吗啡镇痛个体差异的遗传药理学进展

发布时间：2018-06-22 20:27

本文选题：吗啡镇痛 + 个体差异　；参考：《中国比较医学杂志》2017年10期

【摘要】：吗啡是广泛使用的一种阿片类镇痛药,不同个体间对吗啡镇痛的敏感性有较大差异,长期使用吗啡会导致镇痛效果降低而产生耐受,耐受的易感性在个体间也有较大差异,这些都给吗啡在临床的优化应用带来很多困扰。遗传因素通过控制蛋白质编码从药代动力学和药效动力学两方面影响个体对吗啡镇痛的反应。P-糖蛋白编码基因ABCB1的多样性影响吗啡的转运和分布,编码UDP-葡糖醛酸转移酶的基因UGT2B7的多样性则控制吗啡代谢转化。吗啡的主要作用靶点μ阿片受体的编码基因OPRM1和儿茶酚-O-甲基转移酶的编码基因COMT的多样性引起的下游信号通路反应性差异影响吗啡镇痛药效学。未来对吗啡镇痛个体差异的遗传学研究需要使用遗传多样性更复杂的个体,采用更系统全面的分析方法从更广的范围筛选关键基因。阐明遗传多样性与个体间对吗啡镇痛反应差异的关系,将有助于理解吗啡镇痛的遗传药理学调控机制,为临床吗啡镇痛使用实现个人化、精确化甚至联合基因治疗改善吗啡镇痛提供依据。
[Abstract]:Morphine is a widely used opioid analgesics. There are great differences in the sensitivity of morphine analgesia among different individuals. Long-term use of morphine leads to a decrease in analgesic effect and tolerance, and the susceptibility to tolerance is also different among individuals. These all bring a lot of troubles to the optimization of the clinical application of morphine. Genetic factors affect the transport and distribution of morphine by controlling protein coding in pharmacokinetic and pharmacokinetic aspects. The diversity of ABCB1 gene affects the response of individuals to morphine analgesia. The diversity of UGT2B7, a gene encoding UDP- glucuronyltransferase, controls the metabolic transformation of morphine. The diversity of the encoding gene OPRM1 of the 渭 opioid receptor and the COMT gene of catechol-O-methyltransferase caused the difference of downstream signal pathway reactivity in morphine analgesic pharmacodynamics. Future genetic studies on individual differences in morphine analgesia require the use of individuals with more complex genetic diversity and a more systematic and comprehensive analysis method for screening key genes from a wider range. To elucidate the relationship between genetic diversity and individual analgesia response to morphine will be helpful to understand the genetic pharmacological mechanism of morphine analgesia and to realize individualization of morphine analgesia in clinic. Precision and even gene therapy can be used to improve morphine analgesia.
【作者单位】：中国医学科学院医学实验动物研究所北京协和医学院比较医学中心卫计委人类疾病比较医学重点实验室;
【基金】：[基金项目]中国医学科学院中央级公益性科研院所基本科研业务费(2016ZX310044)
【分类号】：R96

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