Objective To investigate the protective effect of melatonin on rat liver injury induced by bile duct ligation. Methods Sixty-four rats were randomly divided into four groups：control group （CN group， n=16）， shamoperation group （SO group， n=16）， bile duct ligation group （BDL group， n=16）， and bile duct ligation with melatonin injection （BDL＋MT group， n=16）. The model of obstructive jaundice was done by ligation of the common bile duct. Melatonin was injected daily （0.5 mg/kg） via peritoneal cavity from 1 d before the operation to 7 d following oper-ation. On day 4 and 8 after the ligation， the plasma levels of total bilirubin （TBIL）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， gamma glutamyl transferase （GGT）， and alkaline phosphatase （AKP） were measured by routine methods. Malonaldehyde （MDA）， superoxide dismutase （SOD）， glutathione （GSH）， catalase （CAT）， and glutathione peroxidase （GSH-Px） in the liver tissue were determined by spectrophtometry， too. Hepatocytes apoptosis was analyzed by terminal deoxynucleotidyl transferase-mediated deoxynuridine triphosphate nick-end labeling （TUNEL） assay. Results Compared with the CN group and SO group， the levels of TBIL， ALT， AST， GGT， and AKP in the plasma， the content of MDA in the liver tissue， and the apoptosis index （AI） in the hepatocyte markedly increased （P＜0.05， P＜0.01）， the content of GSH and the activities of SOD， CAT， and GSH-Px in the liver tissue markedly decreased（P＜0.01） in the BDL group. Compared with the BDL group， the levels of TBIL， ALT， AST， GGT， and AKP in the plasma， the content of MDA in the liver tissue， and the AI in the hepatocyte markedly decreased （P＜0.01）， the content of GSH and the activities of SOD， CAT， and GSH-Px in the liver tissue markedly increased （P＜0.01） in the BDL＋MT group. In the BDL group， the level of MDA in the liver tissue and the levels of TBIL， ALT， AST， GGT， and AKP were positively correlated （P＜0.01）， the content of GSH and the activities of SOD， CAT， and GSH-Px in the liver tissue and TBIL， ALT， AST， GGT， and AKP were negatively correlated （P＜0.01）. The level of MDA in the liver tissue and AI in the hepatocyte was positively correlated （P＜0.01）. The content of GSH and the activities of SOD， CAT， and GSH-Px in the liver tissue and AI were negatively correlated （P＜0.01）. Conclusions The participation of free radical of oxygen in the pathogenesis and severity of cholestasis produced by the acute obstruction of the extra-hepatic biliary duct is likely. The result of the present study indicates that melatonin exerts a protective effect on cholestatic liver injury in rats with BDL. The mechanism of melatonin’s protection on hepatocyte may be through its antioxidant action and by inhibiting hepatocyte apoptosis.
Objective To research the effect of γ-ray released from 103Pd radioactive stent on the expression of Fas gene and its relation with apoptosis of cholangiocarcinoma cell and the significances through the establishment of human cholangiocarcinoma model. Methods The model of nude mouse with implanted human cholangiocarcinoma was established. The mice were divided into study group and control group, 37 MBq 103Pd biliary stent was implanted in the study group and the ordinary metal biliary stent was implanted in the control group. The volume of tumor was measured, the cell apoptosis was detected by the TUNEL method and the expression of Fas gene of the cell apoptosis of the induced human cholangiocarcinoma was checked out by immunohistochemistry staining 10 d after the implantation. Results Compared with the control group, the growing speed of the volume of tumor in study group was significantly reduced (Plt;0.05), the expression positive rate of Fas gene was significantly higher (Plt;0.05), and the apoptotic rate of cancer cells was also higher (Plt;0.01). Conclusions The 103Pd radioactive stent can induce the cell apoptosis in nude mouse model with implanted human cholangiocarcinoma inhibit the cell growth of bile duct cancer and may promote the apoptosis of cancer cells by increasing the expression of Fas gene. It may be helpful for the further study of treatment for bile duct cancer using 103Pd radioactive stent.