CYP3A4*1G基因多态性对胃肠外科老年患者舒芬太尼全麻诱导中应激反应的影响
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摘要
目的:研究胃肠外科手术老年患者CYP3A4*1G基因多态性与舒芬太尼对应激反应抑制作用的相关性。方法:择期全麻胃肠外科手术老年患者119例,以焦磷酸测序法检测CYP3A4*1G基因多态性,根据基因型进行分组,比较不同基因型患者插管前后及切皮前后应激反应(收缩压、舒张压和心率)的变化。麻醉诱导方法为依次给予咪达唑仑、舒芬太尼、维库溴铵、依托咪酯。结果:CYP3A4*1G等位基因突变率为20.17%,符合Hardy-Weinberg平衡。将患者分为野生型组、突变型杂合子组和突变型纯合子组,三组患者插管前后的收缩压、舒张压和心率的波动及切皮前后的舒张压的波动的差别无统计学意义(P>0.05),而野生型组与突变型杂合子组患者切皮前后的收缩压和心率的波动的差别有统计学意义(P<0.05)。结论:CYP3A4*1G基因多态性与舒芬太尼抑制切皮引起的应激反应的强弱有关。
OBJECTIVE To study relationship between CYP3A4*1Ggenetic polymorphism and stress reaction during induction of general anesthesia with sufentanil in elderly patients receiving gastrointestinal surgery.METHODS A total of 119 elderly patients received elective gastrointestinal surgery under general anesthesia were recruited into this study.CYP3A4*1G genetic polymorphism was analyzed in pyrosequencing method,and patients were grouped according to their genotypes.Stress reaction parameters,including systolic blood pressure,diastolic blood pressure and heart rate,were recorded prior to anesthesia induction(T0),before and instantly after intubation(T1and T2)and skin cut(T3and T4),and were analyzed by different genotypes.During anesthesia induction,midazolam,sufentanil,vecuronium bromide and etomidate were given in orders.RESULTS CYP3A4*1Gallele rate was 20.17%,in accordant with Hardy-Weinberg equilibrium.Patients were divided into 3groups,wild-type group,mutant-heterozygous group and mutant-homozygous group.No significant difference was noted between each two groups(P>0.05)in fluctuations of systolic blood pressure,diastolic blood pressure,heart rate before and instantly after intubation(T2-T1)and in fluctuations of diastolic blood pressure before and instantly after skin cut(T4-T3).Meanwhile,between wild-type and mutant-heterozygote group,a significant difference appeared in fluctuations of systolic blood pressure and heart rate before and instantly after skin cut(P<0.05).CONCLUSION CYP3A4*1Ggenetic polymorphism is associated with strength of stress reaction of skin cutting inhibited by sufentanil.
OBJECTIVE To study relationship between CYP3A4*1Ggenetic polymorphism and stress reaction during induction of general anesthesia with sufentanil in elderly patients receiving gastrointestinal surgery.METHODS A total of 119 elderly patients received elective gastrointestinal surgery under general anesthesia were recruited into this study.CYP3A4*1G genetic polymorphism was analyzed in pyrosequencing method,and patients were grouped according to their genotypes.Stress reaction parameters,including systolic blood pressure,diastolic blood pressure and heart rate,were recorded prior to anesthesia induction(T0),before and instantly after intubation(T1and T2)and skin cut(T3and T4),and were analyzed by different genotypes.During anesthesia induction,midazolam,sufentanil,vecuronium bromide and etomidate were given in orders.RESULTS CYP3A4*1Gallele rate was 20.17%,in accordant with Hardy-Weinberg equilibrium.Patients were divided into 3groups,wild-type group,mutant-heterozygous group and mutant-homozygous group.No significant difference was noted between each two groups(P>0.05)in fluctuations of systolic blood pressure,diastolic blood pressure,heart rate before and instantly after intubation(T2-T1)and in fluctuations of diastolic blood pressure before and instantly after skin cut(T4-T3).Meanwhile,between wild-type and mutant-heterozygote group,a significant difference appeared in fluctuations of systolic blood pressure and heart rate before and instantly after skin cut(P<0.05).CONCLUSION CYP3A4*1Ggenetic polymorphism is associated with strength of stress reaction of skin cutting inhibited by sufentanil.
引文
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[12]王寿世,宋婷婷,宁吉顺,等.舒芬太尼用于老年胸科病人全身麻醉诱导的血液动力学变化[J].中国临床研究,2011,24(11):984-986.
