达格列净对急性心肌梗死后大鼠的心肌电活动影响的研究

Effect of Dapagliflozin on myocardial electrical activity in rats after acute myocardial infarction

目的探讨达格列净对急性心肌梗死(acute myocardial infarction,AMI)后大鼠心室结构及心室肌电活动稳定性的影响。方法将健康成年Sprague-Dawley(SD)雄性大鼠24只随机分为三组:正常对照组(NC组,8只)、安慰剂组(PB组,8只)达格列净组(DAPA组,8只)。NC组、PB组给予1 ml·kg^(-1)·d^(-1)生理盐水灌胃处理,DAPA组给予1 ml·kg^(-1)·d^(-1)达格列净灌胃处理,一天一次。给药14天后,三组大鼠经外科开胸手术,剪开心包,NC组只观察,PB组和DAPA组通过结扎前降支动脉制备AMI模型,建模成功后即行超声心动图测量左心室舒张末期内径(left ventricular end diastolic dimension,LVEDD)、左心室收缩末期内径(left ventricular end-systolic diameter,LVESD)和左心室射血分数(left ventricular ejection fraction,LVEF);通过SiS2程序性刺激评估三组大鼠左心室有效不应期(1eft ventricular effective refractory period,LVERP)、SiS连续刺激测定心室颤动阈值(ventricular fibrllation threshold,VFT);利用Masson染色检测左心室心肌纤维化程度。结果分析比较三组小鼠心动超声各指标变化情况:①LVERP:PB组、DAPA组较NC组明显缩短[PB组比NC组(9.13±1.04)ms比(17.86±2.03)ms,P<0.01;DAPA组比NC组(14.37±1.25)ms比(17.86±2.03)ms,P<0.01];然而DAPA组较PB组增加[(14.37±1.25)ms比(9.13±1.04)ms,P<0.01]。②VFT:PB、DAPA组的VFT较NC组均明显降低[PB组比NC组(2.88±1.29)V比(10.07±0.98)V,P<0.01;DAPA组比NC组(7.44±1.03)V比(2.88±1.29)V,P<0.01]。③LVEDD:PB组LVEDD较NC组明显增加[(10.00±1.12)mm比(6.10±1.79)mm,P<0.05];DAPA组LVEDD较PB组明显降低[(7.98±0.97)mm比(10.00±1.12)mm,P<0.05]。④LVESD:PB组、DAPA组LVESD均较NC组增加[PB组比NC组(8.01±0.76)mm比(3.25±1.82)mm,P<0.05;DAPA组比NC组(5.94±0.82)mm比(3.25±1.82)mm,P<0.05];DAPA组LVESD较PB组明显降低[(5.94±0.82)mm比(8.01±0.76)mm,P<0.05]。⑤LVEF:PB组、DAPA组LVEF均较NC组显著下降[PB组比NC组(23.92±2.04)%比(49.75±2.07)%,P<0.05;DAPA组比NC组(35.85±2.15)%比(49.75±2.07)%,P<0.05];进一步比较发现,DAPA组较PB组增加[(35.85±2.15)%比(23.92±2.04)%,P<0.05]。⑥左心室心肌纤维化程度:PB组、DAPA组左心室心肌纤维化程度均较NC组增加[PB组比NC组(45.69±3.19)%比(30.07±2.19)%,P<0.05;DAPA组比NC组(35.13±2.17)%比(30.07±2.19)%,P<0.05];进一步比较发现,DAPA组较PB组明显减小[(35.13±2.17)%比(45.69±3.19)%,P<0.05]。结论达格列净可以增加AMI大鼠左心室的电活动稳定性,降低左心室纤维化,改善心室重塑。

Objective To investigate the effect of Dapagliflozin on myocardial electrical activity after acute myocardial infarction(AMI)in rats.Methods Twenty-four healthy adult Sprague-Dawley rats were randomly divided into three groups:normal control group(NC group,n=8),placcbo group(PB group,n=8)and Dapagliflozin group(DAPA group,n=8).The NC group was not treated,the PB group was given intragastric administration of normal saline at the dose of 1 ml·kg^(-1)·d^(-1)and the DAPA group was given intragastric administration of Dapagliflozin at the dose of 1 ml·kg^(-1)·d^(-1)for 14 days.Then,the rats of all groups were treated with surgical thoracotomy,AMI model were established by ligating the anterior descending artery in all rats except for the NC group.The left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD)and left ventricular ejection fraction(LVEF)were measured by echocardiography.The left ventricular effective refractory period(LVERP),the ventricular fibrillation threshold(VFT)were recorded via SiS2 and SIS2 programmed stimulation.Masson staining was used to observe the degree of left ventricular myocardial fibrosis.Results(1)LVERP:Compared with NC group,the LVERP of PB group,DAPA group was significantly decreased[PB group vs.NC group(9.13±1.04)ms vs.(17.86±2.03)ms,P<0.01;DAPA group vs.NC group(14.37±1.25)ms vs.(17.86±2.03)ms,P<0.01];however the LVERP of DAPA group was increased compared with PB group[(14.37±1.25)ms vs.(9.13±1.04)ms,P<0.01].(2)VFT:Compared with NC group,the VFT of PB group,DAPA group was significantly decreased[PB group vs.NC group(2.88±1.29)V vs.(10.07±0.98)V,P<0.01;DAPA group vs.NC group(7.44±1.03)V vs.(2.88±1.29)V,P<0.01].(3)LVEDD:Compared with NC group,the LVEDD of PB group was significantly increased[(10.00±1.12)mm vs.(6.10±1.79)mm,P<0.05];compared with PB group,the LVEDD of DAPA group was significantly increased[(7.98±0.97)mm vs.(10.00±1.12)mm,P<0.05].(4)LVESD:Compared with NC group,the LVESD of PB group,DAPA group was significantly increased[PB group vs.NC group(8.01±0.76)mm vs.(3.25±1.82)mm,P<0.05,DAPA group vs.NC group(5.94±0.82)mm vs.(3.25±1.82)mm,P<0.05];compared with PB group,the LVESD of DAPA group was significantly decreased[(5.94±0.82)mm vs.(8.01±0.76)mm,P<0.05].(5)LVEF:Compared with NC group,the LVEF of PB group,DAPA group was significantly decreased[PB group vs.NC group(23.92±2.04)%vs.(49.75±2.07)%,P<0.05;DAPA group vs.NC group(35.85±2.15)%vs.(49.75±2.07)%,P<0.05];compared with PB group,the LVEF of DAPA group was significantly increased[(35.85±2.15)%vs.(23.92±2.04)%,P<0.05].(6)Left ventricular myocardial interstitial collagen:Compared with the NC group,the left ventricular myocardial interstitial collagen of the PB and DAPA groups were significantly increased[PB group vs.NC group(45.69±3.19)%vs.(30.07±2.19)%,P<0.05;DAPA group vs.NC group[(35.13±2.17)%vs.(30.07±2.19)%,P<0.05];compared with the PB group,the left ventricular myocardial interstitial collagen of the DAPA groups were significantly decreased[(35.13±2.17)%vs.(45.69±3.19)%,P<0.05].Conclusion Dapagliflozin increased the stability of myocardial electrical activity in AMI rats and prevented left ventricular fibrosis and improved left ventricular remodel.