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鞣花酸通过阻断上皮-间质转化改善肾纤维化。

Ellagic acid ameliorates renal fibrogenesis by blocking epithelial-to-mesenchymal transition.

作者信息

Huang Po-Yu, Hsieh Yi-Hsien, Ting Yi-Hsuan, Lee Chu-Che, Tsai Jen-Pi

机构信息

Division of Nephrology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan.

School of Medicine, Tzu Chi University, Hualien, Taiwan.

出版信息

Tzu Chi Med J. 2023 Oct 24;36(1):59-66. doi: 10.4103/tcmj.tcmj_106_23. eCollection 2024 Jan-Mar.

Abstract

OBJECTIVES

Ellagic acid (EA), a kind of polyphenol found in numerous fruits and vegetables, has anti-inflammatory, anti-apoptotic, anti-oxidant, and anti-fibrotic effects against a variety of diseases, but its role in mediating renal fibrogenesis remains unknown.

MATERIALS AND METHODS

We used an mouse unilateral ureteral obstruction (UUO) model and an model with HK-2 cell lines treated with EA and transforming growth factor β1 (TGF-β1). The expression of epithelial-to-mesenchymal transition (EMT)-related proteins of UUO mice was examined using immunohistochemical staining. Liver function and renal function were evaluated using biochemical testing. Western blot analysis was used to determine the proteins related to EMT, and MTT assay was used to determine cell viability.

RESULTS

In UUO mice fed EA, both microscopical examination with immunohistochemical staining and western blotting protein analysis showed reduced expression of fibrotic (α-SMA, fibronectin, and collagen I)- and EMT (vimentin and N-cadherin)-related proteins, compared with sham control. In HK-2 cells treated with TGF-β1, EA decreased motility as well as expression of α-SMA, collagen-I, fibronectin, N-cadherin, and vimentin.

CONCLUSION

EA reduced the progression of the morphological transformations and concomitantly suppressed the expression of fibrotic- and EMT-related proteins and . These findings improved our understanding of the role of EA in suppressing renal fibrogenesis and demonstrated the promising role EA may play in the management of chronic kidney disease.

摘要

目的

鞣花酸(EA)是一种存在于多种水果和蔬菜中的多酚,对多种疾病具有抗炎、抗凋亡、抗氧化和抗纤维化作用,但其在介导肾纤维化发生中的作用尚不清楚。

材料与方法

我们使用小鼠单侧输尿管梗阻(UUO)模型以及用EA和转化生长因子β1(TGF-β1)处理HK-2细胞系的模型。采用免疫组织化学染色检测UUO小鼠上皮-间质转化(EMT)相关蛋白的表达。通过生化检测评估肝功能和肾功能。采用蛋白质印迹分析确定与EMT相关的蛋白,采用MTT法测定细胞活力。

结果

在喂食EA的UUO小鼠中,与假手术对照组相比,免疫组织化学染色显微镜检查和蛋白质印迹分析均显示纤维化(α-平滑肌肌动蛋白、纤连蛋白和I型胶原)和EMT(波形蛋白和N-钙黏蛋白)相关蛋白的表达降低。在用TGF-β1处理的HK-2细胞中,EA降低了细胞活力以及α-平滑肌肌动蛋白、I型胶原、纤连蛋白、N-钙黏蛋白和波形蛋白的表达。

结论

EA减少了形态学转变的进程,并同时抑制了纤维化和EMT相关蛋白的表达。这些发现增进了我们对EA在抑制肾纤维化发生中作用的理解,并证明了EA在慢性肾脏病管理中可能发挥的有前景的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9f4/10887343/aface1656268/TCMJ-36-59-g001.jpg

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