摘要
目的观察α2A肾上腺素能受体(ADRA2A)基因多态性对右美托咪定镇静效果的影响,初步探讨右美托咪定镇静效果个体差异的遗传学机制。方法选择硬膜外麻醉下行下肢手术的患者105例,ASAⅠ~Ⅱ级。术前采集患者外周静脉血,采用PCR-RFLP法进行ADRA2A启动子区域C1291G(rs1800544)基因分型。选择L 2/L 3间隙行硬膜外穿刺置管,控制麻醉平面在T 10以下;麻醉完成后开始泵注右美托咪定,负荷剂量1μg/kg,10 min恒速泵注,维持剂量0.5μg/(kg·h),1 h后停止泵注。从用药开始至1 h,每隔5 min记录患者脑电双频指数(BIS)、改良的警觉/镇静评分(OAA/S)、BP、HR、SpO 2、RR,并记录术中低血压、心动过缓、呼吸抑制等不良事件。结果105例患者中,ADRA2A基因rs1800544位点等位基因CC型16例、CG型52例、GG型37例,三种等位基因型患者年龄、BMI、ASA分级差异无统计学意义。自用药5 min开始,所有患者BIS开始下降;用药15~40 min,CG、GG型患者BIS高于CC型(P均<0.05)。自用药30 min开始,所有患者改良的OAA/S开始升高;用药35~50 min,CG、GG型患者改良的OAA/S低于CC型。CG、GG型患者在各时间点BIS、改良的OAA/S差异无统计学意义,不同等位基因患者BP、HR及不良事件发生率差异无统计学意义。结论与ADRA2A基因rs1800544位点CC型等位基因患者相比,CG、GG型等位基因患者对右美托咪定的镇静反应迟缓,不易进入睡眠状态。
Objective To investigate the effect ofα2A-adrenergic receptor(ADRA2A)gene polymorphism on the sedative effect of dexmedetomidine,and to preliminarily explore the genetic mechanism of individual differences in the sedative effect of dexmedetomidine.Methods One hundred and five patients with American Society of Anesthesiologists(ASA)physical statusⅠandⅡ,undergoing lower extremity surgery under epidural anesthesia were selected.Venous blood was drawn before the operation,the genotypes of ADRA2A C1291G(rs1800544)in the promoter region of the candidate gene were done by PCR-RFLP.We selected the L 2/L 3 gap for epidural catheterization and controlled the anesthesia plane below T 10.Dexmedetomidine infusion was initiated after epidural catheterization,a loading dose of 1μg/kg dexmedetomidine was pumped intravenously with a constant speed for 10 min,the pumping was stopped after a maintenance rate of 0.5μg/(kg·h)for 1 hour.From the beginning of infusion until 1 hour later,EEG bispectral index(BIS),modified Observer's Assessment of Alertness/Sedation scale(OAA/S scale),BP,HR,SpO 2 and RR were recorded every 5 minutes,and intraoperative hypotension,bradycardia,respiratory depression and other adverse events were also recorded.Results Among 105 patients,there were 16 cases of type CC for ADRA2A gene rs1800544 allele,52 cases of CG type and 37 cases of GG type.There was no significant difference in age,BMI or ASA status between the patients with three allele types.The BIS values of all patients began to decrease after 5 minutes of the infusion of dexmedetomidine;after 15-40 minutes,the values of BIS in patients with CG and GG were higher than those in patients with CC(all P<0.05).The modified OAA/S score of all patients began to increase after 30 minutes of the infusion of dexmedetomidine,in 35 to 50 minutes,the modified OAA/S scores in patients with CG and GG were lower than those in patients with CC(P<0.05).There was no significant difference in BIS or modified OAA/S between the CG and GG patients at different time points.There was no significant difference in the incidence of BP,HR,and adverse events among patients with different alleles.Conclusion Compared with individuals with ADRA2A gene rs1800544 allele CC genotype,patients with CG and GG genotypes have a slow sedative response to dexmedetomomidine and are not easy to fall asleep.
作者
刘刚刚
李涛
孙巧霞
姜美如
马加海
LIU Ganggang;LI Tao;SUN Qiaoxia;JIANG Meiru;MA Jiahai(The Affiliated Yantai Yuhuangding Hospital of Qingdao University,Yantai 264000,China)
出处
《山东医药》
CAS
2019年第26期31-34,共4页
Shandong Medical Journal
基金
山东省烟台市重点研发项目(2019YD022)
