基质金属蛋白酶抑制剂强力霉素对大鼠急性心肌梗死后左心室重构和功能的影响

The Beneficial Effect of Matrix Metalloproteinase Inhibitor Doxycycline on the Prevention of Left Ventricular Remodeling After Acute Myocardial Infarction in Rat

目的 :评价基质金属蛋白酶抑制剂强力霉素对大鼠急性心肌梗死 (AMI)后左心室重构和功能的影响。方法 :AMI术后 2 4小时存活的 12 7只雌性SD大鼠随机分成AMI组 64只和强力霉素组 63只 [3 0mg/(kg·d) ] ,并开始给药治疗 ;另设 3 0例对照作为假手术组。上述各组再随机分配 ,分别观察 1周、2周和 4周 3个疗程。满疗程后均以导管法行血流动力学测定、心脏标本固定和病理分析。最终 94只大鼠获完整资料。结果 :梗死面积在AMI组和强力霉素组 3个疗程间均无显著差异 ( 4 2 %～ 48% ,P均 >0 0 5 )。与假手术组相比 ,AMI组的左心室舒张末压、实际和相对重量在各时间点均显著增加 (P <0 0 5～ 0 0 0 1) ,且左心室舒张末压在 4周比 1和 2周时升高更显著 (P均 <0 0 1) ;而左心室内压最大上升和下降速率及其校正值 (左心室内压最大上升和下降速率 /左心室收缩压 )在 4周时均显著降低 (P均 <0 0 0 1)。与AMI组相比 ,强力霉素组的左心室舒张末压在各时间点均显著降低 (P<0 0 5～ 0 0 0 1) ;实际和相对重量在 4周时均显著减轻 (P <0 0 5～ 0 0 0 1) ;而左心室内压最大上升和下降速率的校正值在 4周时均显著升高 (P <0 0 5～ 0 0 1)。结论

Objectives:To assess the effect of matrix metalloproteinase inhibitor doxycycline on the prevention of left ventricular remodeling after acute myocardial infarction (AMI) in rat.Methods:AMI were conducted by ligating left coronary artery in female SD rats. 24 hours after the procedure,the 127 survival rats were randomized to AMI controls ( n =64) and doxycycline treatment group [30 mg/(kg·d),n =63],with the drug therapy initiated immediately. Also,sham-operated rats ( n =30) were randomly selected to serve as noninfarction controls. Then,the rats in each of the above mentioned 3 groups were further divided,and were observed or treated for 1,2 or 4 weeks respectively. After the completion of treatment,hemodynamic studies were performed. The heart of rat was fixed and analyzed pathologically. Exclusive of the dead rats and the hearts with the MI size<35% or >%,complete experimental data were obtained in 97 rats. The number of rats for each treatment period in each group was 9～12.Results:There was no significant difference in MI sizes between AMI controls and doxycycline group for each of the 3 treatment periods(42%～48%,all p >0.05). Compared with sham operated rats,left ventricular (LV) end diastolic pressure (LVEDP) and LV absolute weight (LVAW) and relative weight (LVRW) were significantly increased in AMI controls at all 1,2 and 4 weeks after AMI( p <0.05～0.001),with LVEDP elevated significantly more at 4 weeks than at 1 and 2 weeks after AMI(all p < 0.01);whereas ±dp/dt and its corrected value by LV systolic pressure (±dp/dt/LVSP) were all significantly reduced only at 4 weeks after AMI(all p <0.001). Compared with AMI controls,LVEDP was significantly reduced at all 1,2 and 4 weeks after AMI in doxycycline group( p <0.05～0.001),with LVAW and LVRW both significantly reduced ( p <0.05～0.001)and-dp/dt and ±dp/dt/LVSP all significantly raised only at 4 weeks after AMI( p <0.05～0.01).Conclusion:Doxycycline can effectively prevent left ventricular remodeling and improve its systolic and diastolic functions after AMI in rat.