病毒性心肌炎小鼠心肌基质金属蛋白酶-9的动态变化及意义

Expression of matrix metalloproteinase-9 in myocardium of mice with viral myocarditis

摘要:

目的：探讨基质金属蛋白酶-9（MMP-9）在病毒性心肌炎（VMC）小鼠发病过程中的动态变化及意义。方法：以柯萨奇病毒 B3 感染 BALB/C 小鼠建立 VMC 模型，腹腔注射 0.1 mL不含病毒的培养液的小鼠作为对照组。造模后 7 d、14 d、21 d、28 d取心肌组织作石蜡切片，行苏木精-伊红和 Masson 染色观察病理改变，免疫组化（SABC法）检测心肌MMP-9及Ⅰ、Ⅲ型胶原表达。结果：模型组 MMP-9 于 7 d 可见表达，14 d 达高峰（P<0.05），各时间点 MMP-9 表达均高于对照组（P<0.05）；Ⅰ型胶原于 21 d 表达上调，28 d 表达最高（P<0.05），21 d 和 28 d 表达高于对照组（P<0.05）；Ⅲ 型胶原于28 d 表达上调并高于对照组（P<0.05）；MMP-9 与心肌病理积分呈正相关（r=0.832，P<0.05），与 Ⅰ 型胶原呈负相关（r=-0.791，P<0.05）。结论：VMC 小鼠心肌 MMP-9 在早期即表达增高；MMP-9 可能通过介导 Ⅰ 型胶原的降解代谢而参与 VMC 的病理过程，是导致 VMC 胶原重构和心肌纤维化的重要因素之一。

Abstract:

OBJECTIVE: To investigate the dynamic changes of expression of matrix metalloproteinases-9 in myocardium of mice with viral myocarditis (VMC) and its significance in the pathogenesis of viral myocarditis. METHODS: VMC model was prepared by an injection of CVB3 in BALB/C mice. The mice receiving an injection of culture solution without virus were used as the control group. Cardiac tissues were obtained 7, 14, 21 and 28 days after injection and made into paraffin sections. Myocardial histopathologic changes were observed by hematoxylin-eosin staining and Masson staining. The expression of MMP-9, type I collagen and type III collagen in cardiac tissues were quantified by SABC immunohistochemical method. RESULTS: The expression of MMP-9 in the VMC model group was observed on the 7th day, reached a peak on the 14th day, and was significantly higher than that in the control group at all time points (P<0.05). Compared with the control group, the expression of type I collagen in the VMC model group was up-regulated on the 21st day and reached a peak on the 28th day (P<0.05). The expression of type III collagen in the VMC model group was significantly higher than that in the control group on the 28th day (P<0.05). The expression of MMP-9 was positively correlated with myocardial histopathologic scores (r=0.832, P<0.05) and negatively correlated with type I collagen expression (r=-0.791, P<0.05). CONCLUSIONS: MMP-9 is over-expressed at the early stage in VMC mice, and participates in the pathological process of VMC through mediating the degradation metabolism of type I collagen. It may be an important factor that leads to myocardial collagen remodeling and myocardial fibrosis.