The Effect Of Ursodeoxycholic Acid To AFP-L3and R-GGTmRNA Expression

Background and AimUrsodeoxycholic acid (UDCA) in clinical is used as the first line of hepatic disease drugs because it has the functions of protecting cells, oxidation resistance, resistance to apoptosis and immune adjustment functions.At home and abroad,the researchs show that UDCA can restrain hepatocellular carcinoma cell line, breast cancer line and many kinds of tumor cell lines, other studies have found that it can inhibit the carcinogenic substance to animals in the effect that cause cancer. To explore the effect of ursodeoxycholic acid (UDCA) to AFP-L3and r-glutamine shift enzyme (GGT) gene expression in rat hepatoma model.We disscue deeply the influence of UDCA to hepatocarcinogenesis, and further explaine it has certain preventive effect to liver cancer.ObjectiveSixty Wister rats, male, eight weeks, weight (180±10) g, bought in shandong university animal experiment center.Methods1、Establishing rat hepatoma model:random divided into four groups (1) hepatoma group only24;(2) UDCA group24only;(3) the normal control group10only;(4) UDCA10only control group.Gave Wister rats DEN solutions by intraperitoneal injection (60mg/kg),used4g/L concentrations of UDCA to replace drinking water to rats in intervention group. 2、From the tenth week, executed a number of rats every four weeks,drew blood from the heart (2ml), used ELISA to detect the AFP-L3level in the rat serum.We weight rats, took liver tissue to counting the nodules, calculated liver/weight ratio and did pathology inspection to understand the progress of liver cancer.3、The common polymerase chain reaction (PCR) testing GGTmRNA subtypes (F, H, P) expression of different organizations in normal group and hepatoma group and that of their aortic blood in hepatoma rats.4、Detecting the expression of GGTmRNA-H subtypes by the real-time quantitative (PT-PCR)in each group rats’blood and liver tissue.Results1、At the tenth week, when the rats’liver surface appears nodules, pathological results show that it has liver cirrhosis with dysplasia nodules,false flocculus of liver cells appearing with atypia in early hepatocelluar carcinoma performance. AT the14th weeks, it has liver nodules obviously more than that in tenth week (pathology revealed a typical performance of liver cancer. The tumor rate of hepatoma group was75%(15/20),UDCA group was45%(9/20).Nodules of UDCA group were less than the number of hepatoma group((P<0.05),and liver weight,liver/weight are both lower than those of liver cancer group(P<0.05).2、The distribution of GGTmRNA subtypes:rat liver tissue only expresses F subtypes and H subtypes, but don’t express P subtypes. The detection rate of H subtypes in cancerous tissue was higher than that in normal liver tissue (P=0.001).In the hepatma tissue, GGTmRNA detection rate of positive F subtypes was significantly less than that in normal liver tissues (P=0.021).In rat blood only H subtypes was tested, the detection rate in liver cancer group was46.7%,much higher than normal group (P=0.022)3、At experimental tenth week(early liver cancer), AFP-L3started to rise significantly,and was significantly with the sixth week. In the hepatoma group and UDCA group the value of AFP-L3were significantly higher than that in control group(P<0.05).The level of AFP-L3in UDCA group was lower than the hepatoma group(P<0.05).4At tenth week (early liver cancer) GGTmRNA-H subtypes appears high expression, and has obvious difference with than at sixth week(P<0.05).In hepatoma group and UDCA group, the expression of H subtypes of liver tissue is significantly different with the control group (P<0.05).In the blood and liver tissue, the expression of H subtypes in UDCA group is less than hepatoma group(P<0.05).Conclusion1、UDCA can reduce the AFP-L3level in rat hepatocarcinogenesis and the expressin of GGTmRNA-H in hepatoma tissue and in the blood。It suggested that UDCA can reduce the occurrence of liver cancer and have certain preventive effect to liver tumors.2、The lever of AFP-L3and GGTmRNA-H subtype in early stage of liver cancer increases significantly, and they are sensitive to liver cancer.It suggested that they can be as the predictive index of rat liver cancer.