| Objective: Constructing the model of rat liver warm ischemic reperfusion injury(WIRI),then to investigate the protective effect of L-carnitine on liver WIRI and to explore its possible mechanism for Nrf2/HO-1 pathway.Trying to prevent new method for the treatment of liver WIRI.Methods: Random number table method was used to divide seventy-two male SD rats into 3 groups: Sham-operated(SO),Liver warm ischemia and reperfusion(WIR),L-Carnitine pretreatment of WIR(LC).Within each group,rats were further divided into three subgroups:0h,6h and 12 h subgroups.Rats accepted no treatment of ischemic reperfusion in SO group.In WIR group and LC group,the liver WIRI model was established.L-Carnitine was injected through introperitoneal in LC group while the equal volume of saline was injected in SO group and WIR group.And then,the levels of serum Alanine aminotransferase(ALT)and Aspartate aminotransferase(AST)as well as the activities of Superoxide dismutase(SOD)and the content of Malondial-dehyde(MDA)in liver tissues were detected.Meanwhile,the histopathological change of liver tissues was observed as well as the mRNA expression of NF-E2-related fator 2(Nrf2)and heme oxygenase 1(HO-1)in liver tissues were detected by Real-time PCR.Results: 1.Compared with the SO group,serum ALT and AST level of 0h,6h and 12 h subgroups in the WIR group at the same time point were higher,difference was statisticallysignificant(P<0.05);And compared with the SO group,serum ALT and AST level of 0h,6h and 12 h subgroups in the LC group at the same time point were higher,difference was not statistically significant(P>0.05);Compared with the WIR group,serum ALT level of 0h,6h and 12 h subgroups in the LC group at the same time point were lower,among them 6h and12 h subgroups in the LC group,difference was statistically significant(P<0.05);And compared with the WIR group,serum AST level of 0h,6h and 12 h subgroups in the LC group at the same time point were lower,difference was statistically significant(P<0.05).2.Compared with the SO group,SOD activities of liver homogenate of 0h,6h and 12 h subgroups in the WIR group at the same time point were lower,difference was statistically significant(P<0.05);And compared with the SO group,SOD activities of liver homogenate of 0h,6h and 12 h subgroups in the LC group at the same time point were higher,difference was statistically significant(P<0.05).Compared with the SO group,the content of MDA of liver homogenate of 0h,6h and 12 h subgroups in the WIR group at the same time point were higher,difference was statistically significant(P<0.05);while compared with the SO group,the content of MDA of liver homogenate of 0h,6h and 12 h subgroups in the LC group,difference was not statistically significant(P>0.05).In addition,SOD activities of liver homogenate of 0h,6h and 12 h subgroups in the LC group at the same time point were higher than those of the WIR group,difference was statistically significant(P<0.05),while the content of MDA was lower,difference was statistically significant(P<0.05).3.Compared with the SO group,the mRNA expression of Nrf2 and HO-1 of 0h,6h and 12 h subgroups in the WIR group at the same time point,difference was statistically significant(P<0.05),among them the mRNA expression of Nrf2 and HO-1 of 0h subgroups in the WIR group was low expression;And compared with the SO group,the mRNA expression of Nrf2 and HO-1 of 6h and 12 h subgroups in the LC group at the same time point difference was statistically significant(P<0.05),while the m RNA expression of Nrf2 and HO-1 of 0h subgroups in the LC group,difference was not statistically significant(P>0.05).Compared with the WIR group,the mRNA expression of Nrf2 of 0h,6h subgroups in the LC group at the same time point,difference was statistically significant(P<0.05),while the mRNA expression of Nrf2 of 12 h subgroups in the LC group,difference was not statistically significant(P>0.05).And compared with the WIR group,the mRNA expression of HO-1 of 6h subgroups in the LC group at the same time point,difference was statistically significant(P<0.05),while the mRNA expression of HO-1 of 0h,12 h subgroups in the LC group,difference was not statistically significant(P>0.05).4.Histopathologic results:In the SO group,pathological morphology of liver and the structure of liver lobular were normal,there are no cell edema,degeneration and necrosis,lobular central vein without congestion and expansion.Each subgroup of WIR with the prolongation of reperfusion time,pathological morphology of liver was obviously abnormal,the structure of liver lobular was disorder,liver cell morphology was flaky necrosis,extensive cell edema and cell degeneration and steatosis as well as lobular central venous congestion and expansion,in 6h subgroup of WIR was more pronounced.While compared with WIR group,LC group at the same time point on the structure of liver lobular was better,no obvious inflammatory cell aggregates in the periportal as well as no significant liver cell degeneration and necrosis.Conclusion: 1.L-carnitine has protective effects on liver WIRI in rat,its protective effects may be reduced serum ALT,AST levels and ameliorated liver histopathological changes.2.L-carnitine has antioxidant stress effects on liver WIRI in rat,its antioxidant stress effects may be increased the activity of SOD and reduced the content of MDA in liver tissue.3.L-carnitine can further promote the expression of Nrf2 and HO-1 mRNA by activating the Nrf2 / HO-1 pathway,thereby reducing WIRI in rat liver. |
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