酮替芬对小鼠病毒性心肌炎的作用研究

目的研究肥大细胞膜稳定剂酮替芬对脑心肌炎病毒（EMCV）心肌炎的作用。方法4周龄DBA／2小鼠经腹腔接种EMCV制成病毒性心肌炎模型，评价灌胃给予酮替芬对小鼠病毒性心肌炎的作用。观察小鼠在接种EMCV后14d生存率的变化。小鼠心肌切片HE、Masson trichrome染色，观察心室肌坏死和炎症细胞浸润面积的变化。荧光定量RT—PCR检测小鼠心脏促炎细胞因子（IL-6、TNF—α）和肥大细胞蛋白酶类胰蛋白酶及糜蛋白酶（mMCP-4、mMCP-5、mMCP-6）mRNA表达。结果酮替芬治疗使小鼠的14d生存率明显改善（75％比25％，P〈0．01）；小鼠心脏／体重比值显著改善（P〈0．05）；小鼠左心室坏死和炎症细胞浸润面积明显减少（P〈0．05）；IL-6、TNF—α、mMCP－4、mMCP－5及mMCP－6mRNA的表达明显下调（P〈0．05）。结论酮替芬可改善EMCV心肌炎小鼠的心肌炎症和生存率，其作用机制可能与下词心肌促炎细胞因子和肥大细胞特异蛋白酶类胰蛋白酶和糜蛋白酶的表达有关。

The effect of ketotifen on viral myocarditis in mice

Objective This study was designed to examine the effect of ketotifen on viral myocaxditis in mice. Methods Four-week old DBA/2 mice were inoculated intrapefitoneally with EMCV. EMCV infected mice were administered orally with ketotifen. The 14-day survival of mice was observed. Pathological study was performed to evaluate necrosis areas and inflammatory infiltration in murine hearts, mRNA expression of cytokines, mast cell proteases （chymase and tryptase, including MCP-4, MCP-5, and MCP-6） were evaluated by quantitative RT-PCR. Results The 14-day survival of mice administered with ketotifen was significantly improved （75% vs 25%,P〈0.01 ）. The ratio of heart weight to boby weight was ameliorated by ketotifen （P〈0.05）. Ketotifen treatment significantly attenuated myocardial lesions （P〈0.05） and suppressed mRNA expression of IL-6,TNF-α, mMCP-4, mMCP-5, mMCP-6 in hearts （P〈0.05）. Conclusion Ketotifen can ameliorate murine viral myocarditis by suppressing the expression of deleterious cytokines and mast cell proteases.