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目的 评价基质金属蛋白酶(MMP)抑制剂强力霉素(Dox)对急性心肌梗死(AMI)大鼠左室非MI区心肌MMP-8和13、MMP组织型抑制剂(TIMP)-1和2的表达及胶原重构的影响。方法 将雌性SD大鼠于AMI术后24 h随机分为:AMI对照组和Dox(30 mg·kg-1·d-1)治疗组,并开始给药治疗。另设假手术组。上述各组再均随机分为1周、2周和4周3个疗程亚组。满疗程后处死大鼠,测定左室MI面积;以RT-PCR和Western印迹法测定非MI区两种MMP和TIMP的mRNA和蛋白表达;免疫组化染色测定非MI区Ⅰ/Ⅲ型胶原含量(CVF)。结果 MI面积在AMI对照和治疗组各时间点亚组间差异均无显著意义(42％-48％,均P>0.05)。与假手术组相比,AMI对照组的MMP-8和13蛋白表达在各时间亚组均显著增高(均P<0.05),mRNA表达则在1周和4周亚组均显著增高(均P<0.05);而TIMP-1 mRNA和蛋白表达仅在1周亚组时均显著增高(均P<0.05);TIMP-2 mRNA表达在各时间点亚组均显著增高(均P<0.05),而蛋白表达仅在2和4周亚组时均显著增高(均P<0.05);最后非MI区Ⅰ/Ⅲ型CVF在各时间亚组均显著升高(P<0.05-0.001)。与AMI对照组相比,Dox对大鼠AMI后MMP-8、13和TIMP-1、2 mRNA和蛋白表达的增强均有显著抑制作用(均P<0.05);使Ⅰ型CVF减少(P<0.01-0.001),但对Ⅲ型CVF于各时间点亚组均无显著影响。结论 MM
Objective To evaluate the effects of matrix metalloproteinase (MMP) inhibitor doxycycline (Dox) on myocardial MMP-8 and 13, tissue inhibitor of metalloproteinases (TIMP) -1 and 2 in non-MI myocardium of rats with acute myocardial infarction (AMI) Expression and Collagen Remodeling. Methods Female Sprague-Dawley rats were randomly divided into AMI control group and Dox (30 mg · kg-1 · d-1) treatment group 24 h after AMI. Another set of sham operation group. The above groups were randomly divided into three groups: one week, two weeks and four weeks. The rats were sacrificed after the full course of treatment to determine the area of left ventricular MI. The mRNA and protein expressions of two MMPs and TIMP in non-MI area were determined by RT-PCR and Western blotting. The content of collagen type Ⅰ / Ⅲ in non-MI area (CVF). Results There was no significant difference in MI area between the subgroups of AMI control group and treatment group at any time point (42% -48%, all P> 0.05). Compared with the sham-operation group, the expression of MMP-8 and 13 protein in AMI control group was significantly increased in all sub-groups (all P <0.05), and the mRNA expression in sub-groups was significantly higher in both sub-groups <0.05). TIMP-1 mRNA and protein expression were significantly increased only in 1-week subgroup (all P <0.05); TIMP-2 mRNA expression was significantly increased in all subgroups at all time points (all P <0.05) (P <0.05). However, the expression of type I / III CVF in non MI group was significantly increased at each time subgroup (P <0.05-0.001). Compared with AMI control group, Dox significantly inhibited the expression of MMP-8, 13 and TIMP-1,2 mRNA and protein in AMI rats (all P <0.05), and decreased the type I CVF (P < 0.01-0.001), but there was no significant effect on type III CVF subgroups at all time points. Conclusion MM