蛋白酶体抑制剂治疗实验性肌炎的研究

The therapeutic effect of proteasome inhibitor on autoimmune myositis in rats

目的:初步探讨蛋白酶体抑制剂MG-132在实验性肌炎动物模型中的疗效。方法:50只健康SD大鼠随机分为模型组40只,空白组10只,将模型组大鼠建立实验性肌炎模型。其中31只肌酶升高的大鼠分为糖皮质激素治疗组(11只,强的松5mg/只)、蛋白酶体抑制剂治疗组(11只,MG-1321mg/ml/只)和对照组(9只),治疗1个月后处死,比较3组的肌酶和肌肉组织病理改变。结果:模型组四肢骨骼肌呈多发性灶性炎症,大部分病变程度为2a级。治疗1个月后,激素组4只肌酶恢复正常,肌肉病理检查示病变轻,0级到1级病变占72.7%,肌细胞表达主要组织相容性复合物(MHC-I)分子量及CD8+T细胞浸润较对照组均显著减少(均P<0.05)。蛋白酶体抑制剂治疗组5只肌酶恢复正常,轻度病变占45.4%,MHC-I分子表达量及CD8+T细胞浸润与对照组间无统计学差异。结论:激素治疗炎性肌病的疗效肯定,蛋白酶体抑制剂的应用需进一步研究。

Objective：To observe the effects of proteasome inhibitors-MG132 and prednisone intervention on autoimmune myositis in rats.Methods：Fifty male SD rats were used in this study.They were randomly divided into 2 groups：model group（n=40）and control group（n=10）.The model group rats were established for experimental autoimmune myositis.Thirty one SD rats with evaluated creatine kinase （CK） were divided into three groups,a group of 11 rats received i.v.treatment with MG-132,1mg/ml once a week.The contrast group of 11 rats were treated with prednisone 5mg/d and a blank control group of 9 rats received no medicine.Rats were treated for one month and killed for serologic and histologic study.Results：There were multiple inflammatory lesions in the skeletal muscles in model group.Histological class was mainly 2a.After one month therapy,we found major histocompability complex（MHC-Ⅰ） molecules and CD8＋ T cells expression were significantly lower in prednisone group.Muscle pathological changes lessened in 8 rats,CK reduced to normal in 4 rats.Besides,pathological changes of muscle alleviated in 5 rats and CK reduced to normal in 5 rats in the proteasome inhibitor group.The expression of MHC-Ⅰ and CD8＋ T cells in proteasome group had no differences compare with control group.Conclusion：The application of proteasome inhibitors on autoimmune myositis needs further research.