Blood Purification Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Research Institute of Nephrology, Zhengzhou University, Zhengzhou 450052, China; Basic and Applied Laboratory of Traditional Chinese Medicine, the Fifth Affiliated Hospital of Zunyi Medical University, Zhuhai 519000, China; Key Laboratory of Pharmacology, Zunyi Medical University, Zunyi 563000, China.
Basic and Applied Laboratory of Traditional Chinese Medicine, the Fifth Affiliated Hospital of Zunyi Medical University, Zhuhai 519000, China; Key Laboratory of Pharmacology, Zunyi Medical University, Zunyi 563000, China; Department of Nephrology, the Affiliated Hospital of Chengdu University, Chengdu 610081, China.
Phytomedicine. 2022 Nov;106:154414. doi: 10.1016/j.phymed.2022.154414. Epub 2022 Aug 27.
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.
肾间质纤维化（RIF）是各种慢性肾脏病（CKD）引起的终末期肾病（ESRD）的主要病理特征，与肾功能障碍和患者预后密切相关。丹参中的丹酚酸 A（Sal A）和丹酚酸 B（Sal B）已被证实对肝、心和肾具有抗纤维化作用。然而，Sal A 和 Sal B 的肾保护作用的确切分子机制，以及它们在 RIF 中的作用是否存在差异尚不清楚。
本研究通过体内和体外实验探讨 Sal A 和 Sal B 对 RIF 的药理作用及其潜在机制。
通过评估与肾功能相关的参数，如肾组织学、肾功能、尿蛋白 NAG、尿β2 微球蛋白，评价 Sal A、Sal B 和 Sal A+B 的肾保护作用。此外，还检测了 RIF 相关标志物 CTCF 和 Par3。然后，通过 Western blot、实时 PCR、流式细胞术或免疫荧光染色测定 PDGF-C/PDGFR-α 信号通路、细胞凋亡和内质网应激（ERS）相关蛋白或基因水平。
体内实验结果表明，Sal A、Sal B 和 Sal A+B 部分改善了肾功能，增加了 Par-3 的表达，降低了 CTGF、PDGF-C 和 PDGFR-α 的表达。体外实验结果也表明，Sal A、Sal B 和 Sal A+B 通过调节 PDGF-C/PDGFR-α 信号通路逆转了 HSA 诱导的 HK-2 细胞中的细胞凋亡和 ERS。
本文揭示了 PDGF-C/PDGFR-α 信号通路与 RIF 之间的新机制，并表明 Sal A、Sal B 和 Sal A+B 可被视为改善 RIF 的潜在治疗剂。
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