有机磷杀虫剂所致的神经肌接头病的生化机制研究

目的 探讨有机磷杀虫剂(OPs)引起的神经肌接头传导功能异常的生化机制。方法 用肟硫磷(1144mg／kg)染毒大鼠制作肌无力模型，用电刺激频率为20Hz的单纤维肌电图(SSFEMG)检测染毒大鼠平均连续差(MCD)评价其神经肌接头传导功能，检测排肠肌Ca2 -ATP酶、Na ，K -dP酶、cAMP依赖性蛋白激酶(PKA)、Ca2 ／磷脂依赖性蛋白激酶(PKC)和酪氨酸蛋白激酶(TPK)活力，并用免疫组织化学法检测比目鱼肌中丝氨酸(Ser)、苏氨酸(Thr)和酪氨酸(Tyr)残基的磷酸化程度。结果 与对照组和肌力正常的染毒大鼠相比，肌无力大鼠各指标的变化如下：(1)MCD明显增高；(2)排肠肌Ca2 -ATP醇、Na ，K -ATP酶和PKA活力明显下降，且与MCD呈显著负相关(r＝-0．582、-0．713、-0．505，P＜0．05)；(3)排肠肌PKC和TPK活力明显增高，且与MCD呈显著正相关(r＝0．723、0．589，P＜0．05)；(4)Ser磷酸化程度明显减弱，Tyr磷酸化程度明显增强。结论 OPs引起的神经肌接头传导功能异常可能与Caj -ATP酶和Na ，K -ATP酶活力下降引起的肌肉兴奋性减低，以及Tyr磷酸化增强和Ser磷酸化减弱引起的烟碱样乙配胆碱受体失敏加速、复敏延迟有关。

Potential biochemical mechanisms of neuromuscular junction transmission dysfunction induced by organophosphorus insecticides

Objective To explore the potential biochemical mechanisms of neuromuscular junction transmission(NMJT) dysfunction induced by organophosphorus insecticides. Methods Ten rats were dosed with phoxim(1 144 mg/kg) and 5 of them developed myasthenia.The NMJT function was evaluated by the mean consecutive differences(MCD) measured by stimulation single fiber electromyography(SSFEMG) with the frequency of stimuli at 20 Hz.The activity of Ca 2+ -ATPase,Na +,K +-ATPase,cAMP dependent protein kinase(PKA),Ca 2+ /phospholipid dependent protein kinase(PKC),and tyrosine protein kinase(TPK) were determined. Results In comparison with the control and non-myasthenic rats,the results in myasthenic rats showed that:(1)?the MCDs increased;(2)?the activities of Ca 2+ -ATPase,Na +,K +-ATPase and PKA decreased and were negatively correlated with MCD;(3)?the activities of PKC and TPK increased,and were positively correlated with MCD;(4)?the phosphorylation of serine residuals in sarcolemma was weaker and the phosphorylation of tyrosine residuals was stronger. Conclusions The NMJT dysfunction is likely associated with the decrease in Ca 2+ -ATPase and Na +,K +-ATPase activity.The acceleration of desensitization and prolongation of resensitization of nicotinic acetylcholine receptors occur following the increase in tyrosine phosphorylation and the decrease in serine phosphorylation induced by OPs poisoning.