The Phosphoinositide 3-kinase/ Akt-significancemediates Proliferation Of Hepatic Sinusoidal Endothelial Cells Of Rat After Partial Hepatectomy

Liver regeneration is controlled by multiple signaling pathways induced by a variety of growth factors, hormones,and cytokines.Two-thirds partial hepatectomy(PHx) is the most commonly used experimental model to study live regeneration.What triggers the initiation of liver regeneration after partial hepatectomy is still unknown. Liver regeneration is a complicated process in which hepatocytes and nonparenchymal cells as well as many cytokines are involved. But it is still unclear what roles hepatocytes and nonparenchymal cells act respectively after PHx and which one is the initial cell although Kupffer cell and fat-storing cell have been explored deeply.Researches found that hepatic sinusoidal endothelial cell(HSEC) can synthesize and release a lots of factors such as HGF,IL-6 and NO to regulate other nonparenchymal cells(NPC) and hepatocyte. Hepatocyte growth factor(HGF) is the first blood-derived mitogen being identified as initiator for proliferation of hepatocyte and the main factor to drive cell cycle from stage G1 to S. HGF is secreted by nonparenchymal cell, such as hepatic sinusoidal endothelial cells, fat-storing cell and Kuffer cell and can stimulate regeneration of hepatocyte through paracrine and autocrine pathway. HGF has also been found having the effect of keeping stability of hepatocyte membrane. Interleukin-6( IL-6), a cytokine produced by liver and intestine cell, has been identified to be indispensable to liver regeneration. When transfected with human IL-6 gene, hepatocytes of Chinese hamster proliferate spreadly and result in increase of liver volume, which suggests that IL-6 may act as mitogen after PHx to trigger hepatocyte regeneration. IL-6 can induce STAT3 into hepatocyte nucleus directly to make early gene activated and initiate mitosis. TNF-α,EGF,TGF-αare aslo blood-derived mitogen for hepatocyte besides IL-6. Blockade of NO synthase using N-nitro-L-arginine methyl ester(L-NAME),a nonselective NOS antagonist,inhibits liver mass regeneration 48h after PHx。In addition,liver proliferation factors,detected in the blood 4h after PHx are inhibited...