Sodium lactate attenuates LPS-induced acute kidney injury by suppressing CHOP dependent endoplasmic reticulum stress.

作者：Xinyue Ma, Haichao Zhang, Yunlong Wang, Huiwen Sun, Jingjing Liang, Yuhang Wang, Wei Yang · 发表于：Archives of Biochemistry and Biophysics · 年份：2026 · DOI：10.1016/j.abb.2026.110941 · 研究领域：Medicine

BACKGROUND Dysregulated lactate metabolism and endoplasmic reticulum (ER) stress contribute to sepsis-associated acute kidney injury (AKI). We tested whether sodium lactate mitigates LPS-induced AKI in association with reduced CHOP signaling. METHODS LPS-induced AKI was established in mice and modeled in HK-2 cells. NALA was administered in vivo and in vitro. Renal injury was assessed by histology and renal function (serum creatinine, blood urea nitrogen). Inflammatory and apoptotic signaling (IL-6, IL-1β, TNF-α; Bcl-2, Bax, cleaved caspase-3) and ER-stress markers (CHOP) were quantified by western blotting and RT-qPCR. The glycolytic enzymes LDHA and PKM2 were measured to explore effects on lactate-related metabolism. Group comparisons used standard parametric/non-parametric tests and one-way ANOVA with multiple comparisons. RESULTS In mice, NALA attenuated tubular injury and lowered serum creatinine and urea nitrogen compared with LPS alone. Renal expression of IL-6, IL-1β and TNF-α decreased with NALA, accompanied by increased Bcl-2 and reduced Bax and cleaved caspase-3. NALA downregulated CHOP in renal tissue. In HK-2 cells, NALA similarly blunted LPS-induced inflammatory cytokines and apoptosis-related changes and reduced CHOP expression. Across models, NALA decreased LDHA and PKM2 expression, indicating modulation of glycolysis-linked lactate metabolism. CONCLUSIONS NALA mitigates LPS-induced AKI in vivo and in vitro, associated with suppression of CHOP expression...