碳酸酐酶Ⅲ改善实验性自身免疫性重症肌无力小鼠疲劳耐受性的研究

Experimental analysis of carbonic anhydrase Ⅲ on fatigue resistance of experimental autoimmune myasthenia gravis mice

目的:应用碳酸酐酶Ⅲ(CAⅢ)激动剂和抑制剂干预实验探讨CAⅢ对实验性自身免疫性重症肌无力(EAMG)小鼠肌无力症状和疲劳耐受性的影响。方法:应用纯化的加州电鳗乙酰胆碱受体(AChR)免疫C57BL小鼠制备EAMG动物模型,分别应用CAⅢ的抑制剂TFMS和激动剂Piperazine处理小鼠,观察小鼠的临床症状、肌肉重复电刺激的衰减,检测小鼠血清中细胞因子的变化,采用前臂抓握实验、ROTAROD转杆实验来鉴定小鼠运动耐力的变化。结果:本研究制备的EAMG模型具有典型的肌无力症状、肌肉重复电刺激衰减、AChR抗体增高以及血清中细胞因子(TNF-α,IL-1β,IL-6)增高的特征。应用CAⅢ激动剂的小鼠前爪抓力增强、肌肉重复电刺激衰减程度减轻、ROTAROD转杆实验坚持时间增长,给予CAⅢ的抑制剂处理的EAMG小鼠肌无力症状明显加重、前爪抓力减弱、肌肉重复电刺激衰减加重、转杆实验坚持时间缩短,与未干预组(P=0.04)和激动剂干预组(P<0.0001)相比差异具有统计学意义。结论:CAⅢ可以改善EAMG小鼠肌无力症状和电生理变化,对重症肌无力(MG)的病态易疲劳可能起保护作用。

Objective: To detect the effect of Carbonic anhydrase Ⅲ(CAⅢ) on the muscle weakness and fatigue resistance of experimental autoimmune myasthenia gravis mice(EAMG) using CAⅢ agonist or antiagonist. Methods: C57BL mice were immunized with AChR to make EAMG models.Mice were treated with CAⅢ agonist or antiagonist separately.The characterisitic of muscle weakness,paw grip test,muscle repetitive stimulations and ROTA ROD endurance test were observed in different groups. Results: The EAMG animal models we constructed had typical muscle fatigue,decrement on repetitive stimulations,increased AChR antibodies,and increased cytokines TNF-α,IL-1β,IL-6.Mice treated with CAⅢ agonist showed better paw grip endurance,muscle repetitive stimulations,ROTA ROD endurance,while those treated with CAⅢ antiagonist showed worsening of paw grip endurance,muscle repetitive stimulations,ROTA ROD endurance.There were significant differences between two treated groups ( P <0.000 1) and between treated and untreated groups( P =0.04). Conclusion: CAⅢ can improve the muscle weakness and repetitive stimulations,CAⅢ may help Myasthenia gravis on fatigue endurance.