Effect and mechanism of YAP in hepatic ischemia-reperfusion injury / 器官移植

ABSTRACT

Objective To explore the effect and mechanism of Yes-associated protein (YAP) in hepatic ischemia-reperfusion injury (IRI) of mice. Methods Forty male C57BL/6 mice were randomly divided into the sham operation group (Sham group), lysophosphatidic acid (LPA) + Sham group, IRI group and LPA+IRI group, 10 mice in each group. Liver tissue and serum samples were collected at 6 h after ischemia-reperfusion. The levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected. Histopathological changes and macrophage infiltration of liver tissues were detected by hematoxylin-eosin (HE) staining and immunohistochemical staining. The protein expression level of YAP was detected by Western blot. The messenger ribonucleic acid (mRNA) expression levels of inflammatory cytokines including tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), interleukin (IL)-1 and IL-6 were quantitatively measured by reverse transcription polymerase chain reaction (RT-PCR). Results Western blot results demonstrated that the protein expression level of YAP in the LPA+IRI group was significantly up-regulated than that in the IRI group. Compared with the Sham group, the ALT and AST were significantly higher in the IRI group (both P < 0.05). The serum levels of ALT and AST in the LPA+IRI group were significantly lower than those in the IRI group (both P < 0.05). HE staining revealed that the morphology of hepatocytes was normal in the Sham group and LPA + Sham group. Pathological changes, such as liver congestion, liver cell swelling and structural abnormalities of hepatic lobule, occurred in the LPA+IRI group and IRI group. Compared with the IRI group, pathological changes were alleviated in the LPA+IRI group. RT-PCR indicated that the mRNA expression levels of TNF-α, iNOS, IL-1 and IL-6 in the LPA+IRI group were lower than those in the IRI group (all P < 0.05). Immunohistochemical demonstrated that LPA partially inhibited macrophage infiltration in ischemic tissues after IRI. Conclusions YAP can significantly mitigate hepatic IRI. The mechanism is associated with the regulation of macrophage recruitment and activation.