Effects of salvianolic acid A and salvianolic acid B in renal interstitial fibrosis via PDGF-C/PDGFR-α signaling pathway.
Effects of salvianolic acid A and salvianolic acid B in renal interstitial fibrosis via PDGF-C/PDGFR-α signaling pathway.
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丹酚酸 A 和丹酚酸 B 通过 PDGF-C/PDGFR-α 信号通路对肾间质纤维化的影响。
DOI：
10.1016/j.phymed.2022.154414
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发表时间：
2022-08
期刊：
影响因子：
7.9
通讯作者：
Jun Li
中科院分区：
文献类型：
--
作者：
Lan Yao;Renjie Zhao;Shiyang He;Qi Feng;Yingjin Qiao;Pei Wang;Jun Li
肾间质纤维化（renal interstitial fibrosis，RIF）是各种慢性肾脏病（chronic kidney diseases，CKD）所致终末期肾病（end-stage renal disease，ESRD）的主要病理特征，与肾功能损害及患者预后密切相关。从中药丹参中分离得到的丹参素A（SalA）和丹参素B（SalB）已被证实具有抗肝、心、肾纤维化作用。然而，Sal A和Sal B对RIF肾保护作用的确切分子机制，以及两者在RIF中是否存在差异尚不清楚，本研究通过体内和体外实验，研究Sal A和Sal B在RIF中的药理作用，并探讨其作用机制。通过肾组织学、肾功能、尿蛋白NAG、尿β2微球蛋白等肾功能相关指标评价Sal B和Sal A+B。此外，还检测了RIF相关标志物，如CTCF和Par 3。体内实验结果表明，Sal A、Sal B和Sal A+B可部分改善肾功能不全，增加Par-3的表达，降低CTGF、PDGF-C和PDGFR-α的表达。Sal A、Sal B和Sal A+B可通过调节PDGF-C/PDGFR-α信号通路逆转HSA诱导的HK-2细胞凋亡和ERS，提示Sal A、Sal B和Sal A+B可作为改善RIF的潜在治疗药物。
Renal interstitial fibrosis (RIF) is the main pathological feature of end-stage renal disease (ESRD) caused by various chronic kidney diseases (CKD), and is closely related to renal dysfunction and patient prognosis. Salvianolic acid A (Sal A) and salvianolic acid B (Sal B), isolated from traditional Chinese medicine Salviae miltiorrhizae, have been confirmed to have anti-fibrotic effects on liver, cardiac and kidney. However, the precise molecular mechanism underlying the nephroprotective effects of Sal A and Sal B, and whether there is a difference between the two in RIF are still unclear.This study investigated the pharmacological effects of Sal A and Sal B in RIF and explore the underlying mechanisms by in vivo and in vitro experiments.The nephroprotective effects of Sal A, Sal B and Sal A+B were evaluated by assessing the parameters related to kidney function such as renal histology, renal function, urinary protein NAG, urinary β2 microglobulin. In addition, RIF-related markers such as CTCF and Par3 were also detected. Thereafter, the related protein or gene levels of PDGF-C/PDGFR-α signaling pathways, apoptosis and endoplasmic reticulum stress (ERS) were determined by western blot, real-time PCR, flow cytometry or immunofluorescence staining.In vivo, the results showed that Sal A, Sal B and Sal A+B partially improved kidney dysfunction, increased the expression of Par-3 and reduced the expression of CTGF, PDGF-C and PDGFR-α. In vitro, the results also showed that Sal A, Sal B and Sal A+B reversed apoptosis and ERS in HSA-induced HK-2 cells via regulating PDGF-C/PDGFR-α signaling pathway.This article revealed a novel mechanism linking PDGF-C/PDGFR-α signaling pathway to RIF and suggested that Sal A, Sal B and Sal A+B were considered as potential therapeutic agents for the amelioration of RIF.
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影响因子：
7.5
作者：
Zhang N;Lo CW;Utsunomiya T;Maruyama M;Huang E;Rhee C;Gao Q;Yao Z;Goodman SB
通讯作者：
Goodman SB
影响因子：
21.3
作者：
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通讯作者：
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DOI：
10.1002/9781119413172.ch6
发表时间：
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期刊：
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影响因子：
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DOI：
10.19540/j.cnki.cjcmm.20200405.403
发表时间：
2020
期刊：
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
影响因子：
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作者：
["Lan Sun
通讯作者：
["Lan Sun
影响因子：
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作者：
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