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脏再生。尽管有大量证据支持肝脏缺血/再灌注的机制，但对缺血/再灌注后肝脏再生的作用知之甚少。以C57BL/6小鼠为实验对象，研究激活素-卵泡抑素系统在缺血再灌注损伤后肝再生中的作用。实时荧光定量PCR法检测肝缺血再灌注过程中激活素mRNA的表达。再灌注1小时内激活素表达升高。再灌注早期时血清激活素水平升高。血清样品中卵泡抑素水平在激活素水平之后升高。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-卵泡抑素系统是调节肝脏再生过程的重要调控系统之一。内源性白细胞介素-13在缺血/再灌注损伤中保护肝细胞和血管内皮细胞。因此，另一种可能性是IL-13通过肝细胞和内皮细胞功能直接调节肝脏再生。肝缺血/再灌注损伤对实验性胆汁淤积的影响。本实验室前期研究证实梗阻性黄疸可增加肝缺血再灌注后中性粒细胞向肝脏的浸润，显著加重肝细胞损伤。雄性C57BL/6小鼠结扎分裂胆总管，形成梗阻性黄疸。梗阻性黄疸小鼠在术后7天缺血90分钟远比缺血30分钟更容易发生。梗阻性黄疸小鼠在肝缺血/再灌注后的早期时间点，NFκB的激活和TNF-α等促炎细胞因子的产生显著增加。这些研究结果表明，梗阻性黄疸通过NFκB激活产生炎症级联反应，使肝脏容易发生肝缺血/再灌注。肝缺血再灌注损伤的临床检查术后白细胞介素-6、白细胞介素-10、巨噬细胞趋化蛋白-1及肝长时间缺血水平与术后手术部位感染及肝细胞损伤显著相关。肝缺血/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。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