中国中药杂志

2014, v.39(09) 1660-1665

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荜茇总生物碱对6-羟基多巴胺致帕金森病大鼠多巴胺能神经元损伤的保护作用研究
Protective effect of alkaloids from Piper longum in rat dopaminergic neuron injury of 6-OHDA-induced Parkinson's disease

郑丽;王浩;巴寅颖;刘浩龙;王萌;郭未蔚;吴霞;杨慧;
ZHENG Li;WANG Hao;BA Yin-ying;LIU Hao-long;WANG Meng;GUO Wei-wei;WU Xia;YANG Hui;School of Traditional Chinese Medicine,Capital Medical University;Beijing Institute of Neural Science,Capital Medical University;

摘要(Abstract):

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。
Objective: To discuss the protective effect of alkaloids from Piper longum(PLA) in rat dopaminergic neuron injury of 6-OHDA-induced Parkinson's disease and its possible mechanism. Method: The rat PD model was established by injecting 6-OHDA into the unilateral striatum with a brain solid positioner. The PD rats were divided into the PLA group(50 mg·kg-1·d-1),the madorpa group(50 mg·kg-1·d-1) and the model group,with 15 rats in each group. All of the rats were orally given drugs once a day for 6 weeks. Meanwhile,other 15 rats were randomly selected as the sham operation group,and only injected with normal saline in the unilateral striatum. The behavioral changes were observed with the apomorphine( APO)-induced rotation and rotary rod tests. The number of tyrosine hydroxylase( TH)-positive cells in rat substantia nigra and the density of TH-positive fibers in striatum were detected by tyrosine hydroxylase immunohistochemistry. The content of superoxide dismutase( SOD),glutathione peroxidase( GSH-Px), glutathione( GSH),catalase( CAT),malondialdehyde( MDA),nitric oxide( NO) and nitric oxide synthase( NOS) in rat substantia nigra and striatum were measured by the spectrophotometric method. Result: After being induced by APO,PD rats showed obvious rotation behaviors,with decreased time stay on rotary rod and significant reduction in the number of TH-positive cells in sustantia nigra and the density of TH-positive fibers in striatum. The activities of SOD,GSH-Px,CAT,the content of GSH and the total antioxidant capacity significantly decreased,whereas the activities of NOS and the content of MDA,NO significantly increased. PLA could significantly improve the behavioral abnormality of PD rats and increase the number of TH-positive cells in sustantia nigra and the density of TH-positive fibers in striatum. It could up-regulate the activities of SOD,GSH-Px,CAT,the content of GSH and the total antioxidant capacity,and decrease the content of NOS and the content of MDA,NO. Conclusion: Alkaloids from P. longum shows the protective effect in substantia nigra cells of 6-OHDA-induced PD model rats. Its mechanism may be related with their antioxidant activity.

关键词(KeyWords): 帕金森病;荜茇;生物碱;6-羟基多巴胺;抗氧化
Parkinson's disease;Piper longum;alkaloid;6-hydroxydopamine;antioxidant

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金面上项目(81073016);; 北京市教育委员会科技计划面上项目(KM201010025013);; 北京市人才强教项目(PHR201008402);; 北京市脑重大疾病重点实验室项目(2011NZDB03)

作者(Author): 郑丽;王浩;巴寅颖;刘浩龙;王萌;郭未蔚;吴霞;杨慧;
ZHENG Li;WANG Hao;BA Yin-ying;LIU Hao-long;WANG Meng;GUO Wei-wei;WU Xia;YANG Hui;School of Traditional Chinese Medicine,Capital Medical University;Beijing Institute of Neural Science,Capital Medical University;

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