| Objective:Constructing the model of rat renal ischemic reperfusion injury (IRI) to investigate the protective effect of L-carnitine on renal IRI. Detecting the expression of Nrf2and the mRNA of downstream antioxidant genes to explore the mechanism of L-carnitine. Trying to provide new method for the treatment of renal IRI.Methods:Rats were randomly separated into the following experimental groups:control group(group C), IRI group(group I) and L-carnitine group(group L), within each group, rats were further divided into three subgroups:3h,6h,24h IR treatment. Rats accepted no treatment of ischemic reperfusion in group C. In group I and group L, the renal IRI model was established. L-carnitine was injected through tail vein in group L while the equal volume of saline was injected in group C and group I. The levels of serum creatinine(Cr) and urea nitrogen(BUN), the activities of superoxide dismutase(SOD) and the content of malonaldehyde(MDA) in serum were measured. The histopathological lesions were observed in renal tissues for24h IR treatment. RT-PCR was used to detect the levels of Nrf2, HO-1and y-GCS mRNA; Western-blot and immunohistochemistry were used to detect the levels and localization of Nrf2protein in renal tissues for6h IR treatment.Results:(1) The levels of Cr and BUN In group I and group L was higher than those in group C3h after IR. At6h after IR, The levels of Cr and BUN in group L was lower than those in group I(P<0.01). At24h after IR, the levels of Cr and BUN in group L was still lower than those in group I though both of them had fallen(P<0.05).(2) 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). (3) As compared with group I, the renal histopathological lesions were improved in group L at24h after IR.(4) At6h after IR, levels of Nrf2, HO-1, y-GCS mRNA and Nrf2protein in group I were increased as compared with group C, but decreased as compared with group L. Beyond that, the expression of nuclear Nrf2protein in group L was higher than that in group I.Conclusions:(1) L-carnitine can ameliorate the renal dysfunction and pathological lesion in IRI.(2) L-carnitine can increase the activities of SOD and decrease the content of MDA, thus, it has obvious antioxidation in IRI.(3) Endogenous protective mechanism can be started by Oxidative stress through activating the Nrf2-ARE signaling pathway in ischemia-reperfusion.(4) L-carnitine can promote the nuclear translocation of Nrf2, and incress the expression of antioxidant genes through activating the Nrf2-ARE signaling pathway furtherly to protect renal against IRI. |
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