THE ROLE OF ENDOGENOUS INTOXICATION IN THE REGULATION OF BCL-2 GENE EXPRESSION IN THE DYNAMICS OF EXPERIMENTAL SUBHEPATIC OBSTRUCTIVE JAUNDICE

Abstract

Background. Antiapoptotic gene Bcl-2 blocks cell death, prolongs cell survival in many cellular systems, protects against various cytotoxic effects. Objective – to evaluate the role of endogenous intoxication in the regulation of Bcl-2 antiapoptotic gene expression in the dynamics of experimental subhepatic obstructive jaundice. Material and methods. The subhepatic obstructive jaundice (duration: 1, 3, 5 and 10 days) was simulated in rats by bandaging the common bile duct at the liver gate. Sham operated animals were used as a control group. The concentration of total bile acids, total bilirubin and urea as well as the activity of ALT and AST were determined in blood serum of experimental and control rats. Total RNA was isolated from 1 ml of whole blood. The level of Bcl2 gene expression was performed by real-time PCR (PCR-RT). Results. Over a 10 day-experiment the concentration of total bile acids in blood serum of jaundiced animals has increased 38-74 times (p<0.001), the level of bilirubin - 11.7-18 times (p<0.001), aminotransferase activity and urea concentration have increased significantly. All this leads to endotoxemia, producing a cytotoxic effect on the tissues of the internal environment of the body and is accompanied by enhanced relative level of expression of the antiapoptotic gene Bcl-2. Conclusion. A 10-day-subhepatic obstructive jaundice (the degree of its severity depends on the duration of cholestasis) leads to the development of biliary endogenous intoxication, accompanied by enhanced relative level of expression of the Bcl-2 antiapoptotic gene, that in its turn blocks the development of apoptosis.