文章摘要
倪锴文,陈亚玲,周林水,等.紫杉醇诱导周围神经病变的作用机制研究进展及中医辨治探讨[J].浙江中医药大学学报,2020,44(8):818-824.
紫杉醇诱导周围神经病变的作用机制研究进展及中医辨治探讨
Research Progress of the Mechanism of Paclitaxel-induced Peripheral Neuropathy and Discussion on Treatment Based on Syndrome Differentiation of Traditional Chinese Medicine
投稿时间:2020-02-14  
DOI:10.16466/j.issn1005-5509.2020.08.021
中文关键词: 紫杉醇  化疗  周围神经病变  单药  作用机制  研究进展  痹症  中医药治疗
英文关键词: paclitaxel  chemotherapy  peripheral neuropathy  single component  mechanism  research progress  numbnessi TCM treatment
基金项目:国家重点研发计划资助项目(2018YFC2002500);浙江省中药配方颗粒研究专项项目(2017ZKL007);浙江省医药卫生科研基金项目(2017KY506)
作者单位E-mail
倪锴文 浙江中医药大学 杭州 310053  
陈亚玲 浙江中医药大学 杭州 310053  
周林水 浙江中医药大学附属第一医院  
高润娣 浙江中医药大学附属第一医院  
王真 浙江中医药大学附属第一医院 wangzhen610@sina.cn 
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中文摘要:
      [目的]分析近10年来紫杉醇诱导周围神经病变(paclitaxel-induced peripheral neuropathy,PIPN)的作用机制,简述相关药物研究并进行中医辨治探讨。[方法]以“紫杉醇”“周围神经病变”为关键字,检索Pubmed、中国知网(China National Knowledge Infrastructure,CNKI)、Springer及万方数据库,筛选近10年来的中外文献,选出与主题高度契合的文章,简述PIPN的主要临床表现,PIPN的神经、细胞改变,简析与PIPN相关的炎症氧化过程、细胞信号转导异常、神经递质改变以及相关细胞的核转录异常,同时简述相应的药物研究,并在此基础上探讨中医辨治PIPN的可行性和优越性。[结果]共有133篇文献入选,与本文主题高度契合。PIPN的临床表现主要是双手和双足麻木疼痛、灼热感,病理表现主要为神经纤维变形、神经胶质细胞增多及线粒体功能障碍;诱发免疫应答和氧化应激,导致外周循环中的细胞因子及活性氧增加。紫杉醇主要通过以下方式诱发炎症氧化及相关的神经细胞改变:导致环腺苷酸(cyclic adenosine monophosphate,cAMP)通路、大麻素受体(cannabinoid receptor,CB)、磷脂酰肌醇3-激酶-蛋白激酶B-哺乳动物雷帕霉素靶点(phosphatidylinositol 3-kinase-protein kinase B-mammalian target of rapamycin,PI3K-AKT-mTOR)通路、p38丝裂原活化蛋白激酶(p38 mitogen activated protein kinase,p38MAPK)通路、N-甲基-D-天门冬氨酸(N-methyl-D-aspartate,NMDA)受体、静息电位、瞬时电流、钠离子通道、钾离子通道、钙离子通道、核转录因子-κB(nuclear factor-κB,NF-κB)及核因子红细胞2相关因子2-抗氧化反应元件(nuclear factor erythroid 2 related factor 2-antioxidant response element,Nrf2-ARE)通路等信号通路的转导异常;影响神经递质γ-氨基丁酸、神经生长因子、饥饿素、雌激素的浓度。针对上述机制,相关的药物研究主要集中在阿片类药物、抗惊厥药物、抗氧化剂及相应的信号通道抑制剂上。从中医角度来说,PIPN属于“痹症”“不仁”范畴,其病因病机为正气虚衰,加之外邪侵袭,使皮毛肌肉经络失于濡养和(或)气血运行受阻,治疗应以温阳通经、益气活血为大法。[结论]紫杉醇通过多种生化过程引起PIPN,本研究为西药靶向治疗PIPN提供理论依据,也为中医药辨治PIPN提供理论证明。
英文摘要:
      [Objective] To review the mechanism of paclitaxel-induced peripheral neuropathy(PIPN) in recent 10 years, briefly introduce related drugs and discuss about the treatment based on syndrome differentiation of traditional Chinese medicine(TCM).[Methods] Based on the Keywords of "Paclitaxel" and "peripheral neuropathy", the databases of Pubmed, China National Knowledge Infrastructure(CNKI), Springer and Wanfang were searched, and the Chinese and foreign literatures in the past 10 years were screened. This paper introduced the main clinical manifestations of PIPN, the changes of nerve and cells in PIPN, and enumerated the inflammatory oxidation, cell signal transduction, neurotransmitter and nuclear transcription related to PIPN, and briefly describes the corresponding drug research. Moreover, the feasibility and superiority of TCM in the treatment of PIPN were illustrated.[Results] A total of 133 articles were included, which were highly consistent with the theme of this paper. The main clinical manifestations of PIPN were numbness, pain and burning sensation of hands and feet. The main pathological manifestations included nerve fiber deformation, neuroglial cell proliferation and mitochondrial dysfunction, and induction of immune response and oxidative stress, which led to the increase of cytokines and reactive oxygen species in the peripheral circulation. Paclitaxel mainly induced inflammatory oxidation and related neuronal changes in following signaling pathway transductions: cyclic adenosine monophosphate(cAMP) signaling pathway, cannabinoid receptor(CB), phosphatidylinositol 3-kinase-protein kinase B-mammalian target of rapamycin(PI3K-AKT-mTOR) signaling pathway, p38 mitogen activated proteinkinase(p38MAPK) signaling pathway, N-methyl-D-aspartate(NMDA) receptor, resting potential, transient current, Na+ channel, K+ channel, Ca2+ channel,nuclear factor-κB(NF-κB) signaling pathway, nuclear factor erythroid 2 related factor 2-antioxidant response element(Nrf2-ARE) signaling pathway; affecting the concentration of neurotransmitter, such as γ-aminobutyric acid, nerve growth factor, ghrelin and estrogen.In view of the above mechanism, the related drug research focused on opioids, anticonvulsants, antioxidants and corresponding signaling pathway inhibitors. From the perspective of TCM, PIPN belonged to the category of "numbness" and "arthralgia". The etiology and pathogenesis of PIPN were the deficiency of healthy Qi as well as invasion of single or multiple exogenous pathogens, which leads toloss of nutrition of the skin, muscle and meridians and(or) blockage of the circulation of Qi and blood, resulting in numbness and pain of skin and muscle. Basically, the treatment of PIPN was warming Yang and dredging meridians, tonifying Qi and promoting blood circulation. [Conclusion] PIPN was caused through a variety of biochemical processes, this study provided a theoretical basis for targeted treatment of PIPN, and also provided theoretical proof for the treatment of PIPN by TCM syndrome differentiation.
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