急性有机磷酸酯类化合物中毒对大鼠神经元的损伤作用

Effect of organophosphate-induced acute neuronal damage in rats

目的探讨有机磷酸酯类化合物对大鼠神经元的急性损伤作用及其可能的机制。方法18只SD大鼠按照随机数字表法分为2组，分别是染毒组（12只）和对照组（6只）。染毒组选择沙林作为有机磷酸酯类化合物代表，大鼠肌肉注射沙林，1min后腹腔注射氯解磷定和阿托品，山现典型中毒症状者入组：对照组在相应时间点给予注射生理盐水。24h后取脑组织行HE染色、神经元核抗原（NeuN）免疫组化酶染色分析，观察大鼠脑组织梨状皮质、海马CAl区、纹状体区神经元的变化。结果HE染色发现中毒大鼠梨状皮质、纹状体区可见较多变性、坏死的神经细胞。并且NeuN阳性细胞数明显减少．与对照组相比差异有统计学意义（P〈0．05）。结论在急性大剂量有机磷酸酯类化合物暴露情况下。可以引起大鼠神经元的大量坏死，从而产生一系列的神经功能缺损。这种作用可能与细胞毒性作用、氧化应激等非胆碱能机制有关。

Objective To evaluate the neuronal injury induced by organophosphorus （OP） compound exposure in rats and investigate and the possible mechanisms. Methods Eighteen SD rats were randomly divided into OP groups （n=12） and the control group （n=6）. SD rats were given intramuscular satin injection followed 1 min later by intraperitoneal injection of atropine sulphate and pralidoxime, and the rats with typical toxic reactions were used for subsequent experiment. The rats in the control group received normal saline injections in identical manners. Twenty-four hours later, the brain tissue of the rats were taken for HE staining and neuronal nuclei antigen （NeuN） immunohistochemistry to quantitatively assess the neuronal damages in the pyriform cortex, hippocampus CA1 and striatum. Results HE staining showed massive degeneration of the neurons in the pyriform cortex, hippocampus CAland striatum of rats with satin injection. Compared to the rats with saline injections, the rats exposed to satin presented with significantly decreased number of NeuN-positive neurons （P〈0.05）. Conclusion OP can induce acute neuronal death in rat brain and cause a series of symptoms in the central nervous system, probably by such noncholinergic mechanisms as glutamic acid-induced cytotoxicity and oxidative stress.