The modulation of transcription factor in liver regeneration after hepatic ischemia/reperfusion

1. 肝缺血再灌注损伤后的肝脏再生。再灌注1小时内激活素mRNA表达及血清水平升高。再灌注后血清样品中卵泡抑素蛋白水平也升高。这些结果表明，激活素在肝缺血再灌注后的早期时间点抑制肝细胞再生的启动。激活素-卵泡抑素系统是肝脏再生过程的重要调控系统之一。肝缺血/再灌注损伤对实验性胆汁淤积的影响。胆汁淤积肝的肝损伤机制尚不完全清楚。雄性C57BL/6小鼠经胆总管结扎后出现梗阻性胆汁淤积。小鼠局部肝缺血90分钟后再灌注。肝缺血再灌注后胆汁淤积肝小鼠的存活率低于正常肝小鼠。进一步的生化和组织学分析表明，胆汁淤积小鼠在再灌注后肝细胞损伤程度明显高于正常小鼠。胆汁淤积肝再灌注后中性粒细胞积累明显减少；然而，在再灌注后，在胆汁淤积的肝脏中观察到相当大的微循环紊乱。用免疫组化染色法观察再灌注后胆汁淤积肝星状细胞活化及内皮素-1的表达。这些观察结果也与血清内皮素-1水平升高有关。肝星状细胞活化和内皮素-1分泌增加在胆汁淤积肝缺血再灌注损伤中起重要作用。肝再生的临床检查。术前门静脉栓塞（PVE）是一种有效的手段，使未来的剩余肝脏肥厚，从而保证肝脏恶性肿瘤广泛肝切除术的安全性。肝脏对PVE的反应包括许多介质的诱导，如生长因子。然而，影响PVE术后肝脏再生的因素尚不清楚。血浆VEGF水平在PVE治疗后明显升高，在PVE治疗第7天达到最高值。血浆tgf - β水平也在PVE后升高，并在第14天达到峰值。PVE治疗7 d后肝脏体积增加%与血浆VEGF水平显著相关。VEGF可影响PVE后肝残叶再生级联的激活。PVE术后血浆VEGF水平的测量可能是潜在肝再生的预测因素，并可能为决定后续肝切除术的时间表提供有用的信息

1. Liver regeneration after hepatic ischemia/reperfusion injury.Activin mRNA expression and serum levels of activin were increased within 1 hour of reperfusion. Follistatin protein levels in serum samples were also increased after reperfusion. These results indicate that activin inhibits initiation of regeneration in hepatocytes at early time point after hepatic ischemia/reperfusion. The activin-follistatin system is one of the important regulatory systems modulating regeneration processes of the liver.2. Hepatic ischemia/reperfusion injury alterations in experimental cholestasis.The mechanism of liver injury in cholestatic liver is not fully understood. Male C57BL/6 mice underwent common bile duct ligation and subsequently developed obstructive cholestasis. The mice were subjected to 90 minutes of partial hepatic ischemia followed by reperfusion. The survival rate of the mice with cholestatic livers after hepatic ischemia/reperfusion was lower than that of the mice with normal livers. … More Biochemical and histological analyses showed that the cholestatic mice had a much higher degree of hepatocellular injury after reperfusion than the normal mice. Neutrophil accumulation after reperfusion was significantly decreased in the cholestatic livers ; however, considerable microcirculatory disturbances were observed in cholestatic livers after reperfusion. Hepatic stellate cell activation and hepatic expression of endothelin-1 were evaluated by immunohistochemical staining in cholestatic livers after reperfusion. These observations were also associated with increased serum levels of endothelin-1. Hepatic stellate cell activation and increased endothelin-1 production play a crucial role in hepatic ischemia/reperfusion injury in cholestatic liver.3. Clinical examination of liver regeneration.Preoperative portal vein embolization (PVE) is an effective means of creating hypertrophy of future remaining liver, which leads to safety of extensive hepatectomy for hepatic malignancies. Hepatic response to PVE includes the induction of numerous mediators such as growth factors. However, the factors affecting liver regeneration after PVE are not clearly understood. Plasma VEGF levels were increased markedly after PVE and were maximal after 7 days of PVE. Plasma TGF-beta levels were also increased after PVE and peaked at 14 days. % increased liver volume was significantly correlated with plasma VEGF level after 7 days of PVE.. VEGF could affect the activation of regenerative cascade in hepatic remaining lobe after PVE.. Measurement of plasma VEGF levels after PVE may be a predictive factor of potential liver regeneration and may provide useful information to decide on the schedule of subsequent hepatectomy Less