Effect of thymoquinone on hepatic ischemic-reperfusion injury / 器官移植

ABSTRACT

Objective To investigate the effect and mechanism of thymoquinone on hepatic ischemia-reperfusion injury (IRI).Methods Thirty C57 mice were randomly divided into the sham operation (sham),IRI and thymoquinone (Thy)groups (n =1 0 in each group).At preoperative 1 h,thymoquinone at a dose of 40 ml/kg was administered via intraperitoneal injection in the Thy group.Absolute ethyl alcohol at the same dosage was given via intraperitoneal injection in the sham and IRI groups.Liver IRI mouse models were established in the IRI and Thy groups.Serum and liver specimens were collected at 4 h after reperfusion.Under light microscope,hepatic histopathological changes were observed and assessed by pathological injury grading.Reverse transcription polymerase chain reaction (RT-PCR)was performed to measure the messenger ribonucleic acid (mRNA)expression levels of tumor necrosis factor (TNF)-α,monocyte chemotactic protein (MCP)-1 and interleukin (IL)-6.The expression of TNF-α,MCP-1 and IL-6 proteins in the serum in the serum were assessed by ELISA.The content of malondialdehyde (MDA)in the liver tissue was detected by thiobarbituric acid (TBA).The activity of catalase (CAT),glutathioneperoxidase (GPx)and superoxide dismutase (SOD)in the liver tissue was determined by ELISA.The expression levels of Wnt,β-catenin and p53 proteins were measured by Western blot.Results Compared with the sham group,the liver injury was more severe and the hepatic injury grading was significantly enhanced in the IRI group (P <0.05),the expression of TNF-α,MCP-1 and IL-6 in the liver tissue and serum sample,and MDA, Wnt,β-catenin and p53 in the liver tissue was significantly up-regulated (P <0.05-0.001 ),whereas CAT,GPx and SOD activity in the liver tissue was dramatically reduced (all in P <0.001 ).Compared with the IRI group,the liver injury in the Thy group was slighter and the liver injury grading was significantly decreased (both in P <0.05).The expression levels of TNF-α,MCP-1 and IL-6 in the liver tissue and serum sample,MDA,Wnt,β-catenin and p53 in the liver tissue were significantly down-regulated (all in P <0.05),whereas CAT,GPx and SOD activity was considerably up-regulated in the liver tissue (all in P <0.05).Conclusions Thymoquinone can mitigate liver IRI through alleviating inflammatory response and oxidation stress.The underlying mechanism is correlated with inhibiting the activation of Wnt/β-catenin/p53 signaling pathway.