大蒜新素治疗小鼠巨细胞病毒性心肌炎作用研究

Allitridin treatment of cytomegalovirus-induced myocarditis in mice and its role in anti-cytomegalovirus mechanisms

目的探讨大蒜新素对小鼠巨细胞病毒(MCMV)性心肌炎治疗作用及其抗CMV机制。方法60只BALB/c小鼠随机分成大蒜新素治疗组(20只)、安慰剂组(20只)和正常对照组(20只)。大蒜新素治疗组接种MCMVK181后24h开始用大蒜新素一般剂量(25mg/kg)腹腔注射,每天1次,共14d;安慰剂组和正常对照组仅用等量生理盐水。各组分别于治疗后第3、5、7、14天各处死5只小鼠,观察小鼠心肌组织病理损害;用双抗体夹心ELISA法检测小鼠心肌组织细胞因子IFNγ表达水平;用RTPCR方法检测小鼠脾核转录因子TbetmRNA表达强度。结果MCMV感染下调小鼠TbetmRNA和TH1类细胞因子IFNγ的表达(P<0.01);大蒜新素能诱导MCMV性心肌炎模型小鼠转录因子TbetmRNA和细胞因子IFNγ的表达显著增加(P<0.01),并显著改善MCMV感染小鼠心肌组织病理损害(P<0.05)。结论大蒜新素通过上调转录因子TbetmRNA表达进而促进TH1类细胞因子IFNγ分泌,诱导和促进TH1优势应答反应,增强机体特异性细胞免疫功能而发挥抗MCMV作用。

Objective To investigate the effects of allitridin on cytomegalovirus-induced myocarditis in mice and to analyze its role in anti-cytomegalovirus mechanisms. Methods Sixty mice were randomly divided into allitridin therapy group, infected group and control group. Allitridin therapy group were given to mice via the intraperitoneal (i.p.) route once a day with general dosage (25 mg/kg) 24 hours after MCMV infection; placebo group was given with the same volume of 0.89% sodium chloride and control group was only given with the same volume of 0.89% sodium chloride without MCMV infection. All experimental mice were sacrificed at 3, 5, 7, 14 days after treatment (n=5 per time point). Myocarditis was diagnosed at heart sections as the average number of foci of cellular infiltration. The expression levels of transcription factor T-bet mRNA were measured by RT-PCR. The expression levels of T_H1 cytokine IFN-γ were measured by ELISA. Results MCMV infection markedly down-modulated the expression of IFN-γ and T-bet mRNA (P<0.01). Allitridin significantly up-regulated the expression of T_H1 cytokines IFN-γ and T_H1-specific transcription factor T-bet mRNA (P<0.01). A significant reduction in myocarditis morbility was observed with allitridin treatment (P<0.05). Conclusion Allitridin may promote IFN-γ secretion through up-regulating the expression of T_H1-specific transcription factor T-bet mRNA, indicating a T_H1 dominant state which enhances the specific cellular immune reactions against cytomegalovirus (CMV) and is helpful for clearance of CMV in host.