感染、炎症、修复2025,Vol.26Issue(2):92-97,6.DOI:10.3969/j.issn.1672-8521.2025.02.004
葡萄糖酸内酯对脓毒症急性肾损伤的作用及机制研究
Effect and mechanism of glucono delta-lactone on acute kidney injury in sepsis
摘要
Abstract
Objective:To investigate the effect and potential mechanism of glucono delta-lactone(GDL)on acute kidney injury in sepsis.Methods:Thirty-two clean grade C57BL/6J male rats were randomly divided into four groups(n=8):(1)Normal control group:intraperitoneal injection of normal saline;(2)Single drug group(GDL group):intraperitoneal injection of GDL;(3)Model group:intraperitoneal injection of lipopolysaccharide(LPS);(4)GDL treatment group(LPS+GDL group):intraperitoneal injection of LPS and GDL.These rats were killed 24 hours later,and the kidney tissue and serum were kept sterile.The mRNA expression of inflammatory factors in kidney tissue was detected by reverse transcription-polymerase chain reaction(RT-PCR).Rats kidney tissue was sliced and the degree of kidney injury was observed under microscope.The levels of malondialdehyde(MDA),superoxide dismutase(SOD)and nitric oxide(NO)in kidney tissue and serum creatinine and urea nitrogen were detected by corresponding kits.The expression levels of apoptosis-related protein,Bax,B-cell lymphoma-2(Bcl-2),cleaved-caspase-3,nuclear factor-κB(NF-κB),JAK2/STAT3 pathway related proteins and inducible nitric oxide synthase(iNOS)in kidney tissues were detected by Western blot and immunohistochemistry.Results:There were no significant differences between GDL group and normal control group(P>0.05).Compared with normal control group,serum creatinine and urea nitrogen levels and mRNA levels of TNF-α,IL-6 and IL-1β in kidney tissue were significantly increased in model group(P<0.05),while kidney cell degeneration and necrosis,interstitial edema with inflammatory cell infiltration were significantly increased in model group(P<0.05).After GDL intervention,the above indexes were significantly reduced compared with the model group(P<0.05),and the kidney tissue cell injury was significantly reduced compared with the model group(P<0.05).Compared with normal control group,the ratio of Bax/Bcl-2,mRNA and protein expression of cleaved-caspase-3,MDA,NO and iNOS,and the phosphorylation levels of p65,JAK2 and STAT3 in kidney tissue of model group were significantly increased(P<0.05),and the SOD level was significantly decreased(P<0.05).Compared with the model group,the ratio of Bax/Bcl-2,mRNA and protein expression of cleaved-caspase-3,MDA,NO and iNOS,and the phosphorylation levels of p65,JAK2 and STAT3 in kidney tissue of rats in LPS+GDL group were significantly decreased(P<0.05),and the level of SOD was significantly increased(P<0.05).Conclusions:By inhibiting the activation of NF-κB,JAK2/STAT3 pathway,iNOS expression and NO production,GDL can reduce oxidative stress and alleviate kidney injury in sepsis.关键词
葡萄糖酸内酯/脓毒症/肾损伤,急性/氧化应激/核因子-κB/JAK2/STAT3/信号通路Key words
Glucono delta-lactone/Sepsis/Acute kidney injury/Oxidative stress/Nuclear factor-κB/JAK2/STAT3/Signal pathway分类
医药卫生引用本文复制引用
郑伟洁,胡系意,陈隆望,吴斌,卢中秋,连洁..葡萄糖酸内酯对脓毒症急性肾损伤的作用及机制研究[J].感染、炎症、修复,2025,26(2):92-97,6.基金项目
浙江省温州市科技计划项目(Y20220090) (Y20220090)