金钗石斛提取物对秀丽隐杆线虫帕金森病模型的神经保护作用研究
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1.西南医科大学附属中医医院中葡中医药国际合作中心;2.中国农业科学院农产品加工研究所;3.山东大学齐鲁医学院基础医学院生理教研室;4.葡萄牙米尼奥大学生物系,分子和环境生物学中心,中葡药食植物资源研究中心,葡萄牙 布拉加 4710-057


Neuroprotective effect of Dendrobium nobile Lindl extract on Caenorhabditis elegans model of Parkinson"s disease
Author:
Affiliation:

1.Sino-Portugal TCM International Cooperation Center,the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University;2.Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193.;3.Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong,250012;4.Sino-PT Research Center for Medicinal and Food Plant Resources, Centre of Molecular and Environmental Biology(CBMA), Department of Biology, University of Minho,4710-057, Braga, Portugal.

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    摘要:

    目的 为了研究金钗石斛(Dendrobium nobile Lindl,DNL)对帕金森病秀丽隐杆线虫模型的影响,用6-OHDA诱导帕金森病线虫模型,用DNL对线虫进行干预。方法 分别用7.5、15、30mg/L的DNL提取物对转基因模型秀丽隐杆线虫NL5901和经6-OHDA诱导的N2、 BZ555、PD4521及BC7272 线虫进行处理,分别观测线虫生存率、基础减慢反应率、α-突触核蛋白(alpha-synuclein, α-syn)聚集情况、多巴胺能神经元(dopaminergic neurons,DNs)情况、体壁肌肉细胞线粒体分布密度及膜内蛋白水平。检测经6-OHDA诱导的N2线虫体内SOD、GSH活性,探究DNL对帕金森病线虫模型的抗氧化应激能力的作用。结果 与未经DNL处理的PD模型线虫相比,PD模型线虫经DNL及L-DOPA处理后线虫DNs荧光强度明显增强(P<0.001),α-syn聚集明显减少(P<0.05或P<0.001),基础减慢率均增加(P<0.05或P<0.001),线粒体密度增(P<0.001),线粒体内膜蛋白含量增加(P<0.05或P<0.001),并且SOD含量增加(P<0.05),GSH含量也呈上升趋势;在寿命试验中,N2野生型线虫和两种PD线虫经DNL处理后均有寿命延长(P<0.05或P<0.001)。结论 一定浓度的DNL能有效改善秀丽隐杆线虫帕金森病模型的运动麻痹,改善DNs退化,抑制α-syn的聚集和神经元的损伤,增加抗氧化应激能力,减缓线虫衰老过程。此结果为帕金森病有效药物的筛选提供参考。

    Abstract:

    Objective To investigate the effect of Dendrobium nobile Lindl (DNL) on Caenorhabditis elegans (C. elegans) model of Parkinson"s disease, 6-OHDA was used to induce C. elegans model of Parkinson"s disease(PD), and Dendrobium nobile was used to interfere with C. elegans. Methods C. elegans NL5901 and 6-OHDA-induced N2, BZ555, PD4521 and BC7272 were treated with DNL of 7.5, 15 and 30mg/L. The survival rate, basal slowing response rate, α-synuclein aggregation(α-syn), dopaminergic neurons(DNs), mitochondrial distribution density of body wall muscle cells and protein levels in the membrane were observed. In addition, the activity of SOD and GSH in 6-OHDA-induced N2 was detected to explore the effect of DNL on the anti-oxidative stress ability of Parkinson disease C. elegans models. Results Compared with the PD model group, the DNs fluorescence intensity of the nematodes treated with DNL and L-DOPA was significantly increased (P<0.001), α-syn aggregation was significantly decreased (P<0.05 or P<0.001), the basal slowing rate was increased (P<0.05 or P<0.001), mitochondrial density was increased (P<0.001), mitochondrial intima protein content was increased (P<0.05 or P<0.001), SOD(P<0.05) and GSH content are also increased. The lifespans of N2 wild type C. elegans and PD C. elegans models were prolonged after DNL treatment (P<0.05 or P<0.001). Conclusions A certain concentration of DNL can effectively improve the paralysis of C. elegans model of Parkinson"s disease, improve the degeneration of dopaminergic neurons, reduce the accumulation of α-syn and suppressed the loss of DNs. Overall, DNL treatment increase the ability of anti-oxidative stress, and slow down the aging process of C. elegans. These results provide reference for the screening of effective drugs for Parkinson"s disease.

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  • 收稿日期:2024-11-28
  • 最后修改日期:2024-12-10
  • 录用日期:2025-02-18
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