Phenytoin promotes collagen deposition and activity of matrix metalloproteinases in ventricle in rat after experimental myocardial infarction
- VernacularTitle:苯妥英钠促进心肌梗死后大鼠心室基质金属蛋白酶活性及胶原沉积
- Author:
Yong ZHU
;
Yuming LI
;
Xin ZHOU
- Publication Type:Journal Article
- Keywords:
phenytoin;
myocardial infarction;
matrix metalloproteinase;
collagen;
ventricular remodeling
- From:
Basic & Clinical Medicine
2006;0(10):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanisms of phenytoin accelerating healing process.Methods Adult male Wistar rats that survived ligatation of the left coronary artery were randomized to phenytoin group or operation control and compared to sham-operated rats.The time-dependent proteolytic activity of MMP-2 and MMP-9 were detected by gelatin zymography.Picrosirius red staining plus polarized light micrscopy was used for qualitative and quantitative analysis of collagen include collagen volume fraction(CVF) and ratio of typeⅠ/Ⅲ collagen.In addition,infarct thickness and myocyte cross-sectional area were also evaluated by image analysis.Results Fourteen days after myocardial infartion(MI),phenytoin reduced infarct wall thinning.Compared with control group,the rats received phenytoin had less myocyte cross-sectional area.Two weeks after MI,CVF in two groups both had significantly dynamic increase and phenytoin accelerated the change.In contrast to control group,ratio of typeⅠto type Ⅲ collagen in phenytoin increased more quickly.Apart from these results,phenytoin did little to CVF in non-infarcted region.Analysis of MMPs activity in myocardial extracts by zymography demonstrated that infarction-induced expression of proMMPs and active MMPs was both upregulated in phenytoin group and operation control.We found that after MI,MMP-9 activity increased as early as 1 day and reached a maximum then gradually descended,whereas MMP-2 began to increase rapidly and remain elevated for up to 14 days thereafter.Phenytoin seemed toenhance expression of MMP-2 and MMP-9.1 day after MI,active MMP-9 in phenytoin group expressed an increasing trendency compared to MI control.Conclusion Phenytoin can attenuate the degree of post-infarction left ventricular dilation and expansion of the infarct during the early phase of MI healing.MMP-2 and MMP-9 enhanced by phenytoin probably played a prominent role.
