Tanshinone I Regulates TGF-β1/Smad3 Signaling Pathway in Mitigating Sepsis-related Acute Kidney Injury in Rats

Abstract

Objective To investigate the effect of Ⅰ(Tanshinone Ⅰ (Tan Ⅰ) on the regulation of Wnt/β-catenin signaling pathway in rats with sepsis-associated acute kidney injury (SA-AKI). Methods The SA-AKI model rats were induced by cecal ligation and puncture (CLP), and Tan Ⅰ, TGF-β1 inhibitor salinomycin sodium and activator Laduviglusib were injected into rats by intraperitoneal injection. The pathological damage of rat kidney was observed by hematoxylin-eosin and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Serum concentrations of NGAL, IL-1β, IL-8, IL-6, and TNF-α were detected by ELISA, and serum concentrations of Cre and BUN were detected by creatinine (Cre) and blood urea nitrogen (BUN) kits. The expression of TGF-β1/Smad2/MMPs was detected by reverse transcription quantitative real-time polymerase chain reaction. Results Tan Ⅰ could reduce the renal damage induced by SA-AKI in rats, decrease the apoptosis, inhibit the expressions of inflammatory cytokines and SA-AKI markers NGAL, Cre and BUN, and inhibit the expression of TGF-β1/Smad2/MMPs. Salinomycin sodium reduced CLP-induced rat kidney injury and the production of inflammatory cytokines, and Laduviglusib further aggravated CLP-induced rat kidney injury. Tan Ⅰ could reverse the promotion effect of Laduviglusib on renal injury in SA-AKI rats. Conclusion Tan Ⅰ has a protective effect on CLP-induced SA-AKI in rats by inhibiting TGF-β1/Smad3 signaling pathway.