恩格列净通过抑制iNOS改善脂多糖诱导的高血糖和对心脏功能的影响

Improvement of LPS-induced hyperglycemia by empagliflozin through inhibition of iNOS and its effect on cardiac function

目的 研究恩格列净(Empa)对脓毒血症大鼠心脏功能的影响,并探究其对脂多糖(LPS)诱导的高血糖、诱导型一氧化氮合酶(iNOS)表达和一氧化氮(NO)水平的作用。方法 20只SD大鼠按数字表法随机分为4组,分别接受单纯生理盐水(NS)、Empa、LPS、LPS联合Empa(LPS+Empa),每组均为5只。大鼠腹腔注射LPS(20 mg/kg)和/或Empa(5 mg/kg),均为单次注射。分别于注射后0、60、120、180和240 min检测尾静脉血糖水平。结束后,通过心室内插管检测左心室舒张末期压力(LVEDP)、心室压力变化最大上升速率(+dP/dt)和最大下降速率(-dP/dt),蛋白质免疫印迹检测iNOS蛋白表达,ELISA检测心脏组织中NO水平。结果 与NS组相比,LPS组在腹腔注射LPS后血糖升高(P<0.05),LVEDP和-dP/dt均升高(P<0.05),+dP/dt降低(P<0.05),而心脏组织中iNOS表达和NO水平均增加(P<0.05);与LPS组相比,LPS联合Empa能够改善LPS诱导的上述指标的变化(P<0.05)。结论 Empa可以改善LPS诱导的心脏功能异常,分析机制可能与其改善高血糖,降低心脏组织中iNOS表达和NO水平有关。

ObjectiveTo investigate the impact of empagliflozin(Empa)on cardiac function in septic rats,and to explore its effects on LPS-induced hyperglycemia and the expression of iNOS,as well as the level of NO.MethodsTwenty SD rats were randomly divided into four groups,i. e. the normal saline(NS)group,the Empa group,the LPS group and the LPS combined with Empa group(or the LPS+Empa group),each consisting of 5 animals. The rats received single injections of LPS(20 mg/kg)or/and Empa(5 mg/kg)intraperitoneally. Blood glucose levels were measured at 0,60,120,180 and 240 minutes after injection. After glucose detection,left ventricular end diastolic pressure(LVEDP),the maximum rate of increase(+dP/dt)and the maximum rate of decline(-dP/dt)in ventricular pressure were detected through intraventricular intubation. Western blot was used to detect the expression of iNOS and ELISA was used to detect NO level in the heart tissue.ResultsCompared with those of the NS group,the levels of serum glucose, LVEDP and-dP/dt of the LPS group increased after intraperitoneal injection of LPS(P<0. 05),the level of +dP/dt decreased(P<0. 05),while the expression levels of iNOS and NO increased in the heart tissue(both P<0. 05). Compared with those of the LPS group,LPS combined with Empa could improve the levels of the above-mentioned indicators induced by LPS(both P<0. 05).ConclusionEmpa could improve LPS-induced cardiac dysfunction,the mechanism of which might be related with the improvement of hyperglycemia and reduction of the expression levels of iNOS and NO in the cardiac tissue.