Differential expression of apoptosis-associated genes post-hepatectomy in cirrhotic vs. normal rats

Liver regeneration after partial hepatectomy or liver injury is controlled by a wide variety of growth factors that are proven activators or inhibitor s of hepatocyte proliferation. Liver regeneration post-hepatectomy has been proven to be decreased and delayed in cirrhotic vs. normal liver. Apoptosi s seems to play an important role in cellular proliferation and in liver re generation. Therefore, this study has analyzed the expression of apoptosis- associated genes following 2/3 hepatectomy in cirrhotic vs. normal rats. Ci rrhosis was induced by a weekly intragastric administration of CCl4 for 16 weeks followed by hepatectomy and histological examination of the resected liver. Rats were sacrificed at 6 h, 12 h, 24 h, or 72 h after liver resecti on. The expression of proapoptotic (Bad, Bak, Bax) and antiapoptotic (Bcl-2 , Bcl-XL) genes was analyzed by quantitative RT-PCR. We have observed an ea rly increase in antiapoptotic mRNA levels and a delayed increase in proapop totic mRNA levels in normal liver following hepatectomy. Before resection, proapoptotic mRNA levels were significantly higher in cirrhotic vs. normal liver. After hepatectomy, apoptotic mRNA levels were decreased and delayed as compared with that observed following hepatectomy in normal liver. These results indicate that apoptosis takes place in liver during CCl4-induced c irrhosis and could participate in the impaired regenerative response observ ed in cirrhotic liver.