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有机磷农药中毒机制和治疗新进展

赵敏陈良宏张志刚金帅李聪   

  1. 作者单位:中国医科大学附属盛京医院急诊科,沈阳 110004
  • 出版日期:2014-11-01 发布日期:2014-11-06
  • 基金资助:

    卫生部国家临床重点专科建设项目(2012-649)

New progress in the mechanism and treatment of organic phosphorus pesticide poisoning

ZHAO MinCHEN Liang-hongZHANG Zhi-gangJIN ShuaiLI Cong.   

  1. Department of Emergency Medicine,the Affiliated Shengjing Hospital of China Medical University,Shenyang 110004,China
  • Online:2014-11-01 Published:2014-11-06

摘要:

世界范围内有机磷农药在农业方面广泛应用,有机磷农药中毒很常见。最新的研究发现,有机磷农药中毒机制除了乙酰胆碱酯酶失活外,有机磷可能改变线粒体呼吸链中呼吸作用和能量产生过程中酶的活性,如电子供应通路、呼吸链酶、线粒体呼吸、ATP产生、氧化应激、线粒体膜的改变、钙吸收、线粒体依赖的凋亡通路。并且发现高脂溶性,持续性乙酰胆碱酯酶抑制,突触后乙酰胆碱受体下调或失敏,突触后乙酰胆碱不能释放,肌细胞损伤、氧化应激、能量代谢和钙稳态的破坏这些因素综合在一起导致中间综合征的发生。反复神经刺激频率、肌肉病变类型可以估计中间综合征的发生率。红细胞胆碱酯酶可反映出对靶器官的影响程度,是有机磷农药中毒的生物标志物。阿托品与安定联合使用治疗有机磷农药中毒比单独应用阿托品或肟类更能降低病死率。抗氧化剂如维生素E和C、α-生育酚对有机磷诱导的线粒体功能障碍可能起到保护作用,提供电子和ATP可以恢复线粒体功能。新的方法如生物清除剂、血浆和(或)血清的碱化、作用弱的拮抗剂代替作用强的拮抗剂及广谱肟类将在有机磷农药中毒治疗方面显示很好的前景。

关键词: 有机磷, 线粒体

Abstract:

Abstract:Organophosphorous (OPs) pesticides are the most widely used pesticides in the agriculture.OPs poisoning happened very frequently.Mitochondria dysfunctions can be a target for OPs poisoning as a non-cholinergic mechanism of toxicity of OPs.Some toxicities of OPs are arisen from dysfunction of mitochondrial oxidative phosphorylation through alteration of enzyme activities on the electron supplying pathways,mitochondrial respiratory,ATP generation,oxidative stress,mitochondrial membrane changes,calcium uptake and mitochondrial-dependent cell apoptotic pathways.High lipid-solubility,occurrences of persistent acetylcholinesterase (AChE) inhibition,muscular cell injury,and oxidative stress are the most important pieces of evidence for involvement of intermediate syndrome (IMS) in OPs toxicity.Down regulation or desensitization of postsynaptic ACh receptors and failure of postsynaptic ACh release are involved in IMS.Evolution of alterations on repetitive nerve stimulation (RNS),type and frequency of muscle lesions can estimate the probability of the IMS.The erythrocyte ChE can reflect the influencing degree of the target organ and is a biomarker of OPs poisoning.The combined use of atropine and diazepam in treatment of OPs poisoning can reduce the mortality rate more than single application of atropine or oxime.The mitochondrial dysfunction induced by OPs can be restored by use of antioxidants such as vitamin E and C,alpha-tocopherol,electron donors,and through increasing the cytosolic ATP level.New approaches to acute OPs poisoning treatment have a good future,including the bioscavenger,alkalinisation of blood plasma and(or) serum,use of weak inhibitors against strong inhibitors and novel broadspectrum oxime.

Key words: organophosphorous, mitochondria

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