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白皮杉醇缓解斑马鱼炎症反应的作用机制研究

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长期或过度的炎症反应会对人体造成严重伤害,发现小分子药物白皮杉醇(PCT)可以作为一种潜在的抗炎药物.采用活性氧(ROS)检测实验,发现在一定安全范围内,随着PCT浓度增 加,对斑马鱼炎症损伤缓解作用逐渐提高,缓解程度存在剂量依赖效应,表明PCT具有抗氧化作用.通过中性粒细胞和巨噬细胞标记的转基因斑马鱼系Tg(corola:GFP;lyz:Dsred),发现PCT对CuSO4造成细胞损伤及氧化应激诱导的炎症反应的影响,使用不同浓度PCT处理CuSO4诱导的神经性炎症斑马鱼,可见斑马鱼体内迁移至脊椎神经丘部位的中性粒细胞数量明显减少,表明PCT对炎症趋化的中性粒细胞聚集到损伤部位具有修复作用.同时,qPCR检测结果证明与单独使用CuSO4处理组相比,PCT处理可显著下调白细胞介素-6(IL-6)、环氧合酶2(COX-2)及肿瘤坏死因子α(TNF-α)等炎症标志基因的表达,从而保护斑马鱼免受CuSO4诱导的炎症损伤.显示PCT在模式生物斑马鱼中具有抗炎、抗氧化作用,对未来PCT作为抗炎药物奠定了理论基础.
Mechanisms of Piceatannol in Alleviating Inflammatory Injury in Zebrafish
Prolonged or excessive inflammatory responses can cause serious damage to the human body,and preliminary experiments have shown that the small molecule drug piceatannol(PCT)can be used as a potential anti-inflammatory drug.In this study,reactive oxygen species detection assay was used,and it was found that the alleviation of inflammatory injury in zebrafish gradually increased with the increase of PCT concentration within a certain safety range,and there was a dose-dependent effect on the degree of alleviation,indicating that PCT has an antioxidant effect.The effects on CuSO4-induced cellular damage or oxidative stress-induced inflammation were investigated by using neutrophil-and macrophage-labelled transgenic zebrafish line Tg(coro1a:GFP;lyz:Dsred),in which zebrafish with CuSO4-induced neuroinflammation were treated with different concentrations of PCT,and the number of neutrophils migrating to the site of the spinal neuronal hillock was significantly reduced,indicating that PCT has an antioxidant effect on the neuroinflammation.The number of neutrophils migrating to the site of vertebral neuromast was significantly reduced,indicating that PCT has a restorative effect on the aggregation of inflammatory chemotactic neutrophils at the site of injury.Meanwhile,the qPCR results demonstrated that PCT treatment significantly down-regulated the expression of inflammatory marker genes such as IL-6,COX-2 and TNF-α compared with the CuSO4 treatment group alone,thus protecting zebrafish from CuSO4-induced inflammatory injury.Our study demonstrated the anti-inflammatory and antioxidant effects of PCT in the zebrafish model organism,providing a theoretical basis for the future use of PCT as an anti-inflammatory drug.

ZebrafishPiceatannolAnti-inflammatoryCuSO4Mechanisms

刘矿、袁驰、颜家员、祖尧

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上海海洋大学 科技部海洋生物科学国际联合研究中心 上海 201306

上海海洋大学 水产种质资源发掘与利用教育部重点实验室 上海 201306

临港新片区海洋生物医药科技创新型平台 上海 201306

斑马鱼 白皮杉醇 抗炎 硫酸铜 作用机制

2024

中国生物工程杂志
中国科学院文献情报中心 中国生物技术发展中心 中国生物工程学会

中国生物工程杂志

CSTPCD北大核心
影响因子:0.589
ISSN:1671-8135
年,卷(期):2024.44(11)