金属蛋白酶-9及其抑制物-1在实验性心动过速性心肌病中的变化

Changes in metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 during tachycardia-induced cardiomyopathy in dogs

目的观察心动过速性心肌病(TIC)时金属蛋白酶(MMP)-9及其抑制剂(TIMP)-1的变化。方法对11只犬采用快速右房起搏建立TIC模型组,6只犬作假手术组(对照组)。应用超声心动图和心导管检查测量在窦性心律下的血流动力学数据。应用电子显微镜观察左室组织的超微结构改变。MMP-9及TIMP-1的相对变化通过免疫印迹法获得。结果8周后,与对照组相比,TIC组犬左室舒张末期容积及收缩末期容积均显著增加(P<0.05);左室射血分数在起搏1周后显著减小(P<0.05)。左室压力最大上升速率显著下降,最大下降速率绝对值显著下降(P<0.05和0.001),左室舒张末期压显著增大,左室松弛时间常数明显延长(P<0.05),二尖瓣血流频谱A波峰值流速和E波峰值流速均显著减小。心肌细胞超微结构发生变化,同时MMP-9增加,TIMP-1减少。结论快速右房起搏可制造TIC模型,TIC时MMP-9增加,TIMP-1减少。

Objective To investigate the variation in metalloproteinase（MMP） -9 and tissue inhibitor of metalloproteinase （TIMP）-1 levels during tachycardia-induced cardiomyopathy （TIC）. Methods Canine models of TIC were established by rapid right atrial pacing at 350 -400 beats per rain for 8 weeks in 11 dogs, with another 6 clogs as control group. Echocardiography, left ventricular pressure and its first derivation with time were acquired in sinus rhythm. Uhrastructural changes in left ventricular tissue were observed by transmission electron microscope. The relative abundance of MMP-9 and TIMP-1 was studied by immunoblotting. Results After 8 weeks of rapid pacing, in the TIC group left ventricular end-diastolic volume and end-systolic volume were decreased （ P 〈 0.05 ） ; The left ventricular ejection fraction was significantly decreased after 1 week of pacing （P 〈 0.05 ） ;The TIC group had decreased dp/dtmax （P 〈 0.05 ） ;The left ventricular relaxation time constant （τ） was prolonged （P 〈0.05 ） ;Left ventricular end-diastolic pressure was significantly increased （P 〈 0.05 ） ; and - dp/dtmax was significantly decreased （ P 〈 0,001 ） compared with the control group ; The peak A wave velocity and the peak E velocity of mitral valvular blood-flow spectrum decreased after pacing for 8 weeks. Uhrastru ctural changes in the cell seen after 8 weeks of pacing,and MMP-9 was significantly higher,while TIMP-1 was decreased, Conclusions Canine models of TIC can be established by rapid right atrial pacing . MMP-9 is increased and TIMP-1 is decreased after 8weeks of pacing. lloproteinase