慢性缺血性心力衰竭时心肌基质金属蛋白含量的变化

MMP_2 activity increase in an ovine model of chronic ischaemic heart failure

目的 :验证慢性缺血性心力衰竭时左心室扩张和重构与心肌基质金属蛋白酶 (MMPs)活性改变有关的假说。方法 :用重复多次冠状动脉内微球栓塞法对 11只羊造成中等程度慢性心力衰竭。在栓塞前和栓塞 6个月后用超声心动图测定心脏腔径及室壁厚度 ,用Mikro Millar压力传感导管测定左心室舒张末期压(LVEDP) ,左心室压力最大上升速率 (dP/dtmax) ,最大下降速率 (dP/dtmin) ,用左心室造影测定左心室射血分数(LVEF)。测定完上述参数后处死动物检测心脏MMPs活性并与 10只正常羊比较。用以明胶为底物的酶图法测定MMPs活性。结果 :与基础值相比 ,多次微球冠状动脉栓塞后 6个月 ,左心室舒张末期内径〔从 (4.0 0± 0 .4 1)～ (5 .30± 0 .36 )cm〕、左心室腔径 /室壁厚度比值〔从 (2 .30± 0 .31)～ (3.90± 0 .6 1)〕、左室舒张末期容积〔从(6 9.0 0± 17.5 4 )～ (12 3.2 0± 32 .5 5 )ml〕、LVEDP〔从 (7.80± 2 .6 1)～ (12 .90± 2 .15 )mmHg(1mmHg =0 .133kPa)〕均明显增高 (P <0 .0 1) ,而LVEF〔从 (5 6 .2 0± 8.2 9) %～ (33.80± 5 .88) % ,P <0 .0 1〕 ,LVdP/dtmax〔从(12 5 8± 2 32 )～ (988± 198)mmHg/s,P <0 .0 5〕 ,LVdP/dtmin〔从 (16 14± 4 97)～ (12 16± 2 79)mmHg/s,P <0 .0 5〕均明显下降。与?

Objective:The aim of this study was to test the hypothesis that the LV dilation and remodelling during the development of CHF is associated with the change of Matrix metalloproteinases (MMPs) zymographic activity.Methods:Eleven sheeps were developed into moderate chronic heart failure by sequential microembolisation and the hearts were studied for MMPs after echocardiographic and hemodynamic evaluation 6 months after the development of CHF and compared with 10 normal sheeps. MMPs activity was determined by gelatin zymography.Results:Compared with the baseline data, left ventricular(LV) end diastolic diameter 〔from( 4.00 ± 0.41 )～( 5.30 ± 0.36 )cm〕, the ratio of LV diameter and wall thickness 〔from( 2.30 ± 0.31 )～( 3.90 ± 0.61 )〕, LV end diastolic volume 〔from( 69.00 ± 17.54 )～( 123.20 ± 32.55 )ml〕, LV end diastolic pressure〔from( 7.80 ± 2.61 )～( 12.90 ± 2.15 )mmHg〕 increased significantly 6 months after the development of CHF (P< 0.01 ). While the LV ejection fraction 〔from( 56.20 ± 8.29 )%～( 33.80 ± 5.88 )%, P< 0.001 〕, LV dP/dt max 〔from(1258±232)～(988±198)mmHg, P< 0.05 〕 and LVdP/dt min 〔from(1614±497)～(1216±279)mmHg, P< 0.05 〕 decreased significantly. Three and half fold increase in LV myocardial MMP 2 zymographic activity against the substrate gelatin was observed in CHF sheep as compared with the normal sheep. There were no significant difference in MMP 1 and MMP 9 zymographic activity between the two groups.Conclusion:Increase in LV myocardial MMP 2 zymographic activity has been found in CHF sheep and may be partly responsible for the LV dilation and remodelling seen in this model of heart failure.