Artesunate Mitigates Sepsis-Induced Acute Kidney Injury via Lactate/AMPK/mTOR-Regulated Autophagy Based on Multi-Omics

作者：Hetao Chen, Peipei Du, Ran Guo, Xuejiao Li, Lei Zhang, Jiajia Duan, Menglu Chen, Jia Guo, Ying Li, Tao Jiang · 发表于：Drug Design Development and Therapy · 年份：2025 · DOI：10.2147/dddt.s525701 · 被引用次数：6 · 研究领域：Acute Kidney Injury Research、Dialysis and Renal Disease Management、Autophagy in Disease and Therapy

Background: Sepsis-induced acute kidney injury (S-AKI) is a form of acute renal failure resulting from a systemic inflammatory response triggered by infection, and has emerged as a significant public health challenge. Prior studies have demonstrated that artesunate (ART) exerts therapeutic effects on S-AKI by mitigating inflammation and oxidative stress. However, the precise regulatory mechanisms remain to be fully elucidated. Methods: This study investigates the impact of ART on renal function in a sepsis mouse model and its effect on LPS-induced cytotoxicity in HK-2 cells, aiming to clarify the potential therapeutic mechanisms underlying ART's efficacy in S-AKI. We evaluated changes in body weight, kidney index, biochemical markers, and histopathological alterations in mice, as well as proliferation and apoptosis in HK-2 cells. Additionally, metabolomics and transcriptomics were employed to identify key pathways involved in ART's therapeutic actions. Results: Our findings indicate that ART significantly improves renal function in sepsis mice, evidenced by increased body weight, reduced kidney index, and diminished pathological damage. Furthermore, ART alleviates LPS-induced cytotoxicity in HK-2 cells, reduce the levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α, and increase the levels of antioxidant GSH. Integrative analysis of metabolomics and transcriptomics reveals that ART intervention markedly decreases lactate levels, inhibits excessive AMPK activation, rel...