司美格鲁肽对链脲佐菌素诱导的糖尿病心肌病大鼠的保护作用及其机制研究  

Protective effect of semaglutide on streptozotocin-induced diabetic cardiomyopathy in rats and its mechanism

作　　者：华炳红 张菊云 郑地明[1] 黄辛欣 Hua Binghong;Zhang Juyun;Zheng Diming;Huang Xinxin(Department of Endocrinology and Metabolism, Haikou Affiliated Hospital of Central South University,Hainan Province,Haikou 570203,China)

机构地区：[1]中南大学湘雅医学院附属海口医院内分泌代谢科,570203

出　　处：《疑难病杂志》2022年第7期742-747,共6页Chinese Journal of Difficult and Complicated Cases

基　　金：海南省卫生计生行业科研项目(1801320719A2003)。

摘　　要：目的观察司美格鲁肽对链脲佐菌素(STZ)诱导的糖尿病心肌病(DCM)大鼠心肌损伤的保护作用及其机制。方法2021年1月—2022年1月于中南大学湘雅医学院附属海口医院进行实验。60只雄性SD大鼠随机数字表法分为对照组、DCM组和干预组,各20只。DCM组和干预组采用一次性腹腔注射STZ(70 mg/kg)建立DCM模型,对照组以等量枸橼酸缓冲液替代。造模成功后干预组每日腹腔注射司美格鲁肽(10 nmol/kg)干预6周,对照组和DCM组以等量生理盐水替代。干预6周后,检测各组大鼠血清空腹血糖(FPG)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平。HE染色和Masson染色观察大鼠心肌组织形态变化并计算心肌组织胶原蛋白体积分数(CVF);免疫组化法检测心肌组织α-平滑肌肌球蛋白(α-SMA)和肿瘤坏死因子-α(TNF-α)的表达;Western-blot法检测各组大鼠心肌组织TNF-α和血管内皮生长因子(VEGF)蛋白表达。结果HE染色显示对照组大鼠心肌纤维形态均匀,排列规律紧密;DCM组大鼠心肌纤维断裂,排列紊乱;干预组大鼠心肌结构紊乱程度降低,心肌排列较DCM组规则。Masson染色显示,DCM组CVF高于对照组(t/P=4.118/0.026),干预组CVF低于DCM组(t/P=3.197/0.035)。DCM组大鼠血清FPG、TC、TG、LDL-C水平高于对照组,HDL-C低于对照组(t/P=41.913/<0.001、29.340/<0.001、10.321/<0.001、44.132/<0.001、23.235/<0.001);干预组大鼠血清FPG、TC、TG、LDL-C水平低于DCM组(t/P=20.179/<0.001、7.346/<0.001、3.629/0.001、43.365/<0.001);DCM组大鼠心肌组织TNF-α及其蛋白表达高于对照组,α-SMA、VEGF蛋白表达低于对照组(t/P=14.272/<0.001、4.006/0.016、7.278/<0.001、3.513/0.023);干预组大鼠心肌组织TNF-α及其蛋白表达低于DCM组,α-SMA、VEGF蛋白表达高于DCM组(t/P=13.062/<0.001、3.069/0.038、13.003/<0.001、2.134/0.046)。结论司美格鲁肽可能对STZ诱导的DCM具有保护作用,可在�Objective To observe the protective effect and mechanism of semaglutide on myocardial injury in rats with streptozotocin(STZ)-induced diabetic cardiomyopathy(DCM).Methods From January 2021 to January 2022,the experiment was conducted in Haikou Hospital Affiliated to Xiangya School of Medicine,Central South University.60 male SD rats were randomly divided into control group,DCM group and intervention group,20 rats in each group.In the DCM group and the intervention group,a one-time intraperitoneal injection of STZ(70 mg/kg)was used to establish the DCM model,and the control group was replaced with the same amount of citrate buffer.After successful modeling,the intervention group was given daily intraperitoneal injection of semaglutide(10 nmol/kg)for 6 weeks,and the control group and DCM group were replaced with the same amount of normal saline.After 6 weeks of intervention,serum fasting blood glucose(FPG),total cholesterol(TC),triacylglycerol(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were detected in each group.HE staining and Masson staining were used to observe the morphological changes of rat myocardial tissue and calculate myocardial collagen volume fraction(CVF).Immunohistochemistry was used to detect myocardial tissueα-smooth muscle myosin(α-SMA)and tumor necrosis factor-α(TNF-α)expression;Western-blot method was used to detect the expression of TNF-αand vascular endothelial growth factor(VEGF)protein in myocardial tissue of rats in each group.Results HE staining showed that the myocardial fibers in the control group were uniform in shape and closely arranged;the myocardial fibers in the DCM group were broken and disordered;Masson staining showed that the CVF of the DCM group was higher than that of the control group(t/P=4.118/0.026),and the CVF of the intervention group was lower than that of the DCM group(t/P=3.197/0.035).The levels of serum FPG,TC,TG and LDL-C in the DCM group were higher than those in the control group,while HDL-C was significantly

关 键 词：糖尿病心肌病 司美格鲁肽 微循环 心脏保护 大鼠 

分 类 号：R587.2[医药卫生—内分泌]