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SDUDIES OF HIGH MOLECULAR SUBSTANCE- SOD CONJUGATE ON PREVENSION OF HEPATIC ISCHEMLA-REPERFUSION INJURY AND HEPATIC MICROCIRCULATION

高分子物质-SOD结合物预防肝缺血再灌注损伤及肝微循环的研究

基本信息

批准号：
08671410
负责人：
TODOROKI Takeshi
金额：
$ 1.47万
依托单位：
UNIVERSITY OF TSUKUBA
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

项目摘要

A protective effects of the SOD (superoxide dismutase)-DIVEMA(divinyl ether and maleic anhydride) conjugate on hepatic ischemia-reperfusion injury was demonstrated. Twenty min. of normothermotic ischemia was induced by clamping the portal triad of Sprangue-Dawley rats. SOD, SOD-DIVEMA, or physiologic NaCl was administered 5 min. prior to reperfusion. Hepatic microcirculation was obserbed during the 120 min. reperfusion period using intravital-fluoresent microscope and events were'recorded to video system for the later analysis. SOD- DIVEMA restored the sinusoidal perfusion rate (98.5% for SOD-DIVEMA vs. 98.0% for no-ischemia, 65.5% for NaCl and 81.5% for SOD administration), and reduced the number of leukocyte stagnant in the acini (12.3 cells/lobule for SOD- DIVEMA vs. 4.4 for no-ischemia, 36.6 for NaCi, 27.7 for SOD administration) and adherent it in the postsinusoidal venule (40.0 cells/mm^2 for SOD-DWEMA vs. 55.0 for no-ischemia, 417 for NaCl and 253 for SOD administration) significantly in comparing control studies. Furthermore, SOD-DIVEMA maintained postischemic hepatocellular integrity . The SOD-DIVEMA treated group maintained significantly higher serum level of SOD activity after 120 min. of reperfusion than the SOD treated group ; 33.0 U/ml vs. 8.6 U/mi