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评价白藜芦醇通过 TLR4/NF-κB/TNF-α 信号通路对 LPS 引起的脓毒症的保护作用:实验研究。

Evaluation of the protective role of resveratrol against sepsis caused by LPS via TLR4/NF-κB/TNF-α signaling pathways: Experimental study.

机构信息

Department of Histology and Embryology, Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey.

Department of Anatomy, Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey.

出版信息

Cell Biochem Funct. 2023 Jun;41(4):423-433. doi: 10.1002/cbf.3790. Epub 2023 Mar 27.

DOI:10.1002/cbf.3790
PMID:36970761
Abstract

The development and progression of sepsis are multifactorial and influence the immunological, endocrine, and cardiovascular systems of the body. Our knowledge of the key mechanisms involved in the pathogenesis of sepsis has expanded exponentially, yet this still needs to be translated into effective targeted therapeutic regimes. In the present study, we aimed to determine whether resveratrol has positive effects in the experimental sepsis rat model. Twenty-eight male Spraque-Dawley rats were randomly divided into four groups (n = 7) as follows: control, lipopolysaccharide (LPS) (30 mg/kg dose), resveratrol, and LPS and resveratrol. After the experiment, liver and kidney tissues were collected for histopathological evaluation, blood serums were collected to measure malondialdehyde levels with enyzme-linked immunosorbent assay, and Toll-like receptor-4 (TLR4), tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB) immunoreactivity density was evaluated immunohistochemically. In addition, messenger RNA expression levels for TLR4, TNF-α, NF-κB, interleukin-1β, and interleukin 6 were measured. In addition, the damage observed in liver and kidney tissue was determined by AgNOR (argyrophilic nucleolar organizer regions) staining. LPS application caused severe tissue damage, oxidative stress, and increased the expressions of proinflammatory proteins and genes we evaluated, while resveratrol application eliminated these negativities. Resveratrol has been proven to suppress the TLR4/NF-κB/TNF-α pathway, a possible therapeutic signaling pathway that is important in initiating the inflammatory response in an animal model of sepsis.

摘要

脓毒症的发生发展是多因素的,影响着机体的免疫、内分泌和心血管系统。我们对脓毒症发病机制中涉及的关键机制的认识已经呈指数级增长,但这仍需要转化为有效的靶向治疗方案。在本研究中,我们旨在确定白藜芦醇对实验性脓毒症大鼠模型是否有积极影响。28 只雄性 Spraque-Dawley 大鼠被随机分为四组(n=7):对照组、脂多糖(LPS)(30mg/kg 剂量)组、白藜芦醇组和 LPS 和白藜芦醇组。实验结束后,采集肝、肾组织进行组织病理学评估,采集血血清,用酶联免疫吸附法测量丙二醛水平,并通过免疫组织化学评估 Toll 样受体 4(TLR4)、肿瘤坏死因子-α(TNF-α)、核因子-κB(NF-κB)免疫反应密度。此外,还测量了 TLR4、TNF-α、NF-κB、白细胞介素 1β 和白细胞介素 6 的信使 RNA 表达水平。此外,还通过 AgNOR(嗜银核仁组织者区域)染色确定肝、肾组织的损伤情况。LPS 应用导致严重的组织损伤、氧化应激,并增加了我们评估的促炎蛋白和基因的表达,而白藜芦醇的应用消除了这些负面影响。白藜芦醇已被证明可抑制 TLR4/NF-κB/TNF-α 通路,这是一种可能的治疗信号通路,在脓毒症动物模型中对启动炎症反应很重要。

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