Potentiation of Liver Function Recovery and Its Regeneration by the Modulation of Extracellular Matrix During the Early Phase after Liver Transplantation

1)长期饮酒增强了大鼠肝脏产生细胞因子诱导的中性粒细胞趋化因子(CINC)的能力：大鼠以含乙醇或葡萄糖的液体饲料配对喂养6-8wk。给予脂多糖(LPS)，检测肝脏趋化因子mRNA的表达。乙醇灌胃2小时和6小时后，肝组织中CINC基因的表达水平明显高于对照组。注射脂多糖后2小时，雌性大鼠肝脏中CINC基因的表达水平高于雄性大鼠。结果表明，性腺切除完全消除了肝脏CINC基因表达的性别差异。2)酒精性脂肪肝不同程度地诱导CINC和缺血再灌流后肝组织坏死：接下来，我们研究了酒精性脂肪肝从转录因子激活到肝组织坏死的一系列事件，包括转录因子激活、细胞因子诱导和细胞凋亡。与非酒精性脂肪肝或对照组相比，酒精性脂肪肝大鼠在I/R后出现严重的肝坏死。与正常对照组相比，2种脂肪肝模型大鼠肝细胞凋亡明显增加。酒精性脂肪肝在I/R后1h，NF-κB结合活性迅速升高，随后出现α和CINC的表达增加。相比之下，非酒精性脂肪肝在I/R后既没有发现NF-κB的激活，也没有细胞因子的诱导。我们的结果表明，酒精性脂肪肝可以不同程度地诱导I/R后CINC的产生和肝脏的坏死。此外，本研究还表明，当中性粒细胞被激活并聚集到肝脏时，细胞凋亡与肝坏死的进展有关。

1) Long-term ethanol consumption enhances an ability to produce cytokine-induced neutrophil chemoattractant (CINC) in the rat liver : Rats were pair-fed a liquid diet containing ethanol or dextrose for 6-8 wk. They were given lipopolysaccharide (LPS) and chemokine mRNA expression in the liver was evaluated. CINC mRNA expressions in the liver after 2 and 6 hr were significantly higher in the ethanol-fed group than the control. Female alcoholic rats showed higher level of CINC mRNA in the liver than the male rats 2 hr after LPS injection. It was shown that gonadectomy totally abolished the gender difference in CINC mRNA of the liver. We conclude that CINC induction may be responsible for alcoholic hepatitis, and that the difference in ability to produce CINC is a factor contributory to the gender-difference of alcoholic liver disease.2) Alcoholic fatty liver differentially induces CINC and hepatic necrosis after ischemia-reperfusion (I/R) : Next, we investigated a cascade of events from transcription factor activation to necrosis through cytokine-induction and apoptosis in fatty liver after I/R. Rats with alcoholic or non-alcoholic fatty liver were subjected to warm I/R and compared with control rats. Rats with alcoholic fatty liver developed severe hepatic necrosis after I/R, compared to rats with non-alcoholic fatty liver or control. Hepatic apoptosis increased in the 2 fatty liver models compared with the control. Alcoholic fatty liver showed a rapid increase in NF-κB binding activity at 1 hr after I/R, which preceded an increased expression of TNF-α and CINC. In contrast, non-alcoholic fatty liver showed neither NF-κB activation nor cytokine induction after I/R. Our results indicate that alcoholic fatty liver may differentially induce CINC production and hepatic necrosis after I/R. Furthermore, the present study suggests that apoptosis be responsible for the progression to hepatic necrosis when neutrophils are activated and recruited to the liver.