ABSTRACT
Objective To verify whether β-arrestin-2 inhibits autophagy by up-regulating PI3K/Akt signal to protect the liver from ischemia-reperfusion injury (IRI) in mice. Methods Twelve β-arrestin-2 knockout (KO) and twelve wild-type (WT) C57BL/6 mice were randomly divided into the KO+sham group, KO+IRI group, WT+sham group and WT+IRI group, six mice in each group. The mouse models with 70% liver IRI were established or sham operation was performed. Relevant experiments were carried out at 6 h after liver reperfusion or operation. The expression levels of apoptosis signal protein cleaved Caspase-3, proliferation signal protein Ki-67 and the PI3K/Akt signal protein p-Akt were detected by immunohistochemical staining. Results Immunohistochemical staining demonstrated that compared with the corresponding sham group, the positive cell count for cleaved Caspase-3, Ki-67 and p-Akt in liver tissues of mice was significantly increased in the KO+IRI and WT+IRI groups (all P < 0.01). Compared with the WT+IRI group, the positive cell count for cleaved Caspase-3 in liver tissues of mice was significantly increased, whereas the positive cell count forKi-67 and p-Akt was significantly decreased in the KO+IRI group (both P < 0.05). Conclusions β-arrestin-2 can mitigate the liver cell apoptosis and promote the repair of injury after IRI in mice. Moreover, β-arrestin-2 inhibits autophagy by up-regulating the PI3K/Akt signal to alleviate liver IRI in mice.
ABSTRACT
Objective To evaluate the safety and efficacy of individualized treatment of splenorenal shunt during liver transplantation. Methods Clinical data of 2 recipients who underwent orthotopic liver transplantation and splenorenal shunt intraoperatively were retrospectively analyzed. According to the perfusion status after splenorenal shunt and donor liver reflow, the left renal vein ligation and splenorenal shunt vessel ligation were performed in two recipients during liver transplantation. The general postoperative conditions of the recipients were observed, including surgical related complications, peak portal blood flow velocity, liver and renal function indexs. The postoperative conditions of the recipients were monitored by abdominal ultrasound. Results No intraoperative or postoperative complications occurred in two recipients. The changes of peak portal blood flow velocity before and after splenorenal shunt in two recipients were 22.9-35.1 cm/s and 24.3-58.8 cm/s respectively. No delayed recovery of alanine aminotransferase (ALT) level was observed in two patients after operation. Case 1 experienced a transient increase in the serum creatinine (Scr), which was recovered to normal at postoperative 13 d. During the postoperative follow-up, ultrasound examination demonstrated that the direction and velocity of portal blood flow were normal and liver perfusion was excellent. Conclusions It is safe and effective to selectively ligate the left renal vein or splenorenal shunt vessels of the recipients with severe splenorenal shunt during liver transplantation.
ABSTRACT
Objective To investigate the expression of zeste white 10 interactor (Zwint) in primary hepatocellular carcinoma (HCC) and its effect on the prognosis of liver transplantation for HCC. Methods HCC tissues, paracancerous tissues and clinical data of 50 liver transplant recipients for HCC were collected. The expression levels of Zwint messenger RNA (mRNA) and Zwint protein in 20 pairs of HCC tissues and paracancerous tissues of 20 liver transplant recipients for HCC were compared using real-time fluorescence quantitative polymerase chain reaction (PCR), Western Blot and immunohistochemistry (IHC). Two HCC cell lines HepG-2 which interfered with the expression of Zwint successfully were selected as si-Zwint-1 group and si-Zwint-2 group, and the blank control was taken as si-NC group. The cell proliferation and cell cycle of various groups were compared using cell counting kit (CCK) -8 experiment, flat-cloning assay and cell cycle experiment. The consistency of the expression of Zwint and cyclin D1 in HCC tissues and cells was analyzed using Western Blot and IHC. The enrolled patients were divided into high expression group (22 cases) and low expression group (28 cases) based on the median of Zwint protein expression level, and the relationship of the expression level of Zwint protein and clinical characteristics, overall survival rate and disease free survival rate of liver transplant recipients for HCC was analyzed. Results The results of real-time fluorescence quantitative PCR showed that the expression level of Zwint mRNA in HCC tissues was higher than that of paracancerous tissues (P=0.03). The results of Western Blot and IHC showed that the expression level of Zwint protein in HCC tissues was higher than that of paracancerous tissues(both P<0.05).After the Zwint gene of HCC cell line HepG-2 was interfered,CCK-8 and flat-cloning assay showed that the cell proliferation potential was significantly weakened (all P<0.01), and the cell cycle arrested at stage G1(all P<0.05). The expression level of Zwint protein was closely related to tumor diameter and tumor, node, metastasis (TNM) staging (all P<0.05). The overall survival rate of liver transplant recipients for HCC in the high Zwint expression group was lower than that of the low expression group (P=0.02). Conclusions Zwint is highly expressed in HCC tissues, and it can promote the proliferation of HCC cells through regulating cell cycle. The expression level of Zwint is negatively correlated with the prognosis of liver transplantation for HCC.