[Animal modeling] - Leptin regulates the signal transduction of liver fibrosis in rats and the intervention of mistletoe alkaloid

  Objective: To investigate the signal transduction mechanism of leptin in regulating liver fibrosis in rats and the intervention effect of mistletine.

  Methods: Taking the CCl4-induced liver fibrosis rat model as the research object, 45 rats were randomly divided into three groups, namely the control group, the model group and the drug intervention group. The control group did not do any treatment, and had free food and water; the model group and the mistletine treatment group were injected with 2 mL/kg of 40% CCl4-vegetable oil solution by intraperitoneal injection, twice a week, for a total of 8 weeks. On the ninth week of the experiment, the treatment group was given mistletine 8g/(kg·d) by gavage, and the model group was given the same dose of normal saline by gavage, for a total of 8 weeks. At the 17th week of the experiment, all animals were killed by cervical dislocation, and the left anterior lobe of the liver was removed. HE staining and MASSON staining were used to observe the effect of mistletine on hepatic histomorphology in rats with hepatic fibrosis; the effect of mistletine on leptin and leptin receptors in rat hepatic stellate cells was observed by immunohistochemistry. Western Blot was used to detect the protein levels of JAK2 and STAT3 and the phosphorylation of JAK2 and STAT3 in rat liver tissue.

  RESULTS: The gross liver, HE staining and Masson collagen staining results indicated that the rat liver fibrosis model was successfully replicated, and mistletine had the effect of blocking and reversing liver fibrosis. Immunohistochemical staining showed that compared with the model group, mistletine significantly inhibited the expression of leptin and leptin receptors in the liver tissue of the model rats. Western Blot showed that the expression of JAK2 and STAT3 protein in the normal control group was the least; the expression of JAK2 and STAT3 protein in the model group was high; while the expression of JAK2 and STAT3 protein in the drug treatment group was significantly down-regulated.

  Conclusion: Mistletoe can effectively reverse liver fibrosis in rats, and its mechanism may be achieved by down-regulating the expressions of leptin and leptin receptors in rat liver tissue, thereby affecting the JAK2/STAT3 signaling pathway.