摘要
目的:探究糖-钠协同转运蛋白2(Sodium-glucose cotransporter2,SGLT2)抑制剂对心力衰竭合并糖尿病小鼠治疗效果及左心室重构影响的实验研究。方法:选择4周龄雄性C57BL/6J小鼠,通过高脂饮食和免疫抑制剂他克莫司(Tacrolimus,TAC)诱导心力衰竭建立心衰合并糖尿病模型,分为三组:对照组(正常脂肪饮食)、模型组(高脂饮食第2周,TAC诱导心力衰竭)、SGLT2抑制剂组(高脂饮食+恩格列净灌胃第2周,同时TAC诱导心力衰竭)。治疗6周后,记录并比较各组小鼠死亡案例和生存率;酶联免疫吸附实验检测各组小鼠的白细胞介素-6(interleukin 6,IL-6)、IL-10、肿瘤坏死因子--α(tumor necrosis factor-α,TNF-α)的含量;50MHz传感器耦合的Vevo 2100系统进行超声心动图评估;逆转录聚合酶链式反应(reverse transeription-polymerase chain reaction,RT-PCR)实时分析p53、p21和p16的m RNA表达;蛋白印迹分析组织因子血管细胞黏著因子(Vascular cell Adhesion Molecule-1,VCAM-1)、SGLT1、SGLT2、一氧化氮合酶(endothelial nitric oxide synthase,eNOS)蛋白表达。结果:10天内模型组较对照组和SGLT2抑制剂组生存率降低(P<0.05),第20天、40天时模型组较对照组大鼠生存率降低,SGLT2抑制剂组较模型组的生存率升高(P<0.05)。模型组较对照组IL-6和TNF-α含量、右心室收缩压(right Ventricular Systolic Pre-ssure,RVSP)和平均肺动脉压(mean Pulmonary Artery Pressure,m PAP)水平、p53、p21和p16的m RNA表达量、VCAM-1、SGLT1、SGLT2的蛋白表达量以及左心室收缩末前后径(left ventricular end-systolic diameter,LVESD)、左心室舒张末前后径(left ventricular end-diastolic diameter,LVEDD)、左心室收缩末容量(left ventricular end-systolic volume,LVESV)均显著升高,IL-10含量、肺动脉血流加速时间(Pulmonary artery acceleration time,PAAT)水平、eNOS蛋白表达量以及左心室射血分数(left ventricular ejection fraction,LVEF)均显著降低(P<0.05),SGLT2抑制剂组较对照组以上指标变化均与上述相反,且差异具有统计学意义(P<0.05)。结论:选择性SGLT2抑制剂恩格列净改善了心衰合并糖尿病小鼠的收缩压,心脏重塑和内皮功能障碍。促进心脏的保护作用,同时改善左心室重量和体积及后壁厚度。
Objective:To investigate the effect of sugar-sodium cotransporter 2 inhibitor on the treatment effect and left ventricular remodeling in mice with heart failure and diabetes.Methods:Four-week-old male C57 BL/6 J mice were selected to induce heart failure through high-fat diet and TAC to establish a model of heart failure with diabetes and divided into three groups:control group(normal fat diet),model group(the second week of high-fat diet,TAC induces heart failure)and SGLT2 inhibitor group(high-fat diet+empagliflozin gavage for the second week,while TAC induced heart failure).After 6 weeks of treatment,the death cases and survival rates of mice were recorded and compared in each group;Enzyme-linked immunosorbent assay was used to detect the levels of IL-6,IL-10 and TNF-αin each group of mice;Vevo 2100 system coupled with 50 MHz sensor for echocardiographic evaluation;RT-PCR real-time analysis of the m RNA expression of p53,p21 and p16;Western blot analysis of tissue factor VCAM-1,SGLT1,SGLT2,eNOS protein expression.Results:The survival rate of the model group was lower than that of the control group and the SGLT2 inhibitor group within 10 days(P<0.05).The survival rate of the model group was lower than that of the control group on the 20 th and 40 th day,and the survival rate of the SGLT2 inhibitor group was higher than that of the model group.(P<0.05).Compared with the control group,IL-6 and TNF-αlevels,RVSP and m PAP levels,m RNA expression of p53,p21 and p16,protein expression of VCAM-1,SGLT1,SGLT2,and LVESD,LVEDD,and LVESV were significantly increased in the model group compared with the control group,while IL-10 content,PAAT level,eNOS protein expression and LVEF were significantly reduced(P<0.05).Compared with the control group,the changes of the above indicators in the SGLT2 inhibitor group were all opposite to the above,and the difference was statistically significant(P<0.05).Conclusion:The selective SGLT2 inhibitor Enpagliflozin improved the systolic blood pressure,heart remodeling and endothelial dysfunction in mice with heart failure and diabetes.Promote the protective effect of the heart,while improving the weight and volume of the left ventricle and the thickness of the posterior wall.
作者
杨莉
张旭东
詹小青
肖丽君
彭晓捷
李伟
YANG Li;ZHANG Xu-dong;ZHAN Xiao-qing;XIAO Li-jun;PENG Xiao-jie;LI Wei(Department of Gastroenterology and Endocrinology,Guangdong Provincial General Hospital of Armed Police Force,Guangzhou,Guangdong,510507,China)
出处
《现代生物医学进展》
CAS
2021年第16期3032-3037,共6页
Progress in Modern Biomedicine
基金
广东省医学科学技术研究基金项目(B2020048)。
关键词
糖-钠协同转运蛋白2
恩格列净
心衰
糖尿病
Sugar-sodium cotransporter 2 inhibitor
Empagliflozin
Heart failure
Diabetes
