CYP3A4*1G和CYP3A5*3基因多态性对颌面外科手术患者舒芬太尼代谢的影响

武 婷 武莉 李乐 张丽娜 潘旭 王智

[摘要]目的：研究CYP3A4*1G和CYP3A5*3基因多態性相互作用对颌面外科手术患者舒芬太尼药物代谢的影响。方法：选取2018年10月-2019年12月在西安交通大学口腔医院颌面外科择期全麻下行颌面外科手术的88例患者为研究对象，年龄21～69岁，根据美国麻醉医师学会（ASA）分级为ASAⅠ或Ⅱ级。采用聚合酶链（PCR）-基因测序法对CYP3A4*1G和CYP3A5*3基因位点进行检测，根据两个基因的不同基因分型相互结合，分为Ⅰ、Ⅱ、Ⅲ+Ⅳ 三组。待患者进行麻醉诱导后，0.5h时抽取患者的外周静脉血液，采用高效液相色谱法（HPLC）检测患者体内舒芬太尼的血药浓度。术后24h时，对患者进行视觉模拟评分（VAS）评价疼痛程度，并记录患者24h内舒芬太尼的用量。结果：Ⅰ、Ⅱ、Ⅲ+Ⅳ 三组患者术中舒芬太尼血药浓度及术后24h VAS评分比较有统计学差异（P<0.05）。结论：CYP3A4*1G与CYP3A5*3共同影响舒芬太尼的体内代谢，两者基因多态性相结合，可作为术中指导舒芬太尼个体化用药的指标。

[关键词]CYP3A4酶;CYP3A5酶;基因多态性;舒芬太尼;药物代谢

[中图分类号]R73    [文献标志码]A    [文章编号]1008-6455（2021）07-0083-04

The Effect of Genetic Polymorphism Interaction between CYP3A4*1G and CYP3A5*3 for Maxillofacial Surgery with Metabolism of Sufentanil

WU Ting1，2，WU Li3，LI Le1，2，ZHANG Li-na1，2，PAN Xu1，2，WANG Zhi1，2

（1.Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research， Xi，an  710004，Shaanxi，China; 2.Department of Anesthesiology， Hospital of stomatology，Xi，an Jiaotong University，Xi，an 710004，Shaanxi，China;3.Department of Anesthesiology， Shanxi Provincial People's Hospital， Taiyuan 030012，Shanxi，China ）

Abstract： Objective This study aims to study the effect of genetic polymorphism interaction between CYP3A4*1G and CYP3A5*3 for Maxillofacial surgery with metabolism of sufentanil. Methods  A total of 88 patients who underwent Maxillofacial surgery under elective general anesthesia at the Department of maxillofacial surgery， Stomatological Hospital of Xi'an Jiaotong University from October 2018 to December 2019 were selected， aged 21-69， rated ASA Ⅰ or Ⅱ according to the American college of anesthesiologists （ASA）. To detect the locus of CYP3A4*1G and CYP3A5*3 with Polymerase chain （PCR） - gene sequencing， then divide them into three parts according dfferent genetic typings combining， respectively are Ⅰ，Ⅱand Ⅲ+Ⅳ. Draw patients peripheral venous blood half a hour after they were anesthesia induction， and detect the blood concentration of sufentanil with high performance liquid chromatography（HPLC）. Visual analogue scale （VAS） was used to evaluate the degree of pain at 24h after surgery， and the dosage of sufentanil was recorded within 24h. Results Ⅰ，Ⅱand Ⅲ+Ⅳ three parts patientstotal dosage of sufentanil and VAS scores exists statistic difference （P<0.05）. Conclusion CYP3A4*1G and CYP3A5*3 can have a genetic polymorphism interaction and affect metabolism of sufentanil together， therefore， it can be used as an intraoperative indicator to guide sufentanil individual medication.

Key words： CYP3A4;CYP3A5;gene polymorphism; sufentanil;drug metabolism

舒芬太尼作为阿片类镇痛药，被广泛应用于手术麻醉中。而目前临床上因为个体差异缺乏有效的指导用药指标，或因用药不足所造成的镇痛效果差，或用药过量引起的恶心、呕吐，甚至低血壓、呼吸抑制等不良反应时有发生[1-2]。CYP3A酶是人体药物代谢的关键酶，尤其是CYP3A4和CYP3A5存在基因多态性，其相互作用参与调节多种药物的体内代谢[3-4]。相关研究表明，CYP3A4基因多态性与舒芬太尼药物代谢有关[5-7]。CYP3A4*1G和CYP3A5*3等位基因分别是中国人群中CYP3A4和CYP3A5突变频率最常见的位点[8-11]。CYP3A4*1G和CYP3A5*3是否相互影响，共同参与调节舒芬太尼的体内代谢，目前尚无研究报道。……