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葡萄籽多酚通过抑制炎症和细胞凋亡改善葡聚糖硫酸钠诱导的结肠炎。

Grape Seed Polyphenols Ameliorated Dextran Sulfate Sodium-Induced Colitis via Suppression of Inflammation and Apoptosis.

机构信息

Peking University Institute of Cardiovascular Sciences, Peking University Health Science Center, Peking University, Beijing, China.

Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, China.

出版信息

Pharmacology. 2020;105(1-2):9-18. doi: 10.1159/000501897. Epub 2019 Nov 19.

DOI:10.1159/000501897
PMID:31743904
Abstract

BACKGROUND

Ulcerative colitis (UC) is an inflammatory bowel disease. Its onset is typically gradual, usually followed by periods of spontaneous remission and subsequent relapses. Grape seed polyphenols (GSP), a natural product extracted from grape seeds, have strong anti-inflammatory functions.

OBJECTIVES

In this study, we investigated whether GSP has an inhibitory effect on UC and its related mechanism or not.

METHODS

We induced UC by 2.5% dextran sulfate sodium (DSS) and GSP at different doses (500 and 750 mg/kg body weight per day) was administrated to the mice by gavage. Body weight, diarrhea, and bloody stool were recorded every day to evaluate disease activity index. Hemotoxylin-eosin staining and immunohistochemical staining were used to identify the histological damages and inflammatory infiltration in colon tissues. Real-time polymerase chain reaction was used to evaluate mRNA expression of interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α and the expression of phosphorylated-signal transducer and activator of transcription 3 (STAT3) and STAT3 were assessed by western blot. The immunofluorescent assay was used to evaluate the apoptosis of intestinal epithelial cells (IECs).

RESULTS

GSP could alleviate the loss of body weight, diarrhea, bloody stool, the mucosal damage, and inflammatory infiltration. GSP could also downregulate the mRNA expression of inflammatory cytokines IL-6, IL-1β, and TNF-α as well as the phosphorylation of STAT3 and ameliorate the apoptosis of IECs.

CONCLUSIONS

Our study suggests that GSP has protective effects against DSS-induced UC, which may through suppression of inflammation and apoptosis.

摘要

背景

溃疡性结肠炎(UC)是一种炎症性肠病。其发病通常是逐渐的,通常在自发缓解期和随后的复发期之间交替。葡萄籽多酚(GSP)是一种从葡萄籽中提取的天然产物,具有很强的抗炎功能。

目的

本研究旨在探讨 GSP 是否对 UC 具有抑制作用及其相关机制。

方法

我们通过给予 2.5%葡聚糖硫酸钠(DSS)诱导 UC,并用不同剂量(500 和 750 mg/kg 体重/天)的 GSP 通过灌胃给予小鼠。每天记录体重、腹泻和血便,以评估疾病活动指数。苏木精-伊红染色和免疫组织化学染色用于鉴定结肠组织的组织学损伤和炎症浸润。实时聚合酶链反应用于评估白细胞介素(IL)-6、IL-1β 和肿瘤坏死因子(TNF)-α 的 mRNA 表达,并用 Western blot 评估磷酸化信号转导和转录激活因子 3(STAT3)和 STAT3 的表达。免疫荧光法用于评估肠上皮细胞(IEC)的凋亡。

结果

GSP 可减轻体重减轻、腹泻、血便、黏膜损伤和炎症浸润。GSP 还可以下调炎症细胞因子 IL-6、IL-1β 和 TNF-α 的 mRNA 表达以及 STAT3 的磷酸化,并改善 IEC 的凋亡。

结论

我们的研究表明,GSP 对 DSS 诱导的 UC 具有保护作用,可能通过抑制炎症和凋亡来实现。

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