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目的:探讨荜茇总生物碱(PLA)对6-羟基多巴胺(6-OHDA)致帕金森病(PD)大鼠多巴胺能神经元损伤的保护作用及其可能的机制。方法:采用脑立体定位单侧纹状体注射6-OHDA建立大鼠PD模型,将PD大鼠随机分为PLA组(PLA50 mg·kg-1·d-1),美多巴组(美多巴50 mg·kg-1·d-1)及模型组,每组15只,每日灌胃给药1次,连续6周。另随机选取15只大鼠在纹状体仅注射生理盐水作为假手术组。采用阿朴吗啡(APO)诱导的大鼠旋转及转棒实验进行行为学观察,酪氨酸羟化酶(TH)免疫组化检测大鼠黑质中TH阳性细胞数及纹状体中TH阳性纤维密度,用分光光度法检测大鼠黑质及纹状体内超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、还原型谷胱甘肽(GSH)、过氧化氢酶(CAT)、丙二醛(MDA)、一氧化氮(NO)及一氧化氮合酶(NOS)的含量。结果:帕金森病大鼠在APO诱导后出现明显的旋转行为,且在转棒上的滞留时间缩短,黑质区TH阳性细胞数及纹状体TH阳性纤维密度明显减少,组织内SOD,GSH-Px,CAT的活力降低,NOS的活力升高,MDA,NO含量升高,GSH含量降低,总抗氧化能力明显降低。PLA能明显改善PD大鼠的行为学异常,增加黑质区TH阳性细胞数及纹状体TH阳性纤维密度,提高组织内SOD,GSH-Px,CAT的活力,降低NOS的活力,降低MDA和NO含量,提高GSH含量,总抗氧化能力明显提高。结论:荜茇总生物碱对6-OHDA致PD模型大鼠的黑质细胞具有保护作用,其机制可能与抗氧化活性有关。
AIM: To investigate the protective effect of total alkaloid (PLA) on dopaminergic neuron damage induced by 6-hydroxydopamine (6-OHDA) in Parkinson’s disease (PD) rats and its possible mechanism. Methods: PD model was established by stereotactic injection of 6-OHDA into unilateral striatum. The PD rats were randomly divided into PLA group (PLA 50 mg · kg -1 · d -1) Pakistan 50 mg · kg-1 · d-1) and model group, 15 rats in each group. The rats were given gavage once a day for 6 weeks. Another 15 randomly selected rats in the striatum only saline as a sham group. Behavioral observation was performed with apomorphine (APO) -induced rat rotation and rotarod test. The number of TH-positive cells in the substantia nigra and the positive TH in the striatum were detected by tyrosine hydroxylase (TH) immunohistochemistry. Fiber density, the contents of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and reduced glutathione (GSH) in the substantia nigra and striatum of rats were measured by spectrophotometry (CAT), malondialdehyde (MDA), nitric oxide (NO) and nitric oxide synthase (NOS) were measured. Results: After the induction of APO, Parkinson ’s disease rats showed obvious rotation behavior, and the residence time on the rotating rod was shortened. The number of TH positive cells and the density of TH - positive striatum in substantia nigra were significantly decreased. The activities of SOD, GSH -Px, CAT decreased vitality, NOS activity increased, MDA, NO content increased, GSH content decreased, total antioxidant capacity decreased significantly. PLA can significantly improve the behavioral abnormalities in PD rats, increase the number of TH-positive cells in substantia nigra and striatum TH positive fiber density, increase the activity of SOD, GSH-Px and CAT in the tissue, decrease the activity of NOS and decrease the MDA and NO content, increase GSH content, total antioxidant capacity increased significantly. CONCLUSION: Total alkaloids from S. scrofa have a protective effect on substantia nigra cells induced by 6-OHDA in PD model rats, and its mechanism may be related to antioxidant activity.