丹参多酚酸盐通过Keap1/Nrf2/ARE通路改善肾缺血再灌注损伤的机制研究

Abstract

Ethnopharmacological relevance Acute kidney injury (AKI) is a common clinical disease characterized by rapid loss of renal function. Salvianolate is a prescribed Chinese medicine derived from traditional Chinese medicine Salvia miltiorrhiza bunge that possesses many pharmacological effects, the active components extracted from Salvia miltiorrhiza bunge have been proved to protect ischemia-reperfusion (I/R)-AKI. Aim of the study This study aims to validate the therapeutic effect of SAL on I/R-AKI, and explore its potential pharmacological mechanism. Materials and methods Mice were pretreated with/without salvianolate (10, 30, and 90 mg/kg) before renal ischemia-reperfusion operation. Serum creatinine, BUN, and H&E staining were performed to evaluate renal function. Immunofluorescence analysis was conducted to measure renal tubular injury including inflammatory factors and peroxide level. Apoptosis of the kidney tissues was determined by TUNEL assay. Keap1-Nrf2-ARE and apoptosis signaling pathways were measured by Western blot , RT-PCR, and YO-PRO-1 staining in kidneys or NRK52E cells. Results Pretreatment with SAL effectively alleviated renal function and ameliorated epithelial tubular injury, oxidative stress, and inflammatory response. Furthermore, the mechanistic study demonstrated that the SAL exerts anti-apoptotic effects through activation of the Keap1-Nrf2-ARE signaling pathway in renal tubular cells. Conclusion These findings indicate the therapeutic benefit of salvianolate in the protection of renal injury from ischemia-reperfusion, and strengthen the evidence for the AKI treatment strategy by the anti-oxidative stress response, suggesting that SAL may be a potential agent for the treatment of AKI.