Ischaemic preconditioning and the mechanism of increased tolerance to warm ischaemia/reperfusion injury in rat liver

大鼠肝脏缺血预处理及增强热缺血/再灌注损伤耐受机制

• 批准号: 11671271
• 负责人: SHIMAZU Motohide
• 金额: $ 1.86万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671271/
• 关键词: ischaemic preconditioning; ischaemia reperfusion; tumor necrosis factor; microcirculation; TNFα産生; 肝虚血再灌流障害

Background : Brief periods of hepatic ischaemia produces immediate tolerance for subsequent prolonged ischaemia. Although the beneficial effect of this ischaemic preconditioning (IPC) is recognized, the mechanism itself remains unclear.Method : Male Wistar rats were divided into two groups : a control group that was subjected to 30 min of ischaemia + following reperfusion, and an IPC group that was subjected to 5 min of ischaemia +5 min of reperfusion +30 min of ischaemia + following reperfusion. In both groups, hepatic enzymes, histological examinations, microfluorographs, tumor necrosis factor alpha (TNFα) protein production (serum and liver tissue) and mRNA expression for TNFα within the liver tissue were analyzed during the course of reperfusion.Results : In the IPC group, I/R injury represented by the elevation or hepatic enzymes, histological degeneration of hepatocytes, and the increase in the number of non-viable cells was markedly reduced. Moreover, endothelial-adherent leukocytes, TNFα protein production and mRNA production were also suppressed in the IPC group.Conclusion : The mechanism underlying the protective effect of IPC in hepatic I/R injury may involve down-regulation of TNFα production and subsequent attenuation of microcircilatory injury.

背景：短暂的肝缺血可立即耐受随后的长期缺血。方法：雄性Wistar大鼠随机分为对照组（缺血30 min+再灌注）和缺血预处理组（缺血5 min+再灌注5 min+缺血30 min+再灌注）。在两组中，肝酶、组织学检查、显微荧光照片、肿瘤坏死因子α（TNFα）蛋白产生检测再灌注过程中血清和肝组织TNFα mRNA的表达。IPC组肝酶升高、肝细胞组织学变性、并且非活细胞数量的增加显著减少。结论：IPC对肝I/R损伤具有保护作用，其机制可能与抑制TNFα的产生，减轻微循环损伤有关。

项目成果

M.Shinoda, M.Shimazu, G.Wakabayashi, M.Tanabe, K.Hoshino and M.Kitajima.: "Ischaemic preconditioning against hepatic microcirculation disturbance after warm ischaemia/reperfusion in rat."Microcirculayion annual. (in English). (2000)

M.Shinoda、M.Shimazu、G.Wakabayashi、M.Tanabe、K.Hoshino 和 M.Kitajima.：“大鼠热缺血/再灌注后针对肝脏微循环障碍的缺血预处理。”年度微循环。

Masahiro Shinoda,Motohide Shimazu: "Ischemic preconditioning against hepatic microcirculation disturbance after warm ischemia/reperfusion in rat"Microcirculation annual 2000. 16. 119-120 (2000)

Masahiro Shinoda，Motohide Shimazu：“缺血预处理对抗大鼠热缺血/再灌注后肝脏微循环障碍”微循环年鉴2000. 16. 119-120 (2000)

篠田昌宏,島津元秀: "肝虚血再灌流傷害に対するischemic preconditioning(IPC)とその機序"侵襲と免疫. 9. 51-56 (2000)

Masahiro Shinoda，Motohide Shimazu：“缺血预处理（IPC）及其对抗肝脏缺血再灌注损伤的机制”《侵袭与免疫学》9. 51-56（2000）。

M.Shinoda, M.Shimazu, G.Wakabayashi, M.Tanabe, K.Hoshino, M.Kitajima.: "Ischemic preconditioning upon ischemia-reperfusion injury and inflammatory cytokine release."Cytoprotection & biology. 17 (in Japanese). 83-85 (1999)

M.Shinoda、M.Shimazu、G.Wakabayashi、M.Tanabe、K.Hoshino、M.Kitajima.：“缺血再灌注损伤和炎症细胞因子释放的缺血预处理。”细胞保护

篠田昌宏: "ラット肝虚血再灌流障害に対するischemic preconditioning効果と炎症性サイトカインの変動"Cyto-protection & biology. Vol.17. 83-85 (1999)

Masahiro Shinoda：“缺血预处理对大鼠肝脏缺血再灌注损伤和炎症细胞因子变化的影响”《细胞保护与生物学》第 17 卷（1999 年）。