Thymosinβ4Alleviates Mouse Liver Ischemia-reperfusion Injury By Activating AKT-Bad Pathway

Objective: As one of the polypeptide, thymosinβ4(Tβ4) plays protectived role inmyocardial ischemia-reperfusion (I/R) injury by down-regulation of inflammatorychemokines and cytokines, but its function in hepatic I/R injury was unclear. Thepresent study aimed to investigate the effect of Tβ4on mouse hepatic I/R injury andits possible mechanism.Methods: One hundred male ICR mice were randomly divided into four groups: shamgroup,70%IR group, saline group and Tβ4group respectively. Serum was collectedfor ALT, AST measurement at1,3,6,12and24h after reperfusion. Liver tissueswere divided into two parts: one part of liver was fixed for HE staining, the other partwas maintained in liquid nitrogen for western blotting and PCR. The expressions ofTβ4, AKT, P-AKT, Bad, P-Bad were tested by Western blotting; the mRNAexpressions of TNF-α and IL-6were detected by PCR; the expression of NF-kB wasmeasured by immunohistochemical method.Results: During the process of liver I/R injury, the expression of Tβ4was decreasedat1,3h and recovered at6h after reperfusion. The levels of ALT and AST in Tβ4group were lower compared with the70%IR and saline group（P<0.05） which alsoshowed alleviated I/R injury as revealed by HE staining. Meanwhile, the expressionsof NF-kB, TNF-α and IL-6were significantly inhibited in Tβ4group. Furthermore,the Tβ4group showed elevated phosphorylation levels of AKT(P-AKT) andBad(P-Bad) at1,3,6h after reperfusion.Conclusion: Tβ4can alleviate mouse hepatic I/R injury through activating AKT-Bad pathway directly and inhibiting the expressions of inflammatory cytokines in mice.