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目的探讨基质金属蛋白酶(matrix metalloproteinase,MMP)-9及组织抑制因子(tissue inhibitors ofmetalloproteinase,TIMP)-1在老年犬持续性心房颤动(房颤)心房肌组织中表达变化及其与心房颤动及纤维化发生的关系。方法健康比格犬18只随机分为成年、老年窦性心律组各5只、成年、老年持续性房颤组各4只。采用Masson三色法染色,计算胶原容积分数以测定纤维化程度,采用RT-PCR检测左心房MMP-9及TIMP-1的mRNA水平表达情况,采用蛋白质印迹法测定其蛋白水平表达情况。结果与成年窦性心律组比较,其余3组心房肌组织纤维化程度明显增高(P<0.01);TIMP-1mRNA表达水平下降(P<0.05),MMP-9蛋白表达水平升高(P<0.01),TIMP-1蛋白表达水平下降(P<0.01);老年窦性心律组及老年持续性房颤组MMP-9mRNA表达水平较成年窦性心率组升高(P<0.05);与成年持续性房颤组比较,老年持续性房颤组纤维化程度增加,胶原容积分数明显增高(P<0.05),TIMP-1蛋白表达水平下降(P<0.01)。结论心房组织中MMP-9和TIMP-1基因表达失衡可能是影响胶原代谢、造成增龄性心房颤动时心房肌纤维化的分子机制之一,与增龄性心房颤动的发生和持续有关。
Objective To investigate the expression changes of matrix metalloproteinase (MMP) -9 and tissue inhibitor of metalloproteinase (TIMP) -1 in atrial fibrillation (AF) atrial fibrillation in elderly dogs and its relationship with atrial fibrillation and fibrosis The relationship that happened. Methods Eighteen healthy beagle dogs were randomly divided into five groups: adult and old sinus rhythm group, and four adult and elderly persistent AF groups. Masson’s trichrome staining was used to calculate collagen volume fraction to determine the degree of fibrosis. RT-PCR was used to detect mRNA expression of MMP-9 and TIMP-1 in left atrium. Protein expression was measured by Western blot. Results Compared with the adult sinus rhythm group, the fibrosis of the other three groups was significantly increased (P <0.01); the expression of TIMP-1 mRNA was decreased (P <0.05); the expression of MMP-9 protein was increased (P <0.01). The expression of MMP-9 mRNA in elderly sinus rhythm group and elderly persistent AF group was higher than that in adult sinus rhythm group (P <0.05) Compared with the AF group, the fibrosis degree, the collagen volume fraction (P <0.05) and the TIMP-1 protein level decreased in the elderly patients with persistent AF (P <0.01). Conclusion Unbalanced expression of MMP-9 and TIMP-1 in atrial tissue may be one of the molecular mechanisms that affect collagen metabolism and cause atrial fibrosis in patients with age-related atrial fibrillation, which is related to the occurrence and persistence of age-related atrial fibrillation.