The Effect Of Berberine On Intestinal Injury Caused By Autologous Orthotopic Liver Transplantation In Rats

Objective: To explore the protective effects of berberine against intestinal damage caused by autologous orthotopic liver transplantation(OLAT) and its probable mechanism.Methods: We selected twenty-four male healthy Sprague-Dawley rats. They were randomly divided into there groups(n=8):(1) sham group(S group);(2) autotransplantation(AT group);(3) autotransplantation+berberine group(BBR group). In S groups, the rats were anesthetized and simply freed the blood vessels and ligaments. In AT groups, the rats underwent autologous orthotopic liver transplantation. Ringer lactate solution was injected for reperfusion of liver as an inflow tract. The entire anhepatic phase lasted 30 minutes. In BBR groups, berberine was administered intragastricly 200 mg·kg-1·d-1 for 7days before autotransplantation. 8 hours after surgery,the blood of inferior vena cava was obtained to detect the levels of D-lactate and endotoxin. Meanwhile the rats were killed and the intestines were harvested for determination of histologic injury and wet/dry(W/D) ratio. Intestinal tissue homogenate was detect the levels of superoxide dismutase(SOD) and malondialdehyde(MDA). Western blotting detected the protein expression levels of Bax, Bcl-2 and AMPK. The expression level of Cytochrome C was analyzed by the immunochemistry methods. We brought TUNEL method to measure the count of cell apoptosis of intestine tissues. SPSS 17.0 was used to do statistical analysis.Results:Light microscopy demonstrated that histological tissue damage was reduced in the BBR group than in the AT group, while no injury was evident in the S group. D-lactate, endotoxin, W/D ratio, MDA level, protein expression levels of Bax and AMPK, the expression level of Cytochrome C and the count of cell apoptosis were significantly higher in the AT group and BBR group than in the S group. These indicators were significantly higher in the AT group than in the BBR group except protein expression levels of AMPK(P<0.05). The levels of SOD and protein expression levels of Bcl-2 were significantly lower in the AT group and BBR group than in the S group. They in the BBR group were greatly higher than in the AT group(P<0.05).Conclusion: 1. Autologous orthotopic liver transplantation of rats can cause intestinal mucosa edema. Therefore the W/D ratio and the levels of D-lactate and endotoxin increase in the AT group and BBR group. Oxidative stress, cell apoptosis and the activation of AMPK protein may play an important role in the process of autologous orthotopic liver transplantation. 2. Berberine pretreatment can activate the AMPK protein and increase the Bcl-2/Bax ratio. Further it can maintain the mitochondrial membrane stability, reduce the release of cytochrome C and inhibit the occurrence of cell apoptosis so as to alleviate the intestinal ischemia-reperfusion injury.