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白藜芦醇通过 SIRT1/FOXO3a 和 PI3K/AKT 信号通路减轻放射性肠炎。

Resveratrol attenuates radiation enteritis through the SIRT1/FOXO3a and PI3K/AKT signaling pathways.

机构信息

Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Department of Oncology, Institute of Integrative Oncology, Tianjin Union Medical Center of Nankai University, Tianjin, China.

出版信息

Biochem Biophys Res Commun. 2021 May 21;554:199-205. doi: 10.1016/j.bbrc.2021.03.122. Epub 2021 Mar 31.

DOI:10.1016/j.bbrc.2021.03.122
PMID:33812084
Abstract

Radiation enteritis (RE) is the most common radiotherapy complication, and effective RE treatments are lacking. Resveratrol exerts beneficial effects on radiation injury. However, the effect of resveratrol in radiation-induced intestinal injury and the underlying mechanism remain unclear. Here, a C57BL/6 mouse model of RE was established and an intestinal epithelial cell line was used to evaluate the protective effects of resveratrol against radiation-induced intestinal injury and the underlying mechanisms. Resveratrol improved radiation-induced oxidative stress and cell apoptosis via upregulating antioxidant enzymes and downregulating p53 acetylation. In vivo, resveratrol-treated mice exhibited longer survival; longer villi; more intestinal crypt cells; upregulated expression of Ki67, catalase, and superoxide dismutase 2; and fewer inflammatory proteins and apoptotic cells. These protective effects were suppressed by inhibition of SIRT1. These results demonstrate that resveratrol can reduce radiation-induced intestinal injury by inhibiting oxidative stress and apoptosis via the SIRT1/FOXO3a and PI3K/AKT pathways.

摘要

放射性肠炎(RE)是最常见的放疗并发症,缺乏有效的 RE 治疗方法。白藜芦醇对辐射损伤有有益的作用。然而,白藜芦醇在放射性肠损伤中的作用及其潜在机制尚不清楚。本研究建立了 C57BL/6 小鼠放射性肠炎模型,并利用肠上皮细胞系评估了白藜芦醇对放射性肠损伤的保护作用及其潜在机制。白藜芦醇通过上调抗氧化酶和下调 p53 乙酰化来改善辐射诱导的氧化应激和细胞凋亡。在体内,白藜芦醇治疗的小鼠生存期更长;绒毛更长;肠隐窝细胞更多;Ki67、过氧化氢酶和超氧化物歧化酶 2 的表达上调;炎症蛋白和凋亡细胞减少。SIRT1 的抑制抑制了这些保护作用。这些结果表明,白藜芦醇通过 SIRT1/FOXO3a 和 PI3K/AKT 通路抑制氧化应激和细胞凋亡,从而减轻辐射引起的肠道损伤。

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