Department of Cardiovascular Medicine Kyoto University Graduate School of Medicine, Kyoto, Japan.
J Inflamm (Lond). 2010 Aug 4;7:39. doi: 10.1186/1476-9255-7-39.
We showed that mast cells played a critical role in the progression of heart failure induced by pressure overload and viral myocarditis in mice. In this study, we investigated the effect of cetirizine, a selective H1 receptor antagonist, on experimental viral myocarditis induced by encephalomyocarditis (EMC) virus.
Four-week-old inbred male DBA/2 mice were inoculated intraperitoneally with 10 plaque-forming units (pfu) of the EMC virus. Cetirizine was administered orally at a dose of 1 or 10 mg/kg per day for the survival study, and 1 mg/kg for the histologic and gene expression studies, beginning on the day of viral inoculation.
Cetirizine improved survival dose dependently. Heart weight to body weight ratio was significantly decreased in mice treated with cetirizine. The area of myocardial necrosis was significantly smaller in the hearts of mice treated with cetirizine compared with controls. Gene expressions of tumor necrosis factor, interleukin 6, and metalloproteinase 2 were significantly suppressed in the hearts of mice treated with cetirizine.
These results suggest that cetirizine exerts its beneficial effects on viral myocarditis by suppressing expression of pro-inflammatory cytokines, genes related to cardiac remodeling in the hearts of mice.
我们曾表明,肥大细胞在压力超负荷和病毒性心肌炎诱导的小鼠心力衰竭进展中起着关键作用。在这项研究中,我们研究了选择性 H1 受体拮抗剂西替利嗪对脑炎心肌炎(EMC)病毒诱导的实验性病毒性心肌炎的影响。
4 周龄近交系雄性 DBA/2 小鼠经腹腔接种 10 噬菌斑形成单位(pfu)的 EMC 病毒。西替利嗪在病毒接种当天开始,以 1 或 10mg/kg/天的剂量口服给药,用于生存研究;以 1mg/kg 的剂量用于组织学和基因表达研究。
西替利嗪依赖剂量改善了生存率。用西替利嗪治疗的小鼠心脏重量与体重的比值显著降低。与对照组相比,用西替利嗪治疗的小鼠心脏中的心肌坏死面积明显较小。西替利嗪治疗的小鼠心脏中肿瘤坏死因子、白细胞介素 6 和金属蛋白酶 2 的基因表达明显受到抑制。
这些结果表明,西替利嗪通过抑制促炎细胞因子、与心脏重构相关的基因在小鼠心脏中的表达,对病毒性心肌炎发挥有益作用。