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[14]李丹滢,方芸.CYP3A4/5,ABCBl基因单倍型与中国肾移植患者他克莫司血药谷浓度相关性的研究[J].药学研究,2014,22(1):20-24.
[15]Edwards ND,Alford AM,Dobson PM,et al.Myocardial ischemia during tracheal intubation and extubation[J].Br J Anaesth,1994,73(4):537-539.
[16]Tan PC,Hassan SK,Mohamad NA,et al.Cytochrome P4503A4 genetic polymorphisms and post-operative fentanyl requirements[J].J Clin Pharm Ther,2012,37(1):100-104.
[17]Kim KM,Kim HS,Lim SH,et al.Effects of genetic polymorphisms of OPRM1,ABCB1,CYP3A4/5 on postoperative fentanyl consumption in Korean gynecologic patients[J].Int J Clin Pharmacol Ther,2013,51(5):383-392.
[2]Yuan R,Zhang X,Deng Q,et al.Impact of CYP3A4*1G polymorphism on metabolism of fentanyl in Chinese patients undergoing lower abdominal surgery[J].Clin Chim Acta,2011,412(9/10):755-760.
[3]Liao Q,Chen DJ,Zhang F,et al.Effect of CYP3A4*18B polymorphisms and interactions with OPRM1 A118G on postoperative fentanyl requirements in patients undergoing radical gastrectomy[J].Mol Med Rep,2013,7(3):901-908.
[4]贺宝霞,赵秀莉,石磊,等.CYP3A4*1G基因多态性及功能的初步探讨[J].河南医学研究,2014,23(7):4-7.
[5]Fukushima-Uesaka H,Saito Y,Watanabe H,et al.Haplotypes of CYP3A4 and their close linkage with CYP3A5 haplotypes in a Japanese population[J].Hum Mutat,2004,23(1):100.
[6]Tateishi T,Krivoruk Y,Ueng YF,et al.Identification of human liver cytochrome P-450 3A4 as the enzyme responsible for fentanyl and sufentanil N-dealkylation[J].Anesth Analg,1996,82(1):167-172.
[7]Guitton J,Buronfosse T,Désage M,et al.Possible involvement of multiple cytochrome P450S in fentanyl and sufentanil metabolism as opposed to alfentanil[J].Biochem Pharmacol,1997,53(11):1613-1619.
[8]Eriksen J,Berthelsen P,Ahn NC,et al.Early response in central hemodynamics to high doses of sufentanil or morphine in dogs[J].Acta Anaesthesiol Scand,1981,25(1):33-38.
[9]朱志华,赵国庆,孙海.舒芬太尼对老年患者全麻诱导应激反应的影响[J].临床麻醉学杂志,2009,25(1):16-17.
[10]张红芹,潘丙德,张济文,等.舒芬太尼对脑外科麻醉诱导时血流动力学影响[J].实用医技杂志,2008,15(8):1060-1062.
[11]李岳振,王文军,洪立群.舒芬太尼老年人麻醉诱导抑制心血管反应的药效学研究[J].海南医学,2014,25(4):501-503.
[12]王寿世,宋婷婷,宁吉顺,等.舒芬太尼用于老年胸科病人全身麻醉诱导的血液动力学变化[J].中国临床研究,2011,24(11):984-986.
[13]舒芬太尼多中心研讨小组.舒芬太尼多中心研讨会纪要[J].临床麻醉学杂志,2004,20(11):668.
[14]李丹滢,方芸.CYP3A4/5,ABCBl基因单倍型与中国肾移植患者他克莫司血药谷浓度相关性的研究[J].药学研究,2014,22(1):20-24.
[15]Edwards ND,Alford AM,Dobson PM,et al.Myocardial ischemia during tracheal intubation and extubation[J].Br J Anaesth,1994,73(4):537-539.
[16]Tan PC,Hassan SK,Mohamad NA,et al.Cytochrome P4503A4 genetic polymorphisms and post-operative fentanyl requirements[J].J Clin Pharm Ther,2012,37(1):100-104.
[17]Kim KM,Kim HS,Lim SH,et al.Effects of genetic polymorphisms of OPRM1,ABCB1,CYP3A4/5 on postoperative fentanyl consumption in Korean gynecologic patients[J].Int J Clin Pharmacol Ther,2013,51(5):383-392.