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白藜芦醇可显著减少缺氧和氧化应激诱导的分离人胰岛细胞凋亡。

Significant reduction of apoptosis induced via hypoxia and oxidative stress in isolated human islet by resveratrol.

机构信息

Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Nutr Metab Cardiovasc Dis. 2020 Jun 25;30(7):1216-1226. doi: 10.1016/j.numecd.2020.04.011. Epub 2020 Apr 20.

Abstract

BACKGROUND AND AIMS

Successful islet transplantation as a promising treatment of diabetes type 1 is threatened with the loss of islets during the pre-transplant culture due to hypoxia and oxidative stress-induced apoptosis. Therefore, optimization of culture in order to preserve the islets is a critical point. In this study, we investigated the effect of resveratrol, as a cytoprotective agent, on the cultured human islets.

METHODS AND RESULTS

Isolated islets were treated with different concentrations of resveratrol for 24 and 72 h. Islets' viability, apoptosis, apoptosis markers, and insulin and C-peptide secretion, along with the production of reactive oxygen species (ROS), hypoxia inducible factor 1 alpha (HIF-1α), and its target genes in the islets were investigated. Our findings showed that the islets were exposed to hypoxia and oxidative stress after isolation and during culture. This insult induced apoptosis and decreased viability during 72 h. The presence of resveratrol significantly attenuated HIF-1α and ROS production, reduced apoptosis, promoted the VEGF secretion, and increased the insulin and C-peptide secretion. In this regard, resveratrol improved the islet's survival and function in the culture period.

CONCLUSIONS

Using resveratrol can attenuate the stressful condition for the islets in the pre-transplant culture and subsequently ameliorate their viability and functionality that lead to successful outcome after clinical transplantation.

摘要

背景与目的

成功的胰岛移植作为 1 型糖尿病的一种有前途的治疗方法,由于缺氧和氧化应激诱导的细胞凋亡,在移植前培养过程中胰岛会丢失。因此,优化培养以保存胰岛是一个关键点。在这项研究中,我们研究了白藜芦醇作为一种细胞保护剂对培养的人胰岛的作用。

方法和结果

分离的胰岛用不同浓度的白藜芦醇处理 24 和 72 小时。研究了胰岛的活力、凋亡、凋亡标志物以及胰岛素和 C 肽的分泌,以及胰岛中活性氧 (ROS)、缺氧诱导因子 1 阿尔法 (HIF-1α)及其靶基因的产生。我们的研究结果表明,胰岛在分离后和培养过程中会受到缺氧和氧化应激的影响。这种损伤在 72 小时内诱导细胞凋亡并降低活力。白藜芦醇的存在显著减弱了 HIF-1α和 ROS 的产生,减少了凋亡,促进了 VEGF 的分泌,并增加了胰岛素和 C 肽的分泌。在这方面,白藜芦醇改善了胰岛在培养期间的存活和功能。

结论

在移植前培养过程中使用白藜芦醇可以减轻胰岛的应激状态,从而提高其活力和功能,为临床移植后的成功结果铺平道路。

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