Role of shikonin in ischemia-reperfusion injury in rat liver transplantation
Objective To investigate the mechanism of shikonin in ischemia-reperfusion injury(IRI)in rat liver transplantation.Methods Through the stochastic indicator method,36 healthy male SD rats were randomly divided into 4 groups:control(CTRL)and sham operated control(SH),liver trans-plantation(LT),shikonin group(SKLT).There were 6 rats in each group of CTRL and SH,and 6 rats served as donors and 6 rats as recipients for LT and SKLT.A rat orthotopic liver transplantation model was established by the two-sleeve method,and the SKLT group was given 15 mg/kg gavage after surgery.Ser-um and liver tissue were obtained 24 h after operation.Immunohistochemistry was used to detect the protein expression of B lymphocytoma-2 gene(bcl-2),bcl-2 associated X protein(bax)and caspase-3 in liver tis-sues.Western blotting was used to detect the protein expression of large tumor suppressor factor 1(LATS1),serine threonine kinase 3(MST1)and Yes-related protein(YAP)in liver tissues.Comparison of continuous data between two groups was performed by independent samples t-test.Results Immunohis-tochemistry results showed that the proportion of bax and Caspase-3 positive area was significantly reduced in SKLT group as compared with LT group(bax:0.061±0.002 vs.0.084±0.005,t=11.47,P＜0.05;Caspase-3:0.148±0.008 vs.0.210±0.029,t=7.328,P＜0.05),while the proportion of bcl-2 posi-tive area was significantly increased(0.127±0.036 vs.0.069±0.014,t=3.752,P＜0.05).The Western blotting results showed that the expression of LATS1 and MST1 proteins in SKLT group was signifi-cantly increased as compared with LT group(LATS1:1.56±0.141 vs.1.11±0.30,t=5.715,P＜0.05;MST1:1.80±0.38 vs.1.32±0.31,t=4.190,P＜0.05),while the expression of YAP protein was significantly decreased(1.42±0.10 vs.1.80±0.07,t=11.580,P＜0.05).Conclusion Shiko-nin may reduce hepatocyte apoptosis of IRI in rat liver transplantation by activating the Hippo signaling pathway.
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