Extension of limitation on hepatic warm ischemia, with special reference to analysis of the microcirculatory disturbance and the mechanism of ischemic tolerance from the view points of stress responce protein

<Purpose>本研究通过初始瞬态性病变（GGA）进行了研究，以研究化学耐受性的细胞保护效应，即Geranyl-Geranyl-Acetone（GGA）的亚乳头压力或管理，是已知的一种热休克蛋白（HSP）诱导体，使其扩展了Hepatic Warm ischemia限制，并以评估机制性、Hepatic微循环和内皮细胞功能，包括体内到体外。一个更小的智力模型被评估得像一个更好的层次模型。&lt;材料和方法&gt;男性Wistar大鼠被注射到45分钟后的Hepatic ischemia： （1） 20分钟liverischemia优先7天至45分钟;或（2）GGA口头管理200毫克/千克BW优先7或14天至45分钟后。测试了存活率、肝脏功能、肝炎组织血流、历史学发现、Hsp 70和NF-kB （Western blot）的表达，以及孤立的肝炎/非对中的NO-D22 Y-D2 + NO-D23 Y-D2浓度 ... More enchymal cell cultures 8 Griess method）。在拟议模型中，被认为是90分钟的超级中间式阵列，被认为是（1） 30分钟的初始ischemia从7天到90分钟ischemia，（2）GGA的口头管理是14天到90分钟ischemia。<Results>（1）7天生存率：48小时后，45分钟内所有45分钟内的动物都死于灌注、对比、前条件组的死亡率明显高于（83%和75%）。2.在血清中的预调节组、ALT和HA水平，包括血清中的血清、Hepatic血流和历史学发现，包括在Hepatocytes和Endothelial细胞中增加了凋亡，展示了一个显著的改善。3. HSP 70指数是显而易见的，在重复灌注后直接增加到6小时。4. NF-kB的表达和激活被明显地抑制了。5.在预条件组中，没有生产被iNOS抑制。6.通过预条件和适应症被调节，以增加HSP 70表达。<Conclusion>GGA受保护的活体内容细胞失调和口腔管理的I shemic preconditioning和Oral Administration，并改进了后化学活体中的Hepatic microcirculatory disturbance（Hsp 70）。此Hsp 70支持NF-kB，以调节对iNOS的过度生产。通过ischemia或药物稳定的ischemic Tolerance，在较小的肠道中作为良好的肝脏进行预调节。因此，实现体外化学前条件是预期的，以扩大异位症或活体移植，因此在较小的程度上是有益的。

<Purpose> This study was performed to investigate the cytoprotective effect of ischemic tolerance established by initial transient ischemia as a sub lethal stress or administration of Geranyl-geranyl-acetone (GGA),which are known to be one of heat shock protein (Hsp) inducers, make an extension of hepatic warm ischemia limit, and to evaluate the mechanism ischemic tolerance, hepatic microcirculation and endothelial cell function with in vivo to in vitro. Moreover, small intestinal model was evaluated as well as hepatic model.<Materials & Methods> Male wistar rats were subjected to 45 min of hepatic ischemia followed reperfusion : (1) 20 min liver ischemia 7 days prior to 45 min ischemia, or (2) oral administration of GGA 200 mg/kgBW for 7 or 14 days prior to 45 min ischemia. Examined were survival rate, liver function, hepatic tissue blood flow, histologic findings, expression of Hsp 70 and NF-kB (Western blot), and NOィイD22ィエD2 + NOィイD23ィエD2 concentration in isolated hepatocyte/non-par … More enchymal cell cultures 8Griess method). In intestinal models which were subjected to 90 min superior mesenteric artery clumped, preconditioning groups were (1) 30 min initial ischemia 7 days prior to 90 min ischemia and (2) oral administration of GGA 14 days prior to 90 min ischemia.<Results> 1. The 7-day survival rate : all animals of 45 min ischemia were died within 48 hrs after reperfusion, in contrast, preconditioning groups were significantly higher (83% and 75%) respectively. 2. In preconditioning groups, ALT & HA levels in the serum, hepatic blood flow, and histologic findings including increased apoptosis in hepatocytes and endothelial cells showed a significant improvement . 3. Hsp 70 induction was remarkably increased immediately after reperfusion to 6 hrs. 4. The expression and activation of NF-kB were significantly suppressed. 5. The NO production was inhibited by iNOS in preconditioning groups. 6. Intestinal ischemia limit was extended by preconditioning and apoptosis was regulated with increased Hsp 70 expression.<Conclusion> Ishemic preconditioning and oral administration of GGA protected liver sinusoidal endothelial cell dysfunction and improved the hepatic microcirculatory disturbance in the postischemic liver by inducing Hsp 70. This Hsp 70 suppresses NF-kB to regulate the overproduction of NO attribute to iNOS. Preconditioning by ischemia or drugs establishes ischemic tolerance in small intestine as well as liver. Therefore, performing the ischemic preconditioning is expected to be of much benefit to extend hepatectomy, or liver transplantation and so on. Less