Tanshinone IIA prevents septicemia acute kidney injury via regulating the DUSP10/JNK/P38/NLRP3 pathway

OBJECTIVE: To investigate the protective effects and underlying mechanisms of tanshinone IIA in preventing septicemia acute kidney injury (SA-AKI). METHODS: Mice were pretreated with tanshinone IIA via intraperitoneal injection, followed by lipopolysaccharide (LPS) administration to induce SA-AKI. Hematoxylin-eosin (HE) staining was used to assess renal tissue injury to confirm successful model establishment. In vitro, HK2 cells were treated with LPS and/or tanshinone IIA. Differentially expressed genes (DEGs) between the LPS and tanshinone IIA + LPS groups were identified via high-throughput sequencing. qPCR was performed to validate mRNA expression of key DEGs. Protein expression in mouse kidney and HK2 cells was analyzed using immunohistochemistry and western blot. RESULTS: Mice in the SA-AKI model demonstrated severe renal damage, with elevated levels of serum creatinine and urea nitrogen, as well as increased apoptosis and glycogen accumulation. Tanshinone IIA pretreatment significantly alleviated these pathological changes. Flow cytometry confirmed that LPS induced HK2 cell apoptosis, which was attenuated by tanshinone IIA. Transcriptomic analysis revealed 121 upregulated and 65 downregulated genes. Western blot showed that LPS increased JNK, p38, NLRP3 and Caspase-1 expression, and decreased DUSP10 and ALDH2 expression, while tanshinone IIA pretreatment reversed these effects. Similarly, immunohistochemistry and western blot analyses demonstrated elevated contents of KIM-1, NLRP3, JNK and Caspase-1, and reduced DUSP10 and ALDH2 in SA-AKI mice. CONCLUSION: Tanshinone IIA exerts a protective effect against SA-AKI by mitigating inflammation and apoptosis. Mechanistically, these effects appear to be mediated through DUSP10 and modulation of the JNK/P38/NLRP3 pathway. These findings suggest that tanshinone IIA might be a potential therapeutic strategy for SA-AKI.