摘要
目的探讨阿托伐他汀对实验性自身免疫性心肌炎(experimental autoimmune myoeardi- tis,EAM)的作用及对心肌:MHCⅡ类分子表达的影响。方法以纯化猪心肌肌球蛋白免疫Lewis大鼠诱导EAM模型。随机分为阿托伐他汀治疗组和未治疗组。治疗组给予阿托伐他汀每天10 mg／kg,未治疗组给予等体积饮用水,分别以灌胃器给药,连续用药3周。以未免疫的同周龄Lewis大鼠为正常对照组。用药21 d后,检测超声心动图,脾T淋巴细胞增殖试验、HE染色观察心肌组织炎症浸润程度,免疫组化检测心肌内CD4^+或CD8^+T细胞的浸润及心肌组织MHCⅡ类分子的表达。RT-PCR检测心肌Ⅰ型、Ⅲ型及Ⅳ型MHCⅡ类分子转录活化因子(classⅡtransacfivator,cⅡTA)启动子转录。结果阿托伐他汀显著改善EAM大鼠心功能,治疗组心肌组织炎症浸润减轻,MHCⅡ类分子表达减少, 抗原诱导的T淋巴细胞增殖显著受抑制。Ⅳ型cⅡTA启动子表达下调,而Ⅰ、Ⅲ型cⅡTA启动子表达与未治疗组比较差异无统计学意义。结论阿托伐他汀显著改善EAM大鼠心功能及组织病理学表现,其机制可能通过下调Ⅳ型cⅡTA启动子转录,抑制心肌非专职性APC MHCⅡ类分子表达。表明他汀类对EAM具有免疫调节效应,从而在器官特异性自身免疫性心肌损伤的治疗中具有应用前景。
Objective To explore the immunoregulatory effects of atorvastatin, 3-hydroxy-3-methyl-glutaryl coenzyme A （HMC,-CoA） reduetase inhibitor, on the expression of MHCⅡ molecules in experimental autoimmune myocarditis （EAM）, and to explore the therapeutic potential for EAM. Methods Myocarditis was induced in lewis rats by the injection of porcine cardiac myosin. Atorvastatin （ 10 mg/kg each day） or vehicle was orally administered for 3 weeks. Twenty one days after immunization, echocardiography was examined and the severity of myocarditis was evaluated histopathologically. Immunohistochemistry techniques were used to distinguish the CD^4＋ or CD8^＋ ＋ T lymphocytes and to evaluate the expression of MHC Ⅱ molecules in the myocardium. Type Ⅰ , Ⅲ and Ⅳ C ⅡTA promoter transcription was compared by RT-PCR. Results Cardiac function was improved in the atorvastatin-treated group compared to the untreated one. In atorvastatin group, histological severity of myocarditis was attenuated, and the expression of MHCⅡ molecules in the ＂nonprofessional＂ APC in the myocardium was reduced. Transcription of typeⅣ CⅡTA promoter was down-regualated in the atorvastafin-treated group, but type Ⅰ , Ⅲ CⅡTA promoter mRNA were not statistically different. Conclusion Atorvastatin ameliorates cardiac function and inflammatory reaction of the myocardium in EAM, and so HMC,-CoA reductase blockade may be a promising new strategy for the treatment of organ specific autoimmune myocardial impairment.
出处
《中华微生物学和免疫学杂志》
CAS
CSCD
北大核心
2006年第4期293-297,共5页
Chinese Journal of Microbiology and Immunology
基金
哈尔滨医科大学研究生创新基金资助项目(2005)
