盐酸多西环素对心梗大鼠心肌基质金属蛋白酶的影响

Effects of Doxycycline on Matrix Metalloproteinases in Rats after Myocardial Infarction

目的:观察盐酸多西环素对心肌梗死后心肌基质金属蛋白酶-9(MMP-9)的影响及对心室重构的作用机制。方法:选择健康雌性Wistar大鼠45只,随机分为3组。实验组和对照组结扎左冠状动脉,假手术组只挂线不结扎冠状动脉。对照组和假手术组术后给予等量生理盐水灌胃,实验组术后给予盐酸多西环素灌胃。3组大鼠于手术后7d处死。HE染色观察左室形态变化,免疫组化SP法检测心肌组织MMP-9表达。计算机图像分析系统半定量分析。结果:(1)对照组和实验组均可见心肌梗死发生,但2组梗死面积差别无统计学意义(P>0.05);2组梗死区MMP-9表达均增强,且对照组表达更明显。(2)对照组和实验组均较假手术组左室腔面积扩大,且对照组左室腔面积更大,梗死区厚度更薄。结论:急性心肌梗死后1周的大鼠梗死区MMP-9表达增强,并发生左室重构。盐酸多西环素可能通过抑制梗死心肌组织中MMP-9的表达而抑制心室重构。

Objective： To observe the effects of doxycycline on matrix metalloproteinases-9 （MMP-9） and ventricular remodeling （VRM） in rats after myocardial infarction and discuss its mechanisms. Methods： Forty-five healthy female Wistar rats were randomly allocated into three groups. The left coronary artery of rats was ligated in the experimental group and the control group, doxycycline 10 mg/（kg· d） in one milliliter saline were given to the rats in the experiment group by gastric lavage postoperation. On the other hand, rats in the sham-operated and control groups received one milliliter saline by tragastric lavage. All rats were killed seven days after surgery. The changes of left ventricular structure were observed by HE staining and the expression of MMP-9 in myocardial ceils was examined by immunohistochemical methods. All the results were scanned and semi-quantitatively analyzed by computer image. Results： （1）Infarction was observed in experimental and control group, but the difference was not statistical （P 〉 0.05）. The expression of MMP-9 increased in the infracted zone in both groups and it was more significant in the control group. （2）The left ventricular cavity area in the experiment and the control group increased compared with the sham-operate group, moreover, the infracted zone got thinner and the left ventriculer cavity area was more spacial in the control group. Conclusion： The expression of MMP-9 in infracted zone of rats is strong and left ventricular remodeling happen one week after AMI. Doxycycline may inhibit ventricular remodeling by inhibiting the expression of MMP-9 in myocardial tissue.