹血糖略低于未干预组,但差异无统计学意义(P>0.05),而左心室射血分数优于未干预组[(61.07±4.66)%比(45.8±4.80)%(t=-5.24,P<0.05)];组织学结果显示干预组小鼠心肌肥厚、心肌细胞排列紊乱较未干预组减轻,胶原容积分数亦降低[(18.4±1.9)%比(31.8±3.7)%,t=-12.0,P<0.05].进一步研究结果显示,干预组小鼠炎症因子浓度降低,白介素-6(82.19±10.90)ng/L比(291.02± 31.02)ng/L(t=23.8);肿瘤坏死因子-α(70.45±12.13)ng/L 比(201.31±27.10)ng/L(t=16.5),穿透素 3(13.05±2.04)μg/L(42.40±1.26)μg/L(t=45.8),均 P<0.05;心肌凋亡指数 1.736±0.247比0.864±0.129(t=11.7,P<0.05),心肌氧化应激水平干预组1.274±0.298较未干预组2.655± 0.252改善(t=-13.3,P<0.05).结论 达格列净通过减轻心肌氧化应激和炎性反应改善心肌肥厚并抑制心肌纤维化,起到干预糖尿病小鼠心肌重构的作用,最终保护糖尿病心肌病小鼠的心功能.Objective To investigate the effects of sodium-glucose cotransporter 2 inhibitor dapagliflozin on myocardial remodeling in mice with diabetic cardiomyopathy and related mechanisms.Methods Between January and December 2021,606-week-old male C57BL/6J mice were chosen for the study,40 were used to establish a diabetic cardiomyopathy model and the model was established in 28 mice,of whom,14 were assigned to a non-intervention group and 14 to a dapagliflozin treatment group(intervention group).The rest of the 20 mice were in the control group.The mice in the intervention group were treated with dapagliflozin via oral gavage for 12 weeks.Cardiac structure and function were measured by ultrasound,the degree of myocardial fibrosis was evaluated by histology and electron microscopy,the concentrations of inflammatory factors were detected by enzyme-linked immunosorbent assays,apoptosis of myocardial cells was examined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling(TUNEL),and the level of myocardial oxidative stress was evaluated by dihydroethidium fluorescence.Results At the end of the experiments,the body weight and fasting blood glucose in the intervention group were slightly lower than in the non-intervention group,but the difference was not statistically significant,while values from cardiac function parameters such as left ventricular ejection fraction were more favorable than in the non-intervention group[(61.07±4.66)%vs.(45.8±4.80)%,t=-5.24,P<0.05].Compared with the non-intervention group,the intervention group had alleviated myocardial hypertrophy,less myocardial disarray,and reduced collagen volume fraction[(18.4±1.9)%vs.(31.8±3.7)%,t=-12.0,P<0.05].Furthermore,the concentrations of inflammatory factors in the intervention group were lower than in the control group[interleukin-6:(82.19±10.90)ng/L vs.(291.02±31.02)ng/L,t=23.8,P<0.05;tumor necrosis factor-α:(70.45±12.13)ng/L vs.(201.31±27.10)ng/L(t=16.5),P<0.05;perforin 3:(13.05±2.04)μg/L vs.(42.40±1.26)μg/L(t=45.8),P<0.05;the i

关 键 词：钠-葡萄糖协同转运蛋白2抑制剂 糖尿病 心肌疾病 心室重构 

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