丹酚酸 C 抑制上皮-间充质转化并改善肾间质纤维化。

Salvianolic Acid C Inhibits the Epithelial-Mesenchymal Transition and Ameliorates Renal Tubulointerstitial Fibrosis.

机构信息

Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China.

TCM Institute of Kidney Disease of Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China.

出版信息

Front Biosci (Landmark Ed). 2023 Jun 27;28(6):121. doi: 10.31083/j.fbl2806121.

DOI:10.31083/j.fbl2806121

PMID:37395021

Abstract

BACKGROUND

Salvianolic acid C (SAC) is a natural compound derived from that can protect against renal diseases. The aims of this work were to explore the effect of SAC on kidney tubulointerstitial fibrosis and study the associated mechanism.

METHODS

Models for unilateral ureteral obstruction (UUO) and aristolochic acid I (AAI) were established in mice to study renal tubulointerstitial fibrosis. Rat kidney fibroblasts (NRK-49F) and human kidney epithelial cells (HK2) were used as cellular models to evaluate the effects of SAC on kidney fibrosis.

RESULTS

Treatment with SAC for two weeks reduced the level of renal tubulointerstitial fibrosis in UUO- and AAI-induced fibrotic kidneys, as demonstrated by Masson's staining and Western blot. SAC inhibited extracellular matrix protein expression in NRK-49F cells and TGF-β-stimulated HK2 cells in dose-dependent fashion. Moreover, SAC inhibited the expression of epithelial-mesenchymal transition (EMT) factors in animal and cellular models of kidney fibrosis, as well as the EMT-related transcription factor snail. Furthermore, SAC inhibited the fibrosis-related signaling pathway Smad3 in the fibrotic kidneys of two mouse models and in renal cells.

CONCLUSIONS

We conclude that SAC inhibits EMT and ameliorates tubulointerstitial fibrosis through involvement of the signaling pathway for transforming growth factor-β (TGF-β)/Smad.

摘要

背景

丹酚酸 C（SAC）是一种天然化合物，可从丹参中提取，具有防治肾脏疾病的作用。本研究旨在探讨 SAC 对肾间质纤维化的作用，并探讨其相关机制。

方法

通过单侧输尿管梗阻（UUO）和马兜铃酸 I（AAI）模型建立，在小鼠中研究 SAC 对肾间质纤维化的影响。采用大鼠肾成纤维细胞（NRK-49F）和人肾上皮细胞（HK2）作为细胞模型，评估 SAC 对肾纤维化的作用。

结果

SAC 治疗 2 周可减轻 UUO 和 AAI 诱导的纤维化肾脏中的肾小管间质纤维化程度，通过 Masson 染色和 Western blot 验证。SAC 呈剂量依赖性抑制 NRK-49F 细胞和 TGF-β刺激的 HK2 细胞中细胞外基质蛋白的表达。此外，SAC 在两种肾纤维化动物模型和肾细胞中抑制 EMT 因子和 EMT 相关转录因子 snail 的表达。而且，SAC 抑制了两种小鼠模型纤维化肾脏和肾细胞中纤维化相关信号通路 Smad3。