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目的探讨TIMP-1mRNA表达在病毒性心肌炎小鼠心肌胶原重构中的作用及其与转化生长因子(TGF-β1)的关系。方法4周龄雄性BALB/c鼠腹腔接种0.1ml100TCID50CVB3m,周龄、性别相同小鼠为对照,分别于接种后3、7、9、14、21、28、56d断脊处死小鼠,心肌标本经常规制片,VG染色观察心肌组织胶原的改变,原位杂交观察TIMP-1mRNA和TGF-β1mRNA的表达,免疫组织化学观察TGF-β1的表达。结果感染后28d小鼠心肌组织血管周围胶原明显沉积,感染后56d心肌组织血管周围及心肌细胞间隙胶原沉积均明显增加;感染后7d可见TIMP-1mRNA表达,14～21d最为明显,此后减弱,直到56d。感染后3d可见TGF-β1mRNA及TGF-β1表达,7～21d最为明显,此后减弱,持续至感染后56d;TIMP-1mRNA和TGF-β1表达等级间存在正相关关系(P<0.001)。结论TGF-β1表达增加及其上调TIMP-1mRNA的表达可能在病毒性心肌炎心肌胶原重构中起重要作用。
Objective To investigate the role of TIMP-1 mRNA in cardiomyocyte collagen remodeling and its relationship with transforming growth factor-β1 (TGF-β1) in mice with viral myocarditis. Methods 4-week-old male BALB / c mice were inoculated intraperitoneally with 0.1ml100TCID50CVB3m, and the same age and sex mice as control. The mice were sacrificed at 3,7,9,14,21,28,56d after inoculation. The myocardial samples VG staining was used to observe the change of collagen in myocardial tissue. The expression of TIMP-1 mRNA and TGF-β1 mRNA was observed by in situ hybridization. The expression of TGF-β1 was observed by immunohistochemistry. Results The collagen pericardium of myocardium obviously deposited on the 28th day after infection, and the perivascular and myocardial interstitial collagen deposition in myocardium significantly increased on the 56th day after infection. The expression of TIMP-1 mRNA was observed on the 7th day after infection, 56d. The expression of TGF-β1 mRNA and TGF-β1 was observed 3d after infection, most obviously from 7 to 21 days, then weakened and continued until 56 days after infection. There was a positive correlation between TIMP-1 mRNA and TGF-β1 expression level (P <0.001). Conclusion The increased expression of TGF-β1 and its upregulation of TIMP-1 mRNA may play an important role in the remodeling of myocardial collagen in viral myocarditis.