ERK信号通路在烧伤大鼠骨骼肌对非去极化肌松药抵抗形成时γ-AChR上调中的作用

Role of ERK signaling pathway in up-regulation of γ-AChR during development of resistance to non-depolarizing muscular relaxants in skeletal muscles of burned rats

目的 评价细胞外信号调节激酶（ERK）信号通路在烧伤大鼠骨骼肌对非去极化肌松药抵抗形成时胎儿型乙酰胆碱受体（γ-AChR）上调中的作用.方法 SPF级成年雄性SD大鼠30只,体重230～ 250 g,9～10周龄,采用随机数字表法分为3组（n=10）：对照组（C组）、烧伤组（B组）和ERK1/2抑制剂U0126组（U组）.采用热固体烫伤法制备大鼠烧伤模型,烧伤后1.5 h时U组腹腔注射U0126 15 mg/kg,C组和B组注射等容量DMSO.于模型制备后第7天取胫骨前肌,采用RT-PCR法检测μ-AChR和成人型乙酰胆碱受体（ε-AChR）的mRNA表达水平,采用肌张力实验绘制罗库溴铵的浓度-效应曲线并计算半数有效抑制浓度（IC50）及其95％可信区间.结果 与C组比较,B组骨骼肌细胞μ-AChR mRNA表达上调,IC50增加（P＜0.05）;与B组比较,U组骨骼肌细胞y-AChRmRNA表达下调,IC50减小（P＜0.05）.3组骨骼肌细胞ε-AChR mRNA表达差异无统计学意义（P＞0.05）.结论 烧伤大鼠骨骼肌对非去极化肌松药抵抗形成时γ-AChR上调依赖于ERK信号通路的激活.

Objective To evaluate the role of ERK signaling pathway in up-regulation of fetal gamma-acetylcholine receptor （μ-AChR） during the development of resistance to non-depolarizing muscular relaxants in skeletal muscles of burned rats.Methods Thirty adult male SPF Sprague-Dawley rats,weighing 230-250 g,aged 9-10 weeks,were randomly divided into 3 groups （n=10 each） using a random number table：control group （C group）,burn group （B group） and ERK1/2 inhibitor U0126 group （U group）.The surface area of bilateral hindlimbs was shaved,and the tibialis anterior muscle of the right hiudlimb was exposed to 95 ℃ copper for 12 s in anesthetized rats.At 1.5 h after burn,15 mg/kg U0126 was injected intraperitoneally in group U,and the equal volume of dimethyl sulfoxide was given in C and B groups.The tibialis anterior muscle was obtained on 7th day after establishment of the model for determination of the expression of μ-AChR and adult epsilon-AChR （ε-AChR） mRNA in skeletal muscle cells using real-time polymerase chain reaction.The concentration-effect curve of rocuronium was drawn using muscular tension experiment,and the half inhibitory concentration （IC50） and 95% confidence interval were calculated.Resuits Compared with group C,the expression of μ-AChR mRNA in skeletal muscle cells was significantly up-regulated,and the IC50 was significantly increased in group B （P〈0.05）.Compared with group B,the expression of γ-AChR mRNA in skeletal muscle cells was significantly down-regulated,and the IC50 was significantly decreased in group U （P〈0.05）.There was no significant difference in the expression of ε-AChR in skeletal muscle cells between the three groups （P〉0.05）.Conclusion Up-regulation of μ,-AChR is dependent on activation of ERK signaling pathway during the development of resistance to non-depolarizing muscular relaxants in skeletal muscles of burned rats.