Mechanism of liver regeneration from the viewpoints of cytotoxis activity and cell growth factors, and development of a method for enhancement of liver regeneration using glutamine

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Recently, the mechanism of liver regeneration has been studied using the immunological approach. In a hepatectomy model, appearance of self-injuring lymphecytes, accelerated expression of MHC antigens, and infiltration of CD8-positive cells in the liver had been demonstrated in an early stage of regeneration. In our study of transplantion of small intestine, migration of graft-antigen presenting cells into the liver via the portal vein and rejecting reaction there were observed. In these points, the environment for intestine grafting seems to be similar to that for liver regeneration, and an immunological organ-correlation between the liver and the small intestine was demonstrated. Therefore, we considered that liver regeneration phenomenon is a rejecting reaction against self-hepatocytes. However, in a hepatectomy model, no difference was found between the small intestine and the liver at the time of liver regeneration with respect to the dynamics of CTL, NK activity or NKT cells that sho specific distribution in the small intestine and the liver. On the other hand, as clinical application of liver-regeneration enhancement therapy, a hepatectomy model was fed with food containing glutamine at different concentration (0, 2 or 4%). Consequently, on the 7th day after operation, LBR (ratio of weight of the remaining liver to that of body weight) that indicates lliver regeneration in the 2% group was higher than that in the 0% or 4$ group. Since NK activity was significantly high in the 2% group in comparison with that in the 0% and 4% groups, the optimum glutamine concentration was 2%. For the purpose of demonstrating the mechanism of liver regeneration in vivo, cell-growth factors, cell-cycle control factors and transcription-regulating factors pertaining to liver regeneration were examined using a DNA expressions in a short time in analyses of cancer-related genes. Consequently, activation of transcription factors such as STAT3, C/EBPs, Bel-x and IGF was suggested.