Effect of L-carnitine on renal ischemia-reperfusion injury / 中华器官移植杂志

ABSTRACT

Objective To investigate the effect of L-camitine on renal ischemia-reperfusion (IR) injury (IRI) and Nrf2-ARE signaling pathway in rats.Methods Rats were randomly separated into the following experimental groupscontrol group (group C),IRI group (group I) and L-carnitine group (group L).Rats accepted no treatment of ischemic reperfusion in group C.In groups I and group L,the renal IRI model was established.L-carnitine was injected through the tail vein in group L,while the equal volume of saline was injected in group C and group I.Rats were killed at 3,6,and 24 h after IR.The levels of serum creatinine (Cr) and blood urea nitrogen (BUN),the activity of superoxide dismutase (SOD) and the content of malonaldehyde (MDA) in serum were measured.The histopathological lesions were observed in renal tissues after 24-h IR.RT-PCR was used to detect the levels of Nrf2,HO-1 and γ-GCS mRNA.Western blotting and immunohistochemistry were used to detect the levels and localization of Nrf2 protein in renal tissues after 6-h IR.Results The levels of Cr and BUN in group I and group L were higher than those in group C at 3 h after IR.At 6 h after IR,the levels of Cr and BUN in group L were lower than those in group I (P＜0.01 ).At 24 h after IR,the levels of Cr and BUN in group L were still lower than those in group I though both of them were reduced (P＜0.05).At all time points,the activity of SOD in group L was higher and the content of MDA was lower than those in group I (P＜ 0.05). As compared with group I,the renal histopathological lesions were alleviated in group L at 24 h after IR.At 6 h after IR,levels of Nrf2,HO-1,γ-GCS mRNA and Nrf2 protein in group I were increased as compared with group C,but decreased as compared with group L.Beyond that,the expression of nuclear Nrf2 protein in group L was higher than that in group I.Conclusion L-carnitine can protects the kidney against IRI significantly,which may be due to the up-regulated expression of antioxidant genes by activating the Nrf2-ARE signaling pathway.