本文選題：遺傳藥理學(xué) + 基因多態(tài)性��； 參考：《中南大學(xué)》2014年碩士論文

【摘要】：目的：觀察OATP1B1, MDR1和CHRNA1基因多態(tài)對全麻病人圍術(shù)期肌松藥羅庫溴銨肌松效應(yīng)的影響。 方法：全麻下行擇期耳鼻喉科手術(shù)患者207例,ASA I或Ⅱ級,18-59歲。麻醉誘導(dǎo)方案：依次靜注咪唑達侖0.06mg/kg,舒芬太尼0.7u g/kg,丙泊酚1mg/kg,羅庫溴銨0.6mg/kg;麻醉維持方案：靶控輸注丙泊酚(血漿靶濃度3-5μg/ml,)和瑞芬太尼(效應(yīng)室靶濃度3～6ng/ml)。整個過程用TOF-Watch SX型加速度肌松監(jiān)測儀監(jiān)測肌松效應(yīng),肌松恢復(fù)到25%時追加羅庫溴銨0.15mg/kg。記錄從誘導(dǎo)開始到麻醉結(jié)束患者生命體征的變化。記錄羅庫溴銨的起效時間、肌松恢復(fù)到25%時間、恢復(fù)到90%時間。抽取受試者的靜脈血2m1,采用聚合酶鏈反應(yīng)一限制性片段長度多態(tài)性(PCR-RFLP)的方法對患者OATP1B1, MDR1和CHRNA1進行基因型分析。計量資料應(yīng)用X±SD表示；不同基因型之間參數(shù)的比較采用單因素方差分析和卡方檢驗,影響羅庫溴銨作用時效的獨立因素分析采用單因素回歸分析；不同影響因素與羅庫溴銨作用時效的分析采用多因素回歸分析。 結(jié)果：①OATPIBI388A/G不同基因型占總?cè)藬?shù)的比例分別是AA組10%,AG組37%,GG組53%；OATP1B1521T/C不同基因型占總?cè)藬?shù)的比例分別是TT組80%,TC組18%,CC組2%;MDR11236C/T不同基因型占總?cè)藬?shù)的比例分別是CC組13%,CT組49.5%,TT組37.5%；MDR13435C/T不同基因型占總?cè)藬?shù)的比例分別是CC組41.5%,CT組39%,TT組19.5%；CHRNA1rs168628A/G不同基因型占總?cè)藬?shù)的比例分別是AA組91%,AG組8%,GG組2%。②OATP1B1388A/G不同基因型的患者,相對于AA組而言,AG組和GG組肌松誘導(dǎo)劑量和追加劑量的維持時間以及肌松恢復(fù)時間均更長(P0.05)；MDR11236C/T位點不同基因型的患者,TT組肌松誘導(dǎo)劑量和追加劑量的維持時間均比CC和CT更長(P0.05),TT組肌松恢復(fù)時間比CC和CT組也更長(P0.05)；OATP1B1521T/C, MDR13435C/T, CHRNA1rs168628A/G不同基因型的患者,肌松效應(yīng)沒有顯著差異(P0.05)。 結(jié)論：OATP1B1521T/C, MDR13435C/T, CHRNA1rs168628A/G基因多態(tài)性多羅庫溴銨的臨床作用時間的影響有限,而OATP1B1388AG和MDR11236CT基因多態(tài)性可影響羅庫溴銨的肌松效應(yīng),提示遺傳因素是導(dǎo)致肌松藥藥效個體差異的原因之一。
[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.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R614

【參考文獻】

相關(guān)期刊論文 前1條

1 ;Organic anion transporting polypeptide-1B1 haplotypes in Chinese patients[J];Acta Pharmacologica Sinica;2007年10期

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本文編號：1857499