Abstract:
Objective To evaluate the effect of nodosin, as an effective element extracted from rabdosiae serrae, on hepatocyte regeneration after partial liver transplantation.
Methods Wistar rats were used as donors and SD rats as recipients. Rat models with partial liver transplantation were established by modified two-cuff technique. Twenty-four recipient rats were randomly assigned into the nodosin and control groups. In the nodosin group, nodosin at a dosage of 100 μg/ml was administered via tail venous route after liver transplantation. Peripheral plasma and liver specimen were obtained at postoperative 3 and 7 d. The levels of alanine transaminase (ALT), aspartate aminotransferase (ALT) and albumin (ALB) in the peripheral plasma were measured by spectrophotometry. Hepatic histomorphological changes were observed under light microscope. The positive cell count of proliferating cell nuclear antigen (PCNA) antibody in the liver tissue was detected by immunohistochemistry. The expression levels of phosphorylated protein kinase (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR), cyclin D1 and heme oxygenase (HO)-1 proteins were measured by western blot. The apoptosis of liver cells was detected by Annexin V method and TdT mediated-dUTP nick end labeling (TUNEL).
Results Compared with the control group, the serum levels of ALT and AST were significantly lower at 3 d and 7 d after operation, whereas the ALB content was significantly higher in the nodosin group (all in P < 0.05). And nodosin could alleviate the pathological injury of rat liver tissue after transplantation. The positive cell count of PCNA in the nodosin group was significantly higher than that in the control group (P < 0.05). In the nodosin group, the expression levels of p-AKT, p-mTOR, cyclin D1and HO-1 proteins were significantly higher than those in the control group(all in P < 0.05). The quantity and percentage of apoptotic hepatocytes in the nodosin group were significantly lower than those in the control group (both in P < 0.05).
Conclusions Application of nodosin can decrease the quantity of apoptotic hepatocytes and accelerate hepatocyte proliferation after liver transplantation in rat models.