Effect of liver I kappa B kinase during hepatic ischemia reperfusion in rats / 中国医师杂志

ABSTRACT

Objective To explore the effect of I kappa B kinase (IKK) on liver during hepatic ischemia reperfusion (HIR) in rats.Methods Wister rats were divided randomly into HIR group in which hepatic reperfusion was given after 60 minutes of ischemia by interruption of the arterial and portal venous blood supply to the left lobes and middle lobes of the liver; HIR + PDTC treatment group in which PDTC (120 mg/kg) were injected via the dorsum vein of penis before ischemia reperfusion; and sham control group in which midline laparotomy was performed without vascular occlusion and treatment.Expression levels of IKK were measured with In situ hybridization(ISH).The NF-κB activities were determined with EMSA.Expression levels of TNF-α were measured with immunohistochemistry (IH).Serum levels of ALT were measured.Results Expression level of IKK was increased markedly from 0 to 12h and peaked 6h after reperfusion in HIR group.NF-κB was activated 0 ～ 12h after reperfusion and activities of NF-κB were maximal 6h after reperfusion in HIR group rats compared with sham control group.Expression level of TNFα was increased markedly from 0 to 12h and peaked 6h after reperfusion in HIR group.Serum levels of ALT were increased significantly after reperfusion in H1R group.Expression level of IKK was lowered markedly in HIR + PDTC group from 0 to 12h after reperfusion.NF-κB activities were significantly lower in HIR +PDTC group than in HIR group from 0 to 12h after reperfusion.Expression level of TNF-α was lowered markedly in HIR + PDTC group as compared with HIR group from 0 to 12h after reperfusion.Serum level of ALT was decreased significantly after reperfusion in HIR + PDTC group as compared with HIR group.Conclusion HIR can activate IKK-β which promotes the activation of NF-κB,then NF-κB results in upregulation transcription of TNF-α gene which gives rise to the release of other inflammatory cytokines and triggers uncontrolled inflammatory response,and induces hepatic injury.Blocking IKK-NF-κB pathway may be an effective approach to checking the generation and development of ALI,PDTC plays important prophylaxis and treatment roles in hepatic injury after HIR.