ORM1基因多态性对罗库溴铵肌松时效的影响

Effect of ORM1 genetic polymorphism on time-course of muscle relaxation induced by rocuronium

目的评价ORM1基因多态性对罗库溴铵肌松时效的影响。方法择期全麻妇科腔镜手术患者70例，ASA分级Ⅰ或Ⅱ级，年龄25～55岁，体重指数20～25kg／m2。静脉注射咪达唑仑和芬太尼，靶控输注丙泊酚行麻醉诱导，待患者意识消失后行肌松定标，采用单刺激模式，静脉注射罗库溴铵0．6mg／kg，肌颤搐达最大抑制程度时行气管插管后机械通气，维持PET CO235～45mmHg。记录罗库溴铵起效时间、无反应期、临床作用时间、75％恢复时间和恢复指数。术前采集外周静脉血标本，采用ELISA法测定血浆α1-酸性糖蛋白和C-反应蛋白的浓度，生化法测定白蛋白浓度，应用PCR—RFLP法行ORM1基因分型，根据基因型分为3组：野生纯合子组（AA组）基因型为ORM1＊E1/＊F1、突变杂合子组（AG组）基因型为ORM1＊F1／＊S和突变纯合子组（GG组）基因型为ORM1＊S／＊S。结果AA组40例，AG组25例和GG组5例。3组血浆α1-酸性糖蛋白、白蛋白和C-反应蛋白的浓度差异无统计学意义（P〉0．05）。与AA组比较，AG组和GG组罗库溴铵临床作用时间、75％恢复时间和恢复指数延长（P〈0．05），起效时间和无反应期差异无统计学意义（P〉0．05）。结论ORM1基因多态性是影响罗库溴铵时效个体差异的遗传因素之一。

Objective To evaluate the effect of ORM1 genetic polymorphism on the time-course of muscle relaxation induced by rocuronium. Methods Seventy American Society of Anesthesiologists physi- cal status Ⅰ or Ⅱ patients, aged 25-55 yr, scheduled for elective gynecological laparoscopic surgery, with body mass index of 20-25 kg/m2 , were enrolled in this study. Anesthesia was induced with iv midazolam and fentanyl and target-controlled infusion of propofol. After the patients lost consciousness, neuromuscular block was assessed with TOF Wateh-SX using single stimulation of the ulnar nerve. When the maximal twitch depression was achieved, tracheal intubation was facilitated with roeuronium 0.6 mg/kg. The patients were mechanically ventilated. End-tidal carbon dioxide partial pressure was maintained at 35-45 mmHg. The onset time, nonresponse time, clinical duration, 75% recovery time and recovery index of roeuronium were recorded. Peripheral venous blood samples were collected before surgery for determination of concen- trations of plasma alphal acid glycoprotein, C-reactive protein （by enzyme-linked immunosorbent assay） and albumin （by biochemical method）. ORM1 genotypes were detected by polymerase chain reaction-re- striction fragment length polymorphism. The patients were divided into 3 groups according to the ORM1 gen-otypes： wild homozygote （ ORM1＊F1/＊F1 ） group （ AA group）, mutation heterozygote （ORM1＊F1/＊S） group （AG group） and mutation homozygote （ORM1＊S/＊S） group （GG group）. Results There were 40 cases in group AA, 25 cases in group AG, and 5 cases in group GG. There were no significant differences in plasma alphal acid glycoprotein, albumin and C-reactive protein concentrations between the three groups （P〉0.05）. Compared with group AA, the clinical duration, 75% recovery time and recovery index of rocuronium were significantly prolonged （P〈0.05）, and no significant change was found in the onset time and nonresponse time in AG and GG groups （P〉0.05）. Conclusion ORM1 genetic polymorphism is one of the genetic factors which affect the time-course of muscle relaxation induced by rocuronium.