Archives of biochemistry and biophysics · 2026
Sodium lactate attenuates LPS-induced acute kidney injury by suppressing CHOP dependent endoplasmic reticulum stress.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Ma Xinyue, Zhang Haichao, Wang Yunlong, Sun Huiwen, Liang Jingjing, Wang Yuhang, Yang Wei
Аннотация
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, ER stress, dampening of inflammatory and apoptotic signaling, with concomitant effects on LDHA/PKM2. These findings support further evaluation of sodium lactate as a metabolism-informed intervention for sepsis-related AKI, including dose-response, time-course, and upstream UPR-branch analyses in extended preclinical studies.
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, ER stress, dampening of inflammatory and apoptotic signaling, with concomitant effects on LDHA/PKM2. These findings support further evaluation of sodium lactate as a metabolism-informed intervention for sepsis-related AKI, including dose-response, time-course, and upstream UPR-branch analyses in extended preclinical studies.