OATP1B1，MDR1，和CHRNA1基因多态对罗库溴铵肌松效应的影响

发布时间：2018-05-07 15:42

本文选题：遗传药理学 + 基因多态性　；参考：《中南大学》2014年硕士论文

【摘要】：目的：观察OATP1B1, MDR1和CHRNA1基因多态对全麻病人围术期肌松药罗库溴铵肌松效应的影响。方法：全麻下行择期耳鼻喉科手术患者207例,ASA I或Ⅱ级,18-59岁。麻醉诱导方案：依次静注咪唑达仑0.06mg/kg,舒芬太尼0.7u g/kg,丙泊酚1mg/kg,罗库溴铵0.6mg/kg;麻醉维持方案：靶控输注丙泊酚(血浆靶浓度3-5μg/ml,)和瑞芬太尼(效应室靶浓度3～6ng/ml)。整个过程用TOF-Watch SX型加速度肌松监测仪监测肌松效应,肌松恢复到25%时追加罗库溴铵0.15mg/kg。记录从诱导开始到麻醉结束患者生命体征的变化。记录罗库溴铵的起效时间、肌松恢复到25%时间、恢复到90%时间。抽取受试者的静脉血2m1,采用聚合酶链反应一限制性片段长度多态性(PCR-RFLP)的方法对患者OATP1B1, MDR1和CHRNA1进行基因型分析。计量资料应用X±SD表示；不同基因型之间参数的比较采用单因素方差分析和卡方检验,影响罗库溴铵作用时效的独立因素分析采用单因素回归分析；不同影响因素与罗库溴铵作用时效的分析采用多因素回归分析。结果：①OATPIBI388A/G不同基因型占总人数的比例分别是AA组10%,AG组37%,GG组53%；OATP1B1521T/C不同基因型占总人数的比例分别是TT组80%,TC组18%,CC组2%;MDR11236C/T不同基因型占总人数的比例分别是CC组13%,CT组49.5%,TT组37.5%；MDR13435C/T不同基因型占总人数的比例分别是CC组41.5%,CT组39%,TT组19.5%；CHRNA1rs168628A/G不同基因型占总人数的比例分别是AA组91%,AG组8%,GG组2%。②OATP1B1388A/G不同基因型的患者,相对于AA组而言,AG组和GG组肌松诱导剂量和追加剂量的维持时间以及肌松恢复时间均更长(P0.05)；MDR11236C/T位点不同基因型的患者,TT组肌松诱导剂量和追加剂量的维持时间均比CC和CT更长(P0.05),TT组肌松恢复时间比CC和CT组也更长(P0.05)；OATP1B1521T/C, MDR13435C/T, CHRNA1rs168628A/G不同基因型的患者,肌松效应没有显著差异(P0.05)。结论：OATP1B1521T/C, MDR13435C/T, CHRNA1rs168628A/G基因多态性多罗库溴铵的临床作用时间的影响有限,而OATP1B1388AG和MDR11236CT基因多态性可影响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。
[Abstract]:Aim: to investigate the effects of OATP 1B 1, MDR1 and CHRNA1 gene polymorphisms on muscle relaxant rocuronium bromide in patients undergoing general anesthesia. Methods: 207 patients undergoing selective otolaryngologic surgery under general anesthesia were enrolled in ASA I or II grade 18-59 years old. Anesthesia induction scheme: intravenous injection of midazolam 0.06 mg / kg, sufentanil 0.7 u g / kg, propofol 1 mg / kg, rocuronium 0.6 mg / kg; anesthesia maintenance scheme: target controlled infusion of propofol (plasma target concentration 3-5 渭 g / ml) and remifentanil (target concentration 3 ~ 6 ng / ml 路ml ~ (-1). During the whole process, TOF-Watch SX acceleration muscle release monitor was used to monitor the muscle relaxation effect. When the muscle relaxation recovered to 25%, the rocuronium 0.15 mg / kg 路kg ~ (-1) of rocuronium was added. Record changes in vital signs from induction to end of anesthesia. The onset time of rocuronium bromide was recorded, the muscle release time was 25% and the recovery time was 90%. The venous blood samples were collected from the subjects. The genotypes of OATP 1B 1, MDR1 and CHRNA1 were analyzed by polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) and polymerase chain reaction (PCR). The parameters of different genotypes were compared by univariate analysis of variance and chi-square test, and the independent factor analysis of effect of rocuronium on the efficacy of rocuronium was analyzed by single factor regression analysis. Multivariate regression analysis was used to analyze the effect of rocuronium on different factors. Results the ratio of different genotypes to the total number of people was 10 in AA group, 10 in AG group, 37 in GG group, 53 in ATP 1B1521T / C genotype in TT group, 80T group in TC group, 18C group in TC group, 2MDR11236CT genotype in TT group, 49.5T% in CT group, respectively. 37.5 the proportion of different genotypes of MDR13435C / T to the total number of people was 41.5 in CC group and 19.5T in CT group. The proportion of different genotypes of CHRNA1rs168628A / G to the total number of people was 91rs168628A / G in AA group 91rs168628A / G group, respectively, in AA group 91rs168628A / G group: AA group 91rs168628A / G patients with different 2%.2OATP1B1388A/G genotypes in AA group 91GG group. Compared with AA group, the maintenance time of muscle relaxant dose and additional dose and the recovery time of muscle relaxation were longer in AG group and GG group than in AA group. The amount of muscle relaxant inducer and the maintenance time of additional dose were higher in TT group than in AA group with different genotypes of MDR11236C / T locus. The recovery time of muscle relaxation in CC and CT groups was longer than that in CC and CT groups. The patients with different genotypes of CHRNA1rs168628A/G, MDR13435C / T, MDR13435C / T, were also longer than those of CC and CT patients with different genotypes of OAT1B1521T / C, MDR13435C / T, CHRNA1rs168628A/G. There was no significant difference in muscle relaxation effect (P 0.05). Conclusion the clinical effect of OATP1B1388AG and MDR11236CT gene polymorphisms on rocuronium is limited, suggesting that genetic factors may be one of the reasons leading to individual differences in the efficacy of musculus relaxants. Conclusion: the clinical effects of OATP1B1388AG gene polymorphisms on rocuronium C / C, MDR13435C / T, CHRNA1rs168628A/G gene polymorphisms are limited, while OATP1B1388AG and MDR11236CT gene polymorphisms can influence the muscle relaxation effect of rocuronium.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R614

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