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目的:探讨大鼠心肌梗死后心肌间质基质金属蛋白酶-2(MMP-2)及转化生长因子-β1(TGF-β1)的表达与心室重塑的关系及米诺环素的干预影响。方法:结扎SD大鼠冠状动脉前降支建立急性心肌梗死模型,随机分成心肌梗死对照组和米诺环素(30mg·kg-1.d-1)治疗组,2组又随机分为1、2和4周亚组;另设假手术组。应用免疫组化方法测定胶原的表达。用逆转录-聚合酶链反应法及免疫组化方法检测MMP-2、TGF-β1mRNA和蛋白表达情况。结果:与假手术组相比,心肌梗死对照组MMP-2、TGF-β1的mRNA表达在各亚组明显升高(均P<0.05),各亚组MMP-2、TGF-β1蛋白表达也均增高(均P<0.05),非梗死区Ⅰ/Ⅲ胶原比例在2周和4周随之升高(均P<0.05)。而米诺环素治疗组MMP-2mRNA和蛋白表达在1、2和4周亚组,TGF-β1mRNA和蛋白表达在1、2周亚组,均较心肌梗死对照组显著降低(均P<0.05),Ⅰ/Ⅲ胶原比例在2周和4周亚组也显著降低(均P<0.05)。结论:大鼠心肌梗死后心肌间质内MMP-2、TGF-β1的表达增高,非梗死区Ⅰ/Ⅲ胶原比例上升,是心室重塑发生发展的重要机制。米诺环素可通过抑制MMP-2、TGF-β1的表达,逆转Ⅰ/Ⅲ胶原比例改善心肌梗死后心室重塑。
Objective: To investigate the relationship between the expression of matrix metalloproteinase-2 (MMP-2) and transforming growth factor-β1 (TGF-β1) and ventricular remodeling after myocardial infarction in rats and the effect of minocycline intervention. Methods: Acute myocardial infarction (AMI) model was established by ligating the anterior descending coronary artery of SD rats. The models were randomly divided into 3 groups: myocardial infarction control group and minocycline (30mg · kg-1.d-1) 2 and 4 weeks subgroups; another sham group. The expression of collagen was measured by immunohistochemistry. The expression of MMP-2 and TGF-β1 mRNA and protein were detected by reverse transcription-polymerase chain reaction and immunohistochemistry. Results: Compared with sham operation group, the mRNA expression of MMP-2 and TGF-β1 in myocardial infarction group was significantly increased in all subgroups (all P <0.05). The expression of MMP-2 and TGF- (All P <0.05). The proportion of collagen Ⅰ / Ⅲ in non-infarcted area increased at 2 weeks and 4 weeks (all P <0.05). Compared with myocardial infarction control group, the expression of MMP-2mRNA and protein in minocycline group was significantly lower at 1, 2, and 4 weeks (P <0.05) ), And the ratio of collagen Ⅰ / Ⅲ was significantly lower in subgroups at 2 weeks and 4 weeks (all P <0.05). CONCLUSION: The expression of MMP-2 and TGF-β1 in myocardial interstitium increases after myocardial infarction in rats, and the proportion of collagen Ⅰ / Ⅲ increases in non-infarcted area. It is an important mechanism of ventricular remodeling. Minocycline can improve ventricular remodeling after myocardial infarction by inhibiting the expression of MMP-2 and TGF-β1 and reversing the ratio of collagen Ⅰ / Ⅲ.