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表没食子儿茶素-3-没食子酸酯减轻小鼠单侧输尿管梗阻诱导的肾间质纤维化。

Epigallocatechin-3-gallate attenuates unilateral ureteral obstruction-induced renal interstitial fibrosis in mice.

作者信息

Wang Yanqiu, Wang Bowen, Du Feng, Su Xuesong, Sun Guangping, Zhou Guangyu, Bian Xiaohui, Liu Na

机构信息

Department of Nephrology, Shengjing Hospital of China Medical University, People's Republic of China (YW, FD, XS, GS, GZ, XB)

Department of Laboratory Medicine, Shengjing Hospital of China Medical University, People's Republic of China(BW)

出版信息

J Histochem Cytochem. 2015 Apr;63(4):270-9. doi: 10.1369/0022155414568019. Epub 2014 Dec 30.

Abstract

The severity of tubulointerstitial fibrosis is regarded as an important determinant of renal prognosis. Therapeutic strategies targeting tubulointerstitial fibrosis have been considered to have potential in the treatment of chronic kidney disease. This study aims to evaluate the protective effects of (-)-epigallocatechin-3-gallate (EGCG), a green tea polyphenol, against renal interstitial fibrosis in mice. EGCG was administrated intraperitoneally for 14 days in a mouse model of unilateral ureteral obstruction (UUO). The results of our histological examination showed that EGCG alleviated glomerular and tubular injury and attenuated renal interstitial fibrosis in UUO mice. Furthermore, the inflammatory responses induced by UUO were inhibited, as represented by decreased macrophage infiltration and inflammatory cytokine production. Additionally, the expression of type I and III collagen in the kidney were reduced by EGCG, which indicated an inhibition of extracellular matrix accumulation. EGCG also caused an up-regulation in α-smooth muscle actin expression and a down-regulation in E-cadherin expression, indicating the inhibition of epithelial-to-mesenchymal transition. These changes were found to be in parallel with the decreased level of TGF-β1 and phosphorylated Smad. In conclusion, the present study demonstrates that EGCG could attenuate renal interstitial fibrosis in UUO mice, and this renoprotective effect might be associated with its effects of inflammatory responses alleviation and TGF-β/Smad signaling pathway inhibition.

摘要

肾小管间质纤维化的严重程度被视为肾脏预后的重要决定因素。针对肾小管间质纤维化的治疗策略被认为在慢性肾脏病治疗中具有潜力。本研究旨在评估绿茶多酚(-)-表没食子儿茶素-3-没食子酸酯(EGCG)对小鼠肾间质纤维化的保护作用。在单侧输尿管梗阻(UUO)小鼠模型中,EGCG腹腔注射给药14天。组织学检查结果显示,EGCG减轻了UUO小鼠的肾小球和肾小管损伤,并减轻了肾间质纤维化。此外,UUO诱导的炎症反应受到抑制,表现为巨噬细胞浸润减少和炎症细胞因子产生减少。此外,EGCG降低了肾脏中I型和III型胶原蛋白的表达,这表明细胞外基质积累受到抑制。EGCG还导致α-平滑肌肌动蛋白表达上调和E-钙黏蛋白表达下调,表明上皮-间质转化受到抑制。这些变化与TGF-β1和磷酸化Smad水平降低平行。总之,本研究表明,EGCG可减轻UUO小鼠的肾间质纤维化,这种肾脏保护作用可能与其减轻炎症反应和抑制TGF-β/Smad信号通路的作用有关。

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