达格列净对心力衰竭大鼠心功能和线粒体能量代谢的影响  

Effects of dapagliflozin on cardiac function and mitochondrial energy metabolism in heart failure rats

作　　者：崔文建[1] 吴荣[1] 刘野[1] 于妍[2] 李栋[2] CUI Wen-jian;WU Rona;LIU Ye;YU Yan;LI Dong(The Second Department of Cardiovascular Diseases,Gansu Provincial Hospital of Traditional Chinese Medicine,Lanzhou 730050,Gansu Province,China;The First Department Cardiovascular Diseases,Gansu Provincial Hospital of Traditional Chinese Medicine,Lanzhou 730050,Gansu Province,China)

机构地区：[1]甘肃省中医院心血管病二科,甘肃兰州730050 [2]甘肃省中医院心血管病一科,甘肃兰州730050

出　　处：《中国临床药理学杂志》2023年第9期1247-1251,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的探究钠-葡萄糖共转运蛋白2(SGLT2)抑制药达格列净对心力衰竭大鼠心功能和线粒体能量代谢的影响及其作用机制。方法将雄性健康SD大鼠按照随机数字表发分为对照组、模型组和低、中、高剂量实验组,每组10只。对照组大鼠正常饲养,其余组大鼠均构建心力衰竭模型,低、中、高剂量实验组大鼠在模型构建成功后分别每日灌胃给予0.10、0.25、0.50 mg·kg^(-1)的达格列净,连续给药4周。使用多普勒诊断仪检测心功能指标,主动脉采血后处死大鼠,取心脏组织;酶联免疫吸附测定法检测血清腺苷三磷酸(ATP)、腺苷二磷酸(ADP)以及腺苷一磷酸(AMP)水平,用考马斯亮蓝染色法检测Na^(+)-K^(+)ATP和Ca^(2+)-Mg^(2+)ATP酶活性,用TUNEL检测心肌组织细胞凋亡情况,用蛋白质印迹法检测心肌组织腺苷酸活化蛋白激酶(AMPK)、过氧化物酶体增殖物激活受体-γ共激活因子^(-1)α(PGC^(-1)α)蛋白表达水平。结果对照组、模型组和高剂量实验组大鼠左室舒张末内径值分别为(0.61±0.06)、(0.95±0.07)和(0.68±0.05)cm,左室轴缩短分数分别为(47.07±3.78)%、(20.61±1.54)%和(41.03±3.28)%,血清ATP含量分别为(771.57±75.94)、(424.87±36.48)和(709.06±6.90)μg·mL^(-1),心肌组织Na+-K+ATP酶活性分别为7.40±0.44、3.91±0.46和6.82±0.70,心肌组织Ca^(2+)-Mg^(2+)ATP酶活性分别为7.94±0.52、4.24±0.59和7.19±0.58,心肌细胞凋亡率分别为(3.44±0.32)%、(21.79±2.15)%和(8.92±0.70)%,心肌组织p-AMPK蛋白表达水平分别为0.35±0.02、0.93±0.09和0.41±0.04,心肌组织p-PGC^(-1)α蛋白表达水平分别为0.23±0.04、1.00±0.09和0.32±0.02。对照组的上述指标与模型组比较,高剂量实验组的上述指标与模型组比较,差异均有统计学意义(均P<0.05)。结论达格列净可通过调控线粒体能量代谢改善心力衰竭大鼠心功能,这可能是通过AMPK/PGC^(-1)α信号通路实现的。Objective To investigate the effects of dapagliflozin,an inhibitor of sodium glucose cotransporter 2,on cardiac function and mitochondrial energymetabolism in rats with heart failure and its mechanism.Methods According to the random number table,male healthy SD ratswere divided into control group,model group,experimental-L,experimental-M and experimental-H groups,with 10 rats in each group.The rats in the control group were fed normally,and the rats in the other groups were constructed heart failure models.The rats in the experimental-L,-M,-H groups were given 0.10,0.25,0.50 mg·kg^(-1)dapagliflozin daily for 4 weeks after the model was successfully constructed.The cardiac function indexes were detected by Doppler diagnostic instrument.After aortic blood sampling,the rats were killed and the heart tissue was harvested.Serum levels of adenosine triphosphate(ATP),adenosine diphosphate(ADP)and adenosine monophosphate(AMP)were measured by enzyme-linked immunosorbent assay.The activies of Na^(+)-K^(+) ATP Ca^(2+)-Mg^(2+) ATPase were detected by Coomassie brilliant blue staining,and the apoptosis of myocardial tissue was detected by TUNEL.Adenylate activated protein kinase(AMPK)and proliferator-activated receptor-coactivator-lα(PGC-lα)protein expression level were detected by Western blot of myocardial tissue.Results Left ventricular end diastolic dimension values of control,model and experimental-H groups were(0.61±0.06),(0.95±0.07),(0.68±0.05)cm;fractional shortening values were(47.07±3.78)%,(20.61±1.54)%,(41.03±3.28)%;ATP contents were(771.57±75.94),(424.87±36.48),(709.06±6.90)μg·mL^(-l);Na^(2+)-K^(2+) ATPase activities were 7.40±0.44,3.91±0.46,6.82±0.70;Ca^(2+)-Mg^(2+) ATPase activities were 7.94±0.52,4.24±0.59,7.19±0.58;the apoptosis rates were(3.44±0.32)%,(21.79±2.15)%,(8.92±0.70)%;the expression levels of p-AMPK protein were 0.35±0.02,0.93±0.09,0.41±0.04;the protein expression levels of p-PCC-1αwere 0.23±0.04,1.00±0.09,0.32±0.02;there were statistically significant differences in the

关 键 词：达格列净 钠葡萄糖共转运蛋白2抑制药 心力衰竭大鼠 心功能 线粒体能量代谢 

分 类 号：R97[医药卫生—药品]