Induction of stress protein in the liver upon brain death -changes in sinusoidal microcirculation of the liver and the tolerance acquisition to the ischemia/reperfusion injury

本研究建立了大鼠脑死亡模型。诱发脑死亡后2-3 min脑电图开始降低，脑死亡状态下1-3 h脑电图完全平缓。角膜反射消失。颅内压升高时血压急剧升高，然后迅速下降。此后，稳定的低血压持续至少3小时。符合脑死亡标准。在肝微循环方面，脑死亡模型中白细胞与肝窦内皮的粘附增加，门静脉和肝窦后血管口径变小。白细胞流速明显下降。脑死亡组白细胞CD 11表达明显增强。这些结果与脑死亡状态下由于α刺激阻断而维持肝脏微循环的推测不一致，这是由于脑死亡状态下肝脏微循环的高度维持。 ...更多信息 在犬脑死亡模型中艾德动脉血酮体比率。然而，从脑死亡状态下获得的肝脏在冷保存期间一旦停止能量代谢，移植后血液再灌注时就重新开始。因此，脑死亡过程中某些细胞因子的激活导致微循环的恶化，可能只是导致了肝功能的潜在损害，即肝损害。e.冷缺血再灌注后，肝细胞损伤明显，导致移植肝功能障碍。而在脑死亡过程中热休克蛋白的产生方面，由于脑死亡发生后3小时的时间较短，Western-blot未检测到热休克蛋白72的表达。关于HSP 72的mRNA，即使假手术动物也表达它，这就是为什么在本研究期间不能完全确定库欣现象触发HSP 72表达的作用。通过对脑死亡肝脏维持的特殊微环境和脑死亡状态下细胞水平的应激反应的分析，将有助于我们调控脑死亡肝脏的应激反应，从而发展新的分子外科手术，提高肝移植的成功率。少

Brain-dead model of rats was established in this research. Electro-encephalogram became reduced 2-3 minutes after induction of brain-death and it was completely flat at 1-3 hours during brain-dead state. Corneal reflex was disappeared. Blood pressure showed a steep elevation upon the increase of intracranial pressure and then rapidly decreased. Stable low blood pressure continued thereafter at least for 3 hours. The criteria of brain-death was fulfilled. Concerning the microcirculation of the liver, adhesion of leukocytes to sinusoidal endothelium was increased and the calibers of the portal vein and post-sinusoidal vessels were smaller in the brain-dead model. The flow rate of leukocytes was remarkably decreased. Expression of CD11 of leukocytes was significantly enhanced in the brain-death. These results were not consistent with the speculation of maintained hepatic microcirculation during brain-dead state due to alpha stimulation blockade, which was supposed from the highly maintain … More ed arterial ketone body ratio in the brain-dead model of dogs. However, the hepatic energy metabolism is once discontinued during cold preservation after procurement from brain-dead state aid is restarted upon blood reperfusion after transplantation. It is therefore possible that the deterioration of microcirculation due to activation of some cytokines during brain-death results only in the latent harm of the liver function, i. e. in the range of hepatic functional reserve, and the damage become overt after cold ischemia and reperfusion to produce primary graft dysfunction. As for production of heat shock proteins during brain-death, HSP72 protein was not detected by Western-blot, probably because of short period of 3 hours after the onset of brain-death. Concerning the m-RNA of HSP72, even the sham operated animal expressed it. This is why the effects of Cushing phenomenon to trigger the HSP72 expression could not be fully determined in this study period. The analyses of special microenvironment in which the brain-dead graft is maintained and those of the stress response at cellular level in the brain-dead state will enable us to manipulate the stress response in the brain-dead liver so that we can develop a new molecular surgery to improve liver transplantation. Less