鱼藤酮长期作用对大鼠纹状体单胺递质、NO和NOS的影响

Effects of long-term rotenone intoxication on the monoamine neurotransmitters, NO, and NOS in rat striatum

目的 观察鱼藤酮长期作用对大鼠纹状体单胺递质和NOS NO系统的变化规律。方法 Wistar大鼠每日皮下注射鱼藤酮 90d ,于第 3 0、60、90天处死动物 ,分离大鼠纹状体 ,分别以HPLC法和生化法测定其多巴胺 (DA)、去甲肾上腺素 (NA)、3 ,4 二羟基苯乙酸 (DOPAC)、5 羟色胺 ( 5 HT)、一氧化氮 (NO)含量和一氧化氮合酶 (NOS)活性。结果 在鱼藤酮中毒各时相点 ,大鼠纹状体单胺递质均出现不同程度的变化 ,以DA、DOPAC、5 HT含量改变尤为明显 ;纹状体NO含量和NOS活性均明显升高 ,且中毒剂量越大、中毒时间越长NO、NOS升高越明显。结论 纹状体单胺递质代谢紊乱和NOS NO系统改变在鱼藤酮长期作用引起的中枢DA神经损伤中起重要作用。

Objective To observe the changes of monoamines, nitric oxide (NO), and nitric oxide synthase (NOS) in rat striatum induced by long-term rotenone intoxication. Methods Wistar rats were daily administrated with rotenone at the doses of 0.335, 0.670, and 1.005 mg/kg (sc). Animals were sacrificed on days 30, 60 and 90. High performance liquid chromatography (HPLC) and photoelectric colorimetry were used to determine the concentrations of noradrenaline (NA), dopamine (DA), dihydroxyphenylaceticacid (DOPAC), 5-hydroxytryptamine (5-HT), NOS, and NO in the striatum, respectively. Results At each time point, rotenone induced significant changes of monoamines at various levels, especially the contents of DA, DOPAC, and 5-HT in the rat striatum. NO concentration and NOS activity in rat striatum increased remarkably in dose- and time-dependent manners. Conclusion The metabolic disturbance of monoamine neurotransmitters and NOS/ NO system in the rat striatum plays an important role in the central DA nerve injury induced by long-term rotenone intoxication.