左旋多巴对帕金森病大鼠黑质多巴胺能神经元及纹状体多巴胺递质的影响

目的　研究长期应用左旋多巴对帕金森病 (PD)大鼠黑质多巴胺 (DA)能神经元和DA递质的影响。方法　采用 6 羟基多巴胺 (6 OHDA)制备部分损毁和严重损毁的PD大鼠模型 ,给两种模型口服不同剂量左旋多巴 /苄丝肼 3个月 ,通过观察大鼠旋转行为、酪氨酸羟化酶 (TH)免疫组化染色和高效液相色谱 电化学检测仪 (HPLC ECD)检测纹状体单胺类递质 ,研究左旋多巴对PD大鼠残存的黑质DA能神经元的影响。结果　 (1)左旋多巴对PD大鼠的旋转行为无明显影响 ;(2 )TH阳性细胞数损毁侧 /非损毁侧比值在左旋多巴喂药组和不喂药对照组的差异无显著意义 (P >0 0 5 ) ;(3)在严重损毁组 ,大剂量左旋多巴使PD大鼠损毁侧DA和 3,4二羟基苯乙酸 (DOPAC)水平明显升高(P <0 0 1)。结论　长期使用左旋多巴对 6 OHDA单侧损毁的PD大鼠残存的黑质DA能神经元无毒性作用。

Effects of chronic levodopa administration on dopaminergic neurons and dopamine transmitter in Parkinsonian rats

Objective To investigate the effects of three-month levodopa administration on dopaminergic neurons and dopamine transmitter in parkinsonian rats. Methods Different doses of levodopa/benserazide were treated orally for three months in rats with 6-OHDA-induced partial or severe injuries of unilateral nigrostriatal pathway. The effects of levodopa on the remaining dopaminergic neurons in the substantia nigra were studied by the methods of rotational behavior, tyrosine hydroxylase (TH) immunohistochemical assays and high performance liquid chromatography (HPLC). Results No obvious behavioral changes were observed after levodopa treatment. No significant difference was found in the number of TH-positive cells in 6-OHDA-lesioned side over the non-lesioned side in substantia nigra between levodopa-treated and non-treated rats (P>0.05). The contents of striatal dopamine and DOPAC were far more increased in levodopa-treated rats with a high dose than in levodopa-treated rats with a low dose and in saline-treated rats (P<0.01). Conclusion It suggests that a three-month oral levodopa treatment should be not toxic for the remaining dopaminergic neurons in rats with a unilateral 6-OHDA lesion.