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

1)长期乙醇消耗增强了大鼠肝脏中产生胡萝卜素诱导的中性粒细胞化学引诱物（CINC）的能力：大鼠成对喂食含有乙醇或葡萄糖的液体饮食6-8周。给予脂多糖（LPS），并评估肝脏中趋化因子mRNA的表达。酒精组大鼠肝脏CINC mRNA表达在2和6小时后显著高于对照组。雌性酒精大鼠在注射LPS后2小时肝脏CINC mRNA水平高于雄性。结果表明，性腺切除完全消除了肝脏CINC mRNA的性别差异。我们的结论是CINC的诱导可能是酒精性肝炎的原因，并且产生CINC的能力的差异是导致酒精性肝病性别差异的一个因素。2）酒精性脂肪肝在缺血再灌注（I/R）后不同程度地诱导CINC和肝坏死：接下来，我们研究了I/R后脂肪肝中从转录因子激活到坏死，通过精氨酸诱导和凋亡的级联反应。对酒精性和非酒精性脂肪肝大鼠进行热I/R，并与对照组大鼠进行比较。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后发生了严重的肝坏死。与对照组相比，2种脂肪肝模型的肝细胞凋亡增加。酒精性脂肪肝I/R后1 h NF-κB结合活性迅速升高，先于TNF-α和CINC的表达增加。相比之下，非酒精性脂肪肝I/R后既没有NF-κB激活，也没有细胞因子诱导。我们的研究结果表明，酒精性脂肪肝可能差异诱导CINC的生产和肝坏死后I/R。此外，本研究表明，细胞凋亡是负责的进展，肝坏死时，中性粒细胞被激活，并招募到肝脏。

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.