甘氨熊去氧胆酸减轻脓毒症相关急性肾损伤作用的研究OA

Objective:To identify potential key metabolites alleviating sepsis-associated acute kidney injury(SA-AKI)based on metabolomics,and to investigate the renal protective effect of glycoursodeoxycholic acid(GUDCA).Methods:From July 2024 to February 2025,60 sepsis patients admitted to the intensive care unit(ICU)of Bobai County People's Hospital in Guangxi were selected and divided into AKI group(n=30)and con-trol group(n=30)based on the presence or absence of acute kidney injury(AKI).Spearman correlation analysis was used to explore the correlation of bile acid metabolites with kidney function and prognosis-related indicators.Male C57BL/6 mice were divided into control group,GUDCA group,lipopolysaccharide(LPS)group and GUDCA+LPS group.A mouse model of SA-AKI was established via intraperitoneal injection of LPS.Plasma urea nitrogen levels were detected using the diacetyl-monoxime colorimetric method.Plasma creatinine levels were measured using the creatine oxidase method.Plasma levels of inflammatory factors interleukin-1β(IL-1β),IL-6 and tumor necrosis factor-α(TNF-α)were measured using enzyme-linked immunosorbent assay(ELISA).Hematoxylin-eosin(HE)staining was used to observe pathological changes in kidney tissues.Immunofluores-cence staining was used to detect the expressions of kidney injury markers neutrophil gelatinase-associated lipo-calin(NGAL)and kidney injury molecule-1(KIM-1),and quantitative real-time polymerase chain reaction(RT-qPCR)was used to detect the expressions of oxidative stress-related genes in kidney tissues.An LPS-induced hu-man renal tubular epithelial cell injury model was established,and the levels of reactive oxygen species(ROS)and the expressions of inflammatory factors were detected after the intervention with GUDCA.Results:GUDCA was negatively correlated with plasma creatinine level and positively correlated with glomerular filtration rate(GFR),24-hour urine output,and 28-day survival rate(P＜0.05).Compared with those in the control group,mice in the LPS group exhibited aggravated renal tubular pathological damage,increased fluorescence intensities of KIM-1 and NGAL,increased plasma creatinine,urea nitrogen,IL-1 β,IL-6 and TNF-α levels and relative expres-sions of NOX4 gene in kidney tissues,and decreased relative expressions of SOD2 and GPX1 genes(P＜0.05).Compared with those in the LPS group,mice in the GUDCA+LPS group showed alleviated renal tubular patho-logical damage,decreased fluorescence intensities of KIM-1 and NGAL,decreased plasma creatinine,urea nitro-gen,IL-1 β,IL-6 and TNF-α levels and relative expressions of NOX4 gene in kidney tissues,increased relative ex-pressions of SOD2 and GPX1 genes and increased expressions of NQO1,HO-1 and Nrf2(P＜0.05).Cell experi-ments demonstrated that compared with the control group,the LPS group exhibited increased levels of ROS and expressions of IL-1β、IL-6 and TNF-α in HK-2 cells(P＜0.05),whereas compared with the LPS group,the GUDCA+LPS group showed decreased levels of ROS and expressions of IL-1β、IL-6 and TNF-α in HK-2 cells af-ter the intervention with GUDCA(P＜0.01).Conclusion:GUDCA is correlated with the degree of renal function impairment and short-term prognosis in SA-AKI.It can alleviate renal tubular injury by inhibiting inflammatory response and oxidative stress,suggesting its potential as a biomarker for SA-AKI.