慢性鱼藤酮中毒诱导的细胞凋亡机制初步探讨

目的观察小剂量鱼藤酮长期暴露对大鼠纹状体一氧化氮（nitricoxide,NO）、细胞色素C（cytochromeC,Cyt-C）含量及Caspase-3蛋白表达的影响,探讨鱼藤酮诱导的中脑多巴胺神经元凋亡机制。方法采用Wistar大鼠72只,随机分为对照组、鱼藤酮中毒0.335mg/kg、0.670mg/kg、1.005mg/kg组,连续皮下注射鱼藤酮30d、60d和90d,以生化法和Western-blotting法检测大鼠纹状体Cyt-C含量及Caspase-3蛋白的表达。结果小剂量鱼藤酮长期中毒可导致大鼠纹状体内NO和Cyt-C含量增加（P〈0.05）,且呈时间—剂量效应关系。Westernblotting结果证实小剂量鱼藤酮重复注射可导致纹状体Caspase-3蛋白表达增强。结论低剂量鱼藤酮重复注射可使动物脑组织NO、Cyt-C含量增高及Caspase-3蛋白表达增强,NO介导的细胞凋亡机制可能参与了鱼藤酮中毒所致的多巴胺神经元死亡。

Mechanism of apoptosis induced by chronic rotenone administration

Objective To observe the effect of low-dose rotenone with long term exposure on rats striatum NO concentration,cytochrome C content and Caspase-3 protein expression,and to explore the mechanism of rotenone-induced mesencephalic dopaminergic neuron apoptosis.Methods 72 Wistar rats were randomly divided into four groups,including control,0.335 mg/kg,0.670 mg/kg and 1.005 mg/kg group.All of the above rats were daily administrated with rotenone(SC)for 30 d,60 d and 90 d.Biochemistry assay and Western-blotting method were employed to detect the concentration of NO,cytochrome C and the expression of Caspase-3 protein,respectively.Results Long-term exposure to low dose rotenone could result in the elevation of NO and cytochrome C concentration(P<0.05)in rats brain tissue striatum with time-dose dependent relationship.Western-blotting results demonstrated that long term exposure to low-dose rotenone leads to the enhanced expression of caspase-3 protein in rats striatum.Conclusions Long term exposure to low-dose rotenone may lead to the increase of NO,cytochrome C concentration and the enhancement of caspase-3 expression in rats striatum.The apoptotic mechanism mediated by NO may be involved in the process of rotenone-induced dopaminergic neuron death.