Zhang S, Kodama M, Hanawa H, Izumi T, Shibata A, Masani F
First Department of Internal Medicine, Niigata University School of Medicine, Japan.
J Am Coll Cardiol. 1993 Apr;21(5):1254-60. doi: 10.1016/0735-1097(93)90254-x.
Preventive effects of cyclosporine, prednisolone and aspirin on autoimmune giant cell myocarditis in rats were investigated.
The therapeutic efficacy of immunosuppressants for human myocarditis is controversial. Although harmful effects of immunosuppressive therapy on experimental viral myocarditis have been reported, the effects on autoimmune myocarditis have not been investigated. Recently, a novel experimental autoimmune myocarditis model characterized by congestive heart failure and multinucleated giant cell has been established. Using this model, the preventive effects of cyclosporine, prednisolone and aspirin on autoimmune myocarditis were investigated.
Lewis rats were immunized with cardiac myosin in complete Freund's adjuvant on days 0 and 7. In experiment 1, four groups of seven rats each were established. Rats in each group received for 21 days intraperitoneal injections of either 1) phosphate-buffered saline solution, 1 ml/day (control); 2) cyclosporine, 20 mg/kg body weight per day (cyclosporine 20); 3) prednisolone, 4 mg/kg per day; or 4) aspirin, 15 mg/kg per day. In experiment 2, two additional groups (five rats each) received for 21 days an injection of cyclosporine, 1 or 5 mg/kg per day (cyclosporine 1 and cyclosporine 5, respectively). All rats were killed on day 21, when histopathologic studies were performed and the titers of antimyosin antibodies were measured.
The rats in the control, prednisolone and aspirin groups became ill and immobile in week 3. In comparison, rats in the cyclosporine 5 and 20 groups were still active until death was induced. Heart weight/body weight, lung weight/body weight and liver weight/body weight ratios in the rats in the cyclosporine 5 and cyclosporine 20 groups were significantly lower than those in the control group, and no differences were detectable among rats in the control, prednisolone and aspirin groups. The rats in the latter three groups and the cyclosporine 1 groups showed severe myocarditis with multinucleated giant cells. However, myocarditis was effectively prevented in the rats in the cyclosporine 5 and 20 groups. The histologic scores in each group were 2.91 in the control group, 2.14 in the prednisolone group, 2.91 in the aspirin group and 0.02, 2.58 and 0.07, respectively, in the cyclosporine 20, 1 and 5 groups. Production of antimyosin antibodies was remarkably suppressed in rats in the cyclosporine 5 and 20 groups in comparison with values in all other groups.
Autoimmune myocarditis is preventable by cyclosporine but not by prednisolone or aspirin in usual dosages.
研究环孢素、泼尼松龙和阿司匹林对大鼠自身免疫性巨细胞性心肌炎的预防作用。
免疫抑制剂对人类心肌炎的治疗效果存在争议。虽然已有报道免疫抑制疗法对实验性病毒性心肌炎有有害作用，但对自身免疫性心肌炎的影响尚未进行研究。最近，已建立了一种以充血性心力衰竭和多核巨细胞为特征的新型实验性自身免疫性心肌炎模型。利用该模型，研究了环孢素、泼尼松龙和阿司匹林对自身免疫性心肌炎的预防作用。
在第0天和第7天，用完全弗氏佐剂中的心肌肌球蛋白对Lewis大鼠进行免疫。在实验1中，建立了四组，每组7只大鼠。每组大鼠连续21天腹腔注射以下药物之一：1）磷酸盐缓冲盐水溶液，1毫升/天（对照组）；2）环孢素，20毫克/千克体重/天（环孢素20组）；3）泼尼松龙，4毫克/千克/天；或4）阿司匹林，15毫克/千克/天。在实验2中，另外两组（每组5只大鼠）连续21天注射环孢素，剂量分别为1或5毫克/千克体重/天（分别为环孢素1组和环孢素5组）。所有大鼠在第21天处死，进行组织病理学研究并测量抗肌球蛋白抗体滴度。
对照组、泼尼松龙组和阿司匹林组的大鼠在第3周时生病并活动减少。相比之下，环孢素5组和20组的大鼠直到被处死前仍很活跃。环孢素5组和20组大鼠的心脏重量/体重、肺重量/体重和肝脏重量/体重比值显著低于对照组，而对照组、泼尼松龙组和阿司匹林组大鼠之间无差异。后三组和环孢素1组的大鼠表现出伴有多核巨细胞的严重心肌炎。然而，环孢素5组和20组的大鼠有效地预防了心肌炎。每组的组织学评分分别为：对照组2.91，泼尼松龙组2.14，阿司匹林组2.91，环孢素20组、1组和5组分别为0.02、2.58和0.07。与所有其他组相比，环孢素5组和20组大鼠抗肌球蛋白抗体的产生明显受到抑制。
环孢素可预防自身免疫性心肌炎，而常规剂量的泼尼松龙或阿司匹林则不能。
