Yang Min, Chen Chun-Yuan, Cai Zi-Li, Chen Bo-Lin, Cheng Liang, Li Hui
Department of Pediatrics, Central South University, Changsha, China.
Zhongguo Dang Dai Er Ke Za Zhi. 2011 Aug;13(8):669-73.
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.
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.
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).
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.
探讨病毒性心肌炎(VMC)小鼠心肌组织中基质金属蛋白酶-9(MMP-9)表达的动态变化及其在病毒性心肌炎发病机制中的意义。
通过向BALB/C小鼠注射柯萨奇病毒B3(CVB3)制备VMC模型。将注射不含病毒培养液的小鼠作为对照组。在注射后7、14、21和28天获取心脏组织并制成石蜡切片。采用苏木精-伊红染色和Masson染色观察心肌组织病理变化。用SABC免疫组织化学方法定量检测心脏组织中MMP-9、Ⅰ型胶原和Ⅲ型胶原的表达。
VMC模型组在第7天观察到MMP-9表达,第14天达到峰值,且在所有时间点均显著高于对照组(P<0.05)。与对照组相比,VMC模型组Ⅰ型胶原表达在第21天上调,并在第28天达到峰值(P<0.05)。VMC模型组Ⅲ型胶原表达在第28天显著高于对照组(P<0.05)。MMP-9表达与心肌组织病理评分呈正相关(r=0.832,P<0.05),与Ⅰ型胶原表达呈负相关(r=-0.791,P<0.05)。
MMP-9在VMC小鼠早期过度表达,并通过介导Ⅰ型胶原的降解代谢参与VMC的病理过程。它可能是导致心肌胶原重塑和心肌纤维化的重要因素。