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目的:探讨抑制mi R-21可否减轻CVB3诱导的BALB/c小鼠心脏微血管损伤,阻断致病因子向靶器官迁移,从而减轻靶器官组织病变。方法:3~4周龄雄性BALB/c小鼠CVB3腹腔注射后饲养1周诱导急性病毒性心肌炎(VMC)模型;BALB/c小鼠每月腹腔注射CVB3 1次共饲养3个月,诱导为慢性VMC模型。注射CVB3同时尾静脉注射抗mi R-21质粒以敲低mi R-21表达。结果:急性VMC小鼠外周血mi R-21表达增加,心肌Bcl-2和CVB3-VP1表达增加。小鼠体内注射anti-mi R-21质粒后,外周血mi R-21表达降低,心肌caspase-3活性和CVB3-VP1表达下降,Bcl-2表达增加,HE染色心肌组织及心脏微血管病变减轻,TUNEL染色心肌细胞凋亡减少。慢性VMC小鼠心肌胶原表达增加,微血管密度减少,心功能下降。敲低mi R-21增加慢性VMC小鼠心肌微血管密度,减少胶原沉积,改善小鼠心功能。体外过表达mi R-21诱导CMVECs凋亡,减少心脏微血管新生。结论:靶向抑制mi R-21可能通过抑制CMVECs凋亡,阻断致病因子向靶器官迁移,降低心肌病毒载量、减轻心肌炎心肌病变。慢性VMC小鼠中,可能是通过减少胶原沉积、减轻心肌纤维化,增加微血管新生,改善心功能。因此,mi R-21可能是治疗病毒性心肌炎的新靶点。
OBJECTIVE: To investigate whether inhibiting mi R-21 can reduce CVB3-induced cardiac microvascular injury in BALB / c mice and block the migration of pathogenic agents to target organs, thereby reducing the target organ damage. Methods: Acute viral myocarditis (VMC) model was induced by intraperitoneal injection of CVB3 in male BALB / c mice (3 to 4 weeks old) for 1 week. BALB / c mice were intraperitoneally injected with CVB3 once a month for 3 months to induce Chronic VMC model. Anti-mi R-21 plasmid was injected into the tail vein intravenously to knock down mi R-21 expression. Results: The expression of mi R-21 and the expression of Bcl-2 and CVB3-VP1 in peripheral blood of acute VMC mice increased. After the mice were injected with anti-mi R-21 plasmid, the expression of mi R-21 in the peripheral blood decreased, the activity of caspase-3 and the expression of CVB3-VP1 decreased, the expression of Bcl-2 increased, the myocardial tissue and cardiac microangiopathy lessened, TUNEL-stained myocytes apoptosis decreased. Chronic VMC mice increased myocardial collagen expression, reduced microvessel density, decreased cardiac function. Knockdown of mi R-21 increases myocardial microvessel density in chronic VMC mice, reduces collagen deposition and improves cardiac function in mice. Overexpression of mi R-21 in vitro induced apoptosis of CMVECs and decreased cardiac microangiogenesis. Conclusion: Targeted inhibition of mi R-21 may inhibit the apoptosis of CMVECs, block the migration of pathogenic factors to target organs, decrease the viral load of myocardium and relieve the myocarditis. In chronic VMC mice, it is possible to improve cardiac function by reducing collagen deposition, reducing myocardial fibrosis, increasing angiogenesis and angiogenesis. Therefore, mi R-21 may be a new target for the treatment of viral myocarditis.