阿托伐他汀对Lewis大鼠实验性自身免疫性心肌炎作用的研究  

Effects of atorvastatin on the experimental autoimmune myocarditis in Lewis rats

作　　者：曹滨冬[1] 李为民[2] 高成[3] 沈景霞[2] 孔一慧[2] 韩薇[2] 甘润韬[2] 耿建强[2] 李悦[2] 杨树森[2] 

机构地区：[1]哈尔滨医科大学附属第四医院VIP病房 [2]哈尔滨医科大学心内科,黑龙江哈尔滨150001 [3]哈尔滨医科大学神经外科,黑龙江哈尔滨150001

出　　处：《中国病理生理杂志》2007年第3期536-539,共4页Chinese Journal of Pathophysiology

基　　金：哈尔滨医科大学研究生创新基金资助项目(2005)

摘　　要：目的:探讨阿托伐他汀对实验性自身免疫性心肌炎(EAM)大鼠Th1/Th2偏离的影响及对EAM的治疗价值。方法:6-8周雄性Lewis大鼠31只,其中8只作为正常对照;23只以猪心肌肌球蛋白免疫制成EAM模型,免疫后随机分为阿托伐他汀大剂量(10mg.kg-1.d-1)组、小剂量(1mg.kg-1.d-1)组和未治疗组,连续用药21d。第21d,行超声心动图检测;取心肌组织,观察大体及镜下炎症程度;ELISA检测血浆IL-2、IL-4、IL-10及IFN-γ等细胞因子水平,并以IFN-γ/IL-4比值作为Th1/Th2偏离方向指标。结果:阿托伐他汀使EAM大鼠心室肥厚减轻,LVEDd降低,射血分数增加;心脏重量/体重比值及炎症程度分级显著降低;Th1型细胞因子(IFN-γ,IL-2)水平降低,Th2型细胞因子水平(IL-4,IL-10)升高。3组间TC、TG及HDL-C水平未见明显差异。结论:阿托伐他汀使Th1/Th2平衡向Th1方向偏离,抑制EAM炎症反应。表明阿托伐他汀的免疫调节效应及在自身免疫病治疗中的应用前景。AIM： To test the hypothesis that atorvastatin affects T cell - mediated autoimmunity through modulating the balance of Th1/Th2 and reduces the severity of EAM. METHODS： Myocarditis was induced in Lewis rats by injection of porcine cardiac myosin. High - dose （ 10 mg· kg^- 1· d ^- 1 ） or low - dose （ 1 mg· kg^-1· d^ -1 ） atorvastatin or vehicle was administered orally for 3 weeks. On day 21, echocardiography was examined and the severity of myocarditis was detected by histopathological evaluation. Levels of serum IFN -γ, IL -2, IL -4 and IL - 10 were measured by ELISA. RESULTS： Cardiac function and histological severity of myocarditis were improved in the two atorvastatin - treated groups. Treatment with atorvastatin decreased the levels of Th 1 cytokine （ IFN - γ, IL - 2） and increased the levels of Th2 cytokine （ IL - 4, IL - 10）. CONCLUSION： These results suggest that HMG - CoA reductase blockade may be a promising new strategy for the treatment of autoimmune myocarditis.

关 键 词：阿托伐他汀 T淋巴细胞 辅助诱导 心肌炎 

分 类 号：R542[医药卫生—心血管疾病]