Intervention effect and mechanism of L-carnitine on acute kidney injury in septic mice

ZHANG Xing; ZHANG Lingge; ZHAO Tiantian; CHEN Zhuoxian; ZHAO Chengqun

doi:10.3969/j.issn.1002-266X.2024.32.009

Abstract：Objective To observe the intervention of L-carnitine on acute kidney injury induced by lipopolysaccha-ride(LPS)in septic mice and to explore its mechanism.Methods Thirty male SPF-grade C57BL/6 mice were randomly divided into three groups:the control group,model group,and L-carnitine group,with 10 mice in each group.Mice in the model group and L-carnitine group received intraperitoneal injection of LPS to establish the acute kidney injury models in-duced by sepsis,while mice in the L-carnitine group were pretreated with L-carnitine before LPS administration.Mice in the control group were intraperitoneally injected with normal saline.Mice were euthanized seven days after modeling to measure serum kidney function indicators,including creatinine(Scr),blood urea nitrogen(BUN),kidney injury mole-cule-1(KIM-1),and neutrophil gelatinase-associated lipocalin(NGAL).HE staining was performed to observe renal tis-sue pathological damage.Serum inflammatory factors,such as tumor necrosis factor-α(TNF-α),interleukin(IL)-8,and IL-6,were detected.Additionally,lipid metabolism indicators,including ATP,triglycerides,and lipids in renal tissues were measured,as well as the expression of carnitine palmitoyltransferase 1(CPT1)protein in kidney tissues.Human proximal tubular epithelial cell line HK-2 cells were divided into the Control,pSilencer3.1,and siCPT1 groups.Cells in the pSilencer3.1 and siCPT1 groups were transfected with the corresponding plasmids pSilencer3.1 and siCPT1,respec-tively;while cells in the Control group were not transfected.ATP and triglyceride levels in cells were measured at 48 h af-ter transfection.HK-2 cells were divided into the control,model,and L-carnitine groups.Cells in the model and L-carni-tine groups were stimulated with LPS for 12 h to simulate an in vitro sepsis model,with the L-carnitine group receiving L-carnitine pretreatment for one hour prior to LPS treatment.Cells in the Control group underwent no special treatment.The expression of CPT1 protein,ATP,and triglyceride levels in the cells were measured.Results Compared with the con-trol group,the model group exhibited increased serum kidney injury markers,levels of inflammatory factors,positive Oil Red O staining rates,and triglyceride content,and decreased ATP levels and CPT1 protein expression(all P<0.05).Compared with the model group,the L-carnitine group showed decreased levels of serum kidney injury markers,inflamma-tory factors,positive Oil Red O staining rates,and triglyceride content,as well as increased ATP levels and CPT1 protein expression(all P<0.05),with alleviated renal pathological changes.The siCPT1 group had lower ATP content and higher triglyceride content than the Control and pSilencer groups(all P<0.05).The expression of CPT1 protein and ATP content were lower,while triglyceride content was higher in the model group than in the Control group;conversely,the L-carnitine group had higher CPT1 protein expression and ATP content,and lower triglyceride content as compared with the model group(all P<0.05).Conclusions L-carnitine intervention can mitigate acute kidney injury in LPS-induced septic mice and reduce renal tissue inflammation.The mechanism may be related to the up-regulation of CPT1 protein expression and regulation of renal fatty acid metabolism.