Efficacy ofα-Lipoic Acid Treatment on Sepsis-induced Acute Kidney Injury in Rats and Its Mechanisms / 中国医科大学学报

ABSTRACT

Objective To investigate the impact ofα?lipoic acid(ALA)treatment on sepsis?induced acute kidney injury in rats and explore the mechanisms. Methods A total of 32 male SD rats were randomized into 4 groupsnormal control group(group A),ALA?treated control group (group B),sepsis group(group C)and sepsis with ALA treated group(group D). Group A and B underwent sham operation,while CLP operations were conducted in group C and D. Rats in both group B and group D were then administered with 200 mg/kg ALA by oral gavage immediately after the surgical procedure. Twenty?four hours after the surgical procedure blood samples were obtained for the evaluation of creatinine,BUN,TNF?α,IL?6 and IL?1β. Rat kidneys were rapidly removed for PAS stain. Western blot was employed to determine the expression of NF?κB. Results Pathologi?cal changes of kidney were induced by sepsis and the level of creatinine,BUN,TNF?α,IL?6 and IL?1βwere significantly increased by 178%,66%, 55%,114%and 110%(P<0.01). respectively;simultaneously the phosphorylation and nuclear expression of NF?κB p65 in kidney tissues were significantly increased by 144%and 102%(P<0.01). Sepsis?induced acute kidney injury also significantly reduced the expression of IκBαby 61%(P<0.01). These changes were significantly suppressed by early ALA treatment. Compared with C group,the level of creatinine,BUN,TNF?α,IL?6 and IL?1βwere significantly decreased by 48%,26%,25%,37%and 40%(P<0.05),respectively,and the relative expression of IκBαwas increased by 103%(P<0.05). Conclusion The present study demonstrated that ALA can suppress the activation of NF?κB,thus ameliorat?ing sepsis?related acute kidney injury.