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

1.肝缺血/再灌注损伤后的肝再生尽管有大量证据支持肝缺血/再灌流的机制，但对缺血/再灌流后肝再生的作用知之甚少。我以C57BL/6小鼠为实验动物，研究激活素-卵泡抑素系统在肝缺血再灌注损伤后肝再生中的作用。实时荧光定量聚合酶链式反应检测肝脏缺血再灌流过程中激活素基因的表达。再灌流1h内激活素表达增强。血清激活素水平在再灌流早期也有升高。血清样本中的卵泡抑素蛋白水平在激活素蛋白水平之后增加。这些结果表明激活素在肝缺血/再灌流后早期抑制肝细胞再生的启动。激活素-卵泡抑素系统是调控…再生过程的重要调控系统之一更多的是肝脏。内源性白介素13对肝细胞和血管内皮细胞缺血再灌注损伤的保护作用因此，另一种可能是IL-13通过肝细胞和内皮细胞的功能直接调节肝脏的再生。2.实验性胆汁淤积时肝缺血/再灌注损伤的改变。我们实验室先前的研究证实，梗阻性黄疸可增加中性粒细胞渗入肝脏，并显著加重肝缺血/再灌注后肝细胞的损伤。雄性C57BL/6小鼠结扎并切断胆总管造成梗阻性黄疸。梗阻性黄疸小鼠在手术后7天对90分钟的缺血比30分钟的缺血更敏感。与假手术对照组相比，梗阻性黄疸小鼠肝脏缺血再灌流后早期，NF-κB活性和随后产生的促炎细胞因子如肿瘤坏死因子-α显著增加。这些结果表明，梗阻性黄疸通过激活核因子κB而形成炎性级联反应，使肝脏对肝脏缺血/再灌流易感。3.肝脏缺血/再灌注损伤的临床观察术后IL-6、IL-10、巨噬细胞趋化蛋白-1水平和肝脏长时间缺血与术后手术部位感染和肝细胞损伤显著相关。肝脏缺血再灌注损伤可能参与术后感染和器官功能障碍的病理生理过程。较少

1.Liver regeneration after hepatic ischemia/reperfusion injury.Although there is abundant evidence to support the mechanisms of hepatic ischemia/reperfusion, much less is known about the role of regeneration of the liver after ischemia/reperfusion. I used C57BL/6 mice to assess the function of activin-follistatin system in hepatic regeneration after ischemia and reperfusion injury. The expression of mRNA for activin during a time course of liver ischemia/reperfusion was determined by real time PCR methods. Activin expression was increased within 1 hour of reperfusion. Serum levels of activin were also increased after early time point of reperfusion. Follistatin protein levels in serum samples increased just after activin protein levels. 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 … More the liver. Endogenous interleukin-13 protects hepatocytes and vascular endothelial cells during ischemia/reperfusion injury. Thus, an alternative possibility is that IL-13 directly regulates regeneration of the liver through hepatocytes and endothelial cells function.2.Hepatic ischemia/reperfusion injury alterations in experimental cholestasis.Previous studies from our laboratory have established that obstructive jaundice can increase the neutrophil infiltrates into the liver and significantly elevate hepatoceLLular injury after hepatic ischemia/reperfusion. Male C57BL/6 mice underwent ligation and division of the common bile duct to make obstructive jaundice. Obstructive jaundice mice are far more susceptible to 90 minutes ischemia than 30 minutes ischemia 7 day after surgery. NFκB activation and subsequent production of proinflammatory cytokines such as TNF-α were dramatically increased in obstructive jaundice mice in early time point after hepatic ischemia/reperfusion compared to sham controls. These findings demonstrate that obstructive jaundice develops inflammatory cascade through NFκB activation and renders liver susceptible to hepatic ischemia/reperfusion.3.Clinical examination of hepatic ischemia/reperfusion injuryPostopertive levels of interleukin-6,interleukin-10,macrophage chemoattractant protein-1 and long hepatic ischemia were significantly correlated with postoperative surgical site infection and hepatocellular damage. Hepatic ischemia/reperfusion injury is potentially involved in the pathophysiology of postoperative infection and organ dysfunction. Less