Retrorsine effects on regeneration and repair of injured liver in mice undergoing partial hepatectomy / 中国组织工程研究

ABSTRACT

BACKGROUND: In many studies, rats were commonly used as models of retrorsine-induced hepatic injury. Some reports have confirmed that retrorsine cannot inhibit proliferation of mouse hepatic cells. Other reports have shown that retrorsine has inhibitory effects on proliferation of mouse hepatic cells. OBJECTIVE: To study the liver regeneration after hepatic injury by creating mouse models treated with partial hepatectomy combination with retrorsine. METHODS: A total of 40 C57BL/6J mice were equally and randomly assigned to 2 groups. In the partial hepatectomy combined with retrorsine group, intraperitoneal injection of retrorsine 70 mg/kg was conducted, twice, within an interval of 2 weeks. Four weeks later, 2/3 hepatectomy was performed. In the partial hepatectomy group, intraperitoneal injection of saline 70 mg/kg was performed, twice, with an interval of 2 weeks. Four weeks later, 2/3 hepatectomy was performed. At 14 days after partial hepatectomy, the restoration of the livers was observed. The liver cell injury was observed at 3, 7 days with hematoxylin-eosin staining. The hepatocyte proliferation was observed at 3 days with BrdU staining. Oval cell proliferation was observed at 3, 7and 14 days with CK19 and C-kit antibody immunohistochemistry.RESULTS AND CONCLUSION: In the partial hepatectomy group, the damaged liver nearly restored to normal at 14 days after partial hepatectomy, and the result was contrary to partial hepatectomy combined with retrorsine group. Hematoxylin-eosin staining demonstrated that significant degeneration changes in hepatic cells in the partial hepatectomy combined with retrorsine group. BrdU staining showed that hepatocyte proliferation at day 3 was significantly determined in the partial hepatectomy group, but few in the partial hepatectomy combined with retrorsine group. CK19 and C-kit immunohistochemistry demonstrated that visible oval cell proliferation was seen in mice of partial hepatectomy combined with retrorsine group. First of all, hepatic oval cells appeared in portal area and differentiated into hepatic cells and bile duct cells, and then grew into the hepatic lobule gradually. These indicated that retrorsine can obviously inhibit hepatocyte regeneration after liver injury in mice. The model of mice treated with retrorsine and partial hepatectomy could induce oval cell proliferation.