Macrolide antibiotics protects against ischemia-reperfusion injury after liver transplantation in rats / 中国组织工程研究

ABSTRACT

BACKGROUND: Liver transplantation is the standard treatment for end-stage liver disease and liver failure. However, ischemia-reperfusion injury can reduce the success rate of liver transplantation. When a limited number of liver donors are available for transplantation, how to reduce liver ischemia-reperfusion injury has become the primary issue in liver transplantation. OBJECTIVE: To evaluate the effect of macrolide antibiotics on ischemia-reperfusion injury after liver transplantation in rats. METHODS: Rat autologous orthotopic liver transplantation model was constructed. Wistar rats were randomly divided into macrolide antibiotics group and control group. In the macrolide antibiotics group, the donor liver was treated with macrolide antibiotics (60 mg/kg roxithromycin, 20 mg/kg clarithromycin and 40 mg/kg erythromycin) 30 minutes before hepatectomy, and the above macrolide antibiotic mixture was injected into the portal vein immediately after orthotopic liver transplantation. In the control group, rats were pretreated with the same volume of saline for 30 minutes before hepatectomy, and the same volume of saline was injected into the portal vein immediately after orthotopic liver transplantation. The survival rate of the rats was observed within 7 days after liver transplantation. The serum aspartate aminotransferase and alanine aminotransferase activities were detected by automatic biochemical analyzer at 48 and 72 hours after liver transplantation. Hematoxylin-eosin staining and immunohistochemistry assay were used to detect the morphological changes of liver tissues and the number of Ki-67 positive cells in liver transplantation rats. TUNEL and western blot assay were used to detect the number of apoptotic hepatocytes and the expression of caspase-3 and cleaved caspase-3 proteins in liver transplantation rats, respectively. The Kupffer cell number changes and levels of interleukin-6, interleukin-1β, and tumor necrosis factor-α in rat liver tissues after liver transplantation were detected by immunofluorescence and ELISA, respectively. RESULTS AND CONCLUSION: Macrolide antibiotics increased the overall survival rate of liver transplanted rats, improved the dysfunction of transplanted liver, reduced the severity of ischemia-reperfusion injury after liver transplantation, increased the regenerative capacity of transplanted liver, reduced the number of apoptotic cells and the ratio of cleaved caspase-3/caspase-3 in the transplanted liver tissue, and decreased the number of Kupffer cells and the levels of interleukin-6, interleukin-1β and tumor necrosis factor-α in the transplanted liver. All the results indicate that macrolide antibiotics protect against ischemia-reperfusion injury in rats undergoing liver transplantation.