Role of the bcl-2/bax pathway in hepatocyte apoptosis during acute rejection after rat liver transplantation

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Abstract
It is well established that hepatocytes undergo apoptotic cell death in the course of rejection of liver grafts. The present study was designed to investigate the role of the bcl‐2/bax pathway in liver allograft tissue. Orthotopic liver transplantation was performed in three groups of rats: group 1, a syngeneic combination (Lewis to Lewis), group 2, an allogeneic combination (ACI to Lewis), and group 3, an allogeneic combination (ACI to Lewis) treated with 15‐deoxyspergualin. The number of apoptotic cells identified by the TUNEL method in the grafted liver reflected the severity of acute rejection. In group 1, both bcl‐2 mRNA and bax mRNA were expressed in trace amounts. In group 2, bcl‐2 mRNA was slightly expressed while the expression of bax mRNA rose steadily. In group 3, bcl‐2 mRNA expression levels remained similar to group 1, while bax expression levels exceeded those in group 1, but were less than in group 2. Expression of bcl‐2 mRNA was stationary in comparison with expression of bax mRNA. Significantly higher levels of bax mRNA were expressed from day 4 in group 2 than in group 1 (on postoperative days 4, 6, and 8, P < 0.05, group 2 vs group 1). We also investigated bax protein and results consistent with the mRNA analysis data were obtained. These findings suggest that apoptotic cell death in liver allograft rejection is regulated, at least in part, by bax.