Study on the improvement of liver injury by controlling sinusoidal cells and spleen

1）。用TUNEL法和电镜观察了大鼠肝脏冷保存及再灌注过程中的细胞凋亡变化。因此，我们发现，细胞凋亡只发生在窦内皮细胞（SECs）的发生率很高，导致脱离窦壁。这一现象在冷保存再灌注组中明显，而在单独冷保存组中不明显。该实验模型中的细胞凋亡被血管内皮生长因子（VEGF）抑制，所述血管内皮生长因子（VEGF）已被熟知作为存活和增殖分子起作用。此外，我们发现冷藏脂肪肝的SEC相当脆弱，随着冷藏时间的延长，肝细胞内脂肪滴的尺寸变大。这些变化可能是脂肪肝中常见的移植物无功能的主要原因之一。我们证明肝细胞生长因子（HGF）可以改善SEC的损伤，抑制脂肪滴的扩大。此外，我们还发现，在冷应激过程中，各种基因的表达发生了变化。2）通过抑制肝星状细胞的活化来改善肝硬化。以前，我们报道了小G蛋白Rho的效应分子P160 ROCK的抑制剂Y-27632抑制肝星状细胞的活化，并且该化合物抑制了CCL 4诱导的大鼠肝纤维化向肝硬化的发展。在本研究中，我们表明Y-27632改善了上述模型中已经建立的肝硬化，而没有明显的副作用。这一结果可能是治疗肝硬化的一个有希望的策略。

1). Cold preservation and reperfusion injury of the liverApoptotic change in the liver was studied with Tunel method and electron microscopy in the cold preservation and reperfusion of the rat liver. Consequently, we found that apoptosis was occurred exclusively in the sinusoidal endothelial cells (SECs) with high incidence, leading to the detachment from the sinusoidal wall. This phenomenon was detected markedly in the cold preservation followed by reperfusion, but not in the cold preservation alone. Apoptosis in this experimental model was suppressed by vascular endothelial growth factor (VEGF) which has been well known to function as surviving and proliferative molecule. Furthermore, we showed that SEC of the fatty liver with cold storage was quite fragile and the size of the intra hepatocytic fatty droplet became larger in size as the cold preservation time was longer. These changes in the cold preserved fatty liver appeared to be one of the major causes of non-functioning graft which is frequently occurred in the fatty liver. We demonstrated that hepatocyte growth factor (HGF) ameliorated the impairment of SECs and inhibited enlargement of the fatty droplet. In addition, we showed that expressions of various kinds of the genes were changed during the cold preservation.2) Improvement of the liver cirrhosis by inhibition of activation of hepatic stellate cells. Previously, we reported that Y-27632, inhibitor of P160ROCK which is an effctor molecule of small G protein Rho, suppressed an activation of hepatic stellate cells, and that this compound inhibited the development into the liver cirrhosis in the CCL4-induced liver fibrosis of the rat. In the present study, we showed that Y-27632 ameliorated the already-established liver cirrhosis in the above-mentioned model without apparent side effects. This result may be a promising strategy for the liver cirrhosis.