Tanshinone IIA Alleviates Mitochondrial Dysfunction in Lipopolysaccharide-Induced Acute Kidney Injury in Mice by Activating SIRT1/PINK1-Mediated Mitophagy

Abstract

Background: Acute kidney injury (AKI) is a critical clinical condition closely associated with mitochondrial dysfunction. Tanshinone IIA has been shown to exert protective effects against AKI; however, the underlying mechanisms remain unclear. Objectives: This study aimed to investigate whether Tanshinone IIA mitigates lipopolysaccharide (LPS)-induced AKI through SIRT1/PINK1-mediated mitophagy. Methods: A mouse model of AKI was established by intraperitoneal injection of LPS. Renal function was assessed by measuring serum creatinine (Scr) and blood urea nitrogen (BUN) levels. Renal histopathological changes were evaluated using hematoxylin and eosin (HE) staining. Mitochondrial function was assessed by measuring adenosine triphosphate (ATP) content, mitochondrial reactive oxygen species (ROS), and mitochondrial membrane potential in renal tissue. The expression of mitophagy-related markers was analyzed by Western blotting. Results: Lipopolysaccharide treatment significantly increased Scr and BUN levels and induced marked renal pathological injury in mice compared with those in the control group. Tanshinone IIA intervention reduced Scr and BUN levels and alleviated renal tissue damage. Mitochondrial function analysis showed that Tanshinone IIA restored the LPS-induced reduction in ATP content, suppressed excessive mitochondrial ROS generation, and stabilized the mitochondrial membrane potential. Mechanistic analyses further demonstrated that Tanshinone IIA upregulated the LPS-induced expression of SIRT1 and PINK1, increased the LC3-II/LC3-I ratio, and promoted p62 degradation. Conclusions: Tanshinone IIA protects against LPS-induced AKI by improving mitochondrial function through the activation of SIRT1/PINK1-mediated mitophagy.