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目的:探讨多药耐药基因1(MDR1)C3435T多态性对关节置换术后镇痛药物(地佐辛联合舒芬太尼)使用量的影响。方法:选取2014年1月-2016年2月在天津市人民医院和天津港口医院行关节置换术的患者300例,术后给予地佐辛+舒芬太尼联合镇痛。采用聚合酶链反应-限制性片段长度多态性分析法测定其MDR1 C3435T多态性,比较不同基因型患者术后视觉模拟量表(VAS)评分、镇静程度(Ramesy)评分、地佐辛+舒芬太尼的使用量,以及不良反应发生情况。结果:300例患者中,MDR1 C3435T CC、CT和TT基因型分别有100例(33.3%)、102例(34.0%)和98例(32.7%),各基因型频率均符合Hardy-Weinberg平衡(P>0.05)。各基因型患者术后0、24、48 h VAS评分、Ramesy评分比较,差异均无统计学意义(P>0.05),且未见镇静过度者。CT、TT基因型患者术后0~24、>24~48 h地佐辛+舒芬太尼的使用量均显著低于CC基因型患者,差异均有统计学意义(P<0.05);而CT与TT基因型上述各时间段药物使用量比较,差异均无统计学意义(P>0.05)。TT基因型患者术后恶心呕吐(PONV)及总体不良反应发生率均显著低于CC、CT基因型患者,差异均有统计学意义(P<0.05);而CC与CT基因型患者PONV及总体不良反应发生率,以及各基因型患者瘙痒的发生率比较,差异均无统计学意义(P>0.05)。结论:在达到相似镇痛、镇静效果的前提下,MDR1 C3435T突变型患者对地佐辛+舒芬太尼的耐受性更低,所需剂量更少,且不良反应发生率更低。该基因型可作为临床个体化治疗的参考指标。
OBJECTIVE: To investigate the effects of multidrug resistance gene 1(MDR1) C3435T polymorphism on the dose of analgesia agents (dezocine combined with sufentanil) after joint replacement. METHODS: 300 patients receiving joint replacement were selected from Tianjin People’s Hospital and Tianjin Port Hospital during Jan. 2014-Feb. 2016. They were given dezocine and sufentanil for postoperative analgesia. PCR-RFLP was used to determine MDR1 C3435T polymorphism; VAS scores, Ramesy scores, the dose of dezocine+sufentanil and the occurrence of ADR were compared among different genotypes. RESULTS: Among 300 patients, there were 100 (33.3%), 102 (34.0%) and 98 (32.7%) cases of MDR1 C3435T CC, CT and TT genotype, respectively, the frequencies of which were all in line with Hardy-Weinberg balance (P>0.05). There was no statistical significance in VAS scores and Ramesy scores among different genotypes 0, 24, 48 h after surgery (P>0.05). No excessive sedation was found. The dose of dezocine+sufentanil in CT and TT genotype were all significantly lower than CC genotype 0-24 h, >24-48 h after surgery, with statistical significance (P<0.05). There was no statistical significance in drug dose between CT and TT genotype during above periods (P>0.05). The incidence of postoperative nausea and vomiting (PONV), ADR in TT genotype were significantly lower than CC and CT genotypes, with statistical significance (P<0.05). There was no statistical significance in the incidence of PONV and ADR between CC genotype and CT genotype, and in the incidence of itch among different genotypes (P>0.05). CONCLUSIONS: With similar sedation and analgesic effect, MDR1 mutant type have lower resistance to dezocine+sufentanil, and smaller drug dose is need, the incidence of ADR is lower. MDR1 genotype can be regarded as an important indicator of clinical individualized treatment.
MDR1基因多态性关节置换术术后镇痛地佐辛舒芬太尼使用量VAS评分Ramesy评分
MDR1Gene polymorphismJoint replacementpostoperative analgesiaDezocineSufentanilDoseVAS scoreRamesy score
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