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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
【摘要】 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。
【Abstract】 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.
- 【文献出处】 中日友好医院学报 ,Journal of China-Japan Friendship Hospital , 编辑部邮箱 ,2008年01期
- 【分类号】R593.26
- 【下载频次】86