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黄连多糖对阿尔茨海默病转基因秀丽隐杆线虫模型中β淀粉样蛋白(Aβ)诱导毒性的神经保护作用。

Neuroprotective effects of Coptis chinensis Franch polysaccharide on amyloid-beta (Aβ)-induced toxicity in a transgenic Caenorhabditis elegans model of Alzheimer's disease (AD).

机构信息

Department of Traditional Chinese Medicine, Shanghai Pudong Hopstital, Fudan University Pudong Medical Center, Shanghai 201399, China; Chuangchun University of Chinese Medicine, Changchun, Jilin 130117, China.

School of Life Science, Jilin University, Changchun 130012, China.

出版信息

Int J Biol Macromol. 2018 Jul 1;113:991-995. doi: 10.1016/j.ijbiomac.2018.03.035. Epub 2018 Mar 7.

DOI:10.1016/j.ijbiomac.2018.03.035
PMID:29524490
Abstract

This study aims to investigate the neuroprotective effects of Coptis chinensis Franch polysaccharide (CCP) on Aβ transgenic CL4176 Caenorhabditis elegans, as well as its mechanism of action. The results in life span experiment showed that CCP could significantly increase the lifespan of C. elegans and the effect is in the descending order of 100mg/L>500mg/L>200mg/L. The behavioral experiments also demonstrated that CCP at the concentration of 100mg/L could delay the paralysis rate of C. elegans, which was significantly different from the control group. In terms of Aβ toxicity in C. elegans, morphological observation using Thioflavin S staining method indicated that the deposition of Aβ protein in the head area of the untreated C. elegans was much more than those in the CCP (100mg/L)-treated CL4176. In line with this finding, fluorogenic quantitative real-time PCR confirmed that the transcriptional levels of HSP16.2 (Y46H3A.D) and HSP16.41 (Y46H3A.E) in C. elegans was 21 times and 79 times higher than those in untreated control. Thus, these data demonstrate that CCP could reduce Aβ-induced toxicity by delaying the aging, decreasing the rate of paralysis, inhibiting the deposition of Aβ, and increasing the expression levels of HSP genes in transgenic C. elegans.

摘要

本研究旨在探讨黄连多糖(CCP)对 Aβ 转基因 CL4176 秀丽隐杆线虫的神经保护作用及其作用机制。寿命实验结果表明,CCP 能显著延长秀丽隐杆线虫的寿命,且作用效果呈 100mg/L>500mg/L>200mg/L 的下降趋势。行为学实验也表明,100mg/L 的 CCP 能延缓秀丽隐杆线虫的麻痹率,与对照组相比差异有统计学意义。在 Aβ 对秀丽隐杆线虫的毒性方面,采用硫黄素 S 染色法进行形态学观察发现,未经处理的秀丽隐杆线虫头部 Aβ 蛋白的沉积量明显多于 CCP(100mg/L)处理的 CL4176。与之相符的是,荧光定量实时 PCR 证实秀丽隐杆线虫中 HSP16.2(Y46H3A.D)和 HSP16.41(Y46H3A.E)的转录水平分别比未经处理的对照组高 21 倍和 79 倍。因此,这些数据表明 CCP 可通过延缓衰老、降低麻痹率、抑制 Aβ 沉积以及增加转 Aβ 秀丽隐杆线虫中 HSP 基因的表达水平来减轻 Aβ 诱导的毒性。

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