实验性自身免疫性重症肌无力模型大鼠腓肠肌低密度脂蛋白受体相关蛋白4表达的特点

摘要

目的 探讨实验性自身免疫性重症肌无力(EAMG)模型大鼠腓肠肌低密度脂蛋白受体相关蛋白4(LRP4)表达的特点.方法 将30只大鼠随机分为EAMG组、对照组和空白组.以小鼠乙酰胆碱受体(AChR)基因为模板合成AChR抗原,以Lewis大鼠为免疫动物.EAMG组采取主动免疫法将AChR抗原与弗氏佐剂混合制成乳剂,注射入大鼠背部皮下.对照组在相同部位注射等量的弗氏佐剂.空白组在相同部位注射等量的生理盐水.8周后使用低频重复电刺激(RNS)检测肌电RNS衰减率.采用蛋白免疫印迹法检测腓肠肌LRP4含量.结果 EAMG组所有大鼠在8周后出现肌无力症状,对照组、空白组大鼠无肌无力症状.EAMG组大鼠RNS衰减率明显高于对照组和空白组(均P<0.05).EAMG组大鼠腓肠肌LRP4蛋白的相对含量明显低于对照组和空白组(均P<0.05).结论 EAMG大鼠中,当AChR被自身抗体破坏时,可能导致包含LRP4在内的整条信号通路受损,进而使LRP4含量减少.LRP4是神经肌肉接头信号通路完整的重要分子.%Objective To observe the express characteristics of low density lipoprotein receptor related protein 4 (LRP4) in gastrocnemius muscle in experimental autoimmune myasthenia gravis (EAMG) rats model.Methods Thirty rats were randomly divided into EAMG group,control group and blank group.Acetylcholine receptors (AChR) gene in mice was the template synthesis of AChR antigen,and Lewis rats were the immuned animal.The rats of EAMG group were immunized with the AChR antigen and complete Freund's adjuvant.Control group were immunized with the complete Freund's adjuvant.The rats of blank group were immunized with the physiological saline.The decrement percentage of repetitive never stimulation (RNS) of each group muscle after 8 weeks was detected.The content of LRP4 in gastrocnemius muscle cells was detected by Western Blot.Results The rats of EAMG group were found symptoms of muscle weakness after 8 weeks,but the control group and blank group were not found symptoms of muscle weakness in rats.The attenuation rate of RNS in EAMG group was significantly higher than those in the control group and blank group (all P<0.05).The expression of LRP4 in EAMG group was significantly lower than those in the control group and blank group (all P<0.05).Conclusions In EAMG rats,when the AChR destroyed by autoantibodies,the whole article signaling pathways is damaged,and the expression of LRP4 is decreased.LRP4 is a neuromuscular joint complete important molecules.