干扰素-λ2对急性病毒性心肌炎小鼠凋亡相关蛋白的研究

Effect of IFN-λ2 on apoptotic protein in the myocardium in mice with viral myocarditis

摘要:

目的：干扰素-λ（IFN-λ)广泛存在于人体各组织中，目前研究发现其具有抗病毒、抗肿瘤等作用。但其是否能用于治疗病毒性心肌炎尚缺乏相关报道。探讨IFN-λ2在病毒性心肌炎（VMC）早期的作用，为IFN-λ2 是否能应用于临床治疗或预防VMC提供实验室依据。方法：采用腹腔注射柯萨奇B3（CVB3）病毒的方法制造病毒性心肌炎小鼠模型。实验分3组：空白对照组、病毒组、IFN-λ2 治疗组。空白对照组给予腹腔注射等量的PBS培养液，记为第0天；IFN-λ2治疗组从第1天开始，连续5 d每天经背部皮肤不同点给予小鼠IFN-λ2 400 ng （0.1 mL），空白对照组和病毒组则每天以同样方法给予等量生理盐水。死亡小鼠从组中剔除。9 d后处死所有存活小鼠。检测各组小鼠心脏的病理改变。采用免疫组织化学技术检测各组小鼠心脏组织中凋亡相关蛋白Bcl-2 及Bax的表达。结果：①病毒组心肌病理评分要高于空白对照组及IFN-λ2治疗组。 ②免疫组化结果显示正常心肌组织有少量Bcl-2及Bax的表达，病毒组较空白对照组Bcl-2表达减少、Bax表达明显增加(P<0.01)；IFN-λ2治疗组较病毒组Bcl-2表达增加、Bax表达减少(P<0.01) 。结论：INF-λ2 能减轻柯萨奇病毒所致心肌炎小鼠的心肌病理改变，能抑制小鼠心肌细胞凋亡，对VMC小鼠的心肌细胞具有保护作用。［中国当代儿科杂志，2009，11（4）：296-300］

Abstract:

OBJECTIVE: INF-λ has anti-viral and anti-tumor activities. Its application in viral myocarditis (VMC) has not been reported. This study investigated the role of INF-λ in acute VMC in mice. METHODS: Forty mice were randomly divided into three groups: VMC (n=15), IFN-λ2-treated VMC (n=15) and control (n=10). VMC was induced by an intraperitoneal injection of Coxsackievirus B3 (CVB3).The control group was intraperitoneally injected with 2% PBS. The IFN-λ2-treated VMC group was administered with 400 ng IFN-λ2 (0.1 mL) by subcutaneous injections daily, for 5 days. The control and the VMC groups were given equal amount of nomal saline.The surviving mice were sacrificed 9 days after IFN-λ2 treatment. The pathological changes of heart tissues were examined under a light microscope. Bcl-2 and Bax expression in heart tissues was determined by immunohistochemistry. RESULTS: The control group presented normal heart tissues. The INF-λ2-treated VMC group showed significantly a lower pathological score (1.5±0.5) than the untreated VMC group (2.8±0.8) (P<0.01). Bcl-2 expression decreased (P<0.01), in contrast, Bax expression increased (P<0.01) in the untreated VMC group compared with that in the control group. INF-λ2 treatment resulted in an increased Bcl-2 expression (P<0.01) and a decreased Bax expression (P<0.01) compared to the untreated VMC group. CONCLUSIONS: INF-λ2 may alleviate myocardial injuries and inhibit cardiomyocytic apoptosis, thus providing protective effects on myocardial cells in mice with acute VMC.［Chin J Contemp Pediatr, 2009, 11 (4):296-300］