CHRNA1基因多态性对罗库溴铵肌松效应的影响

目的 探讨CHRNA1基因多态性对罗库溴铵肌松效应的影响.方法 择期全麻下行腹部手术患者95例,ASA分级Ⅰ或Ⅱ级,性别不限,年龄18～64岁,体重指数18～25 kg/m2,腋温36～37℃.患者来自河北省或周边地区,且均为汉族,彼此无血缘关系.术前采集外周静脉血样5 ml,EDTA抗凝,蛋白酶K消化,饱和氯化钠盐析法提取DNA.采用聚合酶链反应-限制性片段长度多态性技术和序列分析法对CHRNA1上游478 bp处AG多态性位点rs16862847进行检测,根据基因型将患者分为野生型纯合子组(AA组,n=71)、突变型杂合子组(AG组,n=19)和突变型纯合子组(GG组,n=5).人室后静脉注射芬太尼4μg/kg和异丙酚2 mg/kg,意识消失后启动TOF-Watch SX型加速度肌松监测仪单刺激模式监测拇内收肌颤搐程度,随后静脉注射罗库溴铵0.2 mg/kg,观察肌松效应.结果 与AA组相比,AG组和GG组肌松起效时肌颤搐程度降低(P＜0.05).AG组和GG组肌松起效时肌颤搐程度比较差异无统计学意义(P＞0.05).结论 CHRNA1基因多态性可影响患者罗库溴铵的肌松效应,提示遗传因素是导致肌松药药效个体差异的原因之一.

Effect of CHRNA1 genetic polymorphism on neuromuscular blockade induced with rocuronium

Objective To investigate the effect of CHRNA1 genetic polymorphism on neuromuscular blockade induced with rocuronium. Methods Ninety-five ASA Ⅰ or Ⅱ patients of both sexes (age 18-64 yr,BMI 18-25 kg/m2 ) undergoing elective intra-abdominal surgery under general anesthesia were divided into 3 groups according to their genotypes: group Ⅰ AA ( n = 71 ); group Ⅱ AG ( n = 19) and group Ⅲ GG ( n = 5). ECG,BP, HR and SpO2 were continuously monitored during anesthesia. Neuromuscular function was assessed by response of adductor pollicis muscle to stimulation of the ulnar nerve using TOF-Watch SX monitor. Genomic DNA was extracted by using proteinase K digestion followed by a salting out prosedure. rs16862847 polymorphisms were analyzed by PCR-restriction fragment length polymorphism analysis and direct sequence analysis. Anesthesia was induced with fentanyl 4 μg/kg and propofol 2 mg/kg. Rocuronium 0.2 mg/kg was injected iv as soon as the patients lost consciousness. Results The twitch height of adductor pollicis muscle was significantly decreased in group AG and GG as compared with group AA ( P ＜ 0.05). There was no significant difference between group AG and GG.Conclusion CHRNA1 genetic polymorphism can influence the neuromuscular blockade induced with rocuronium,indicating that the genetic factor is one of the reasons contributing to the individual variation in neuromuscular blockade induced with muscle relaxants in patients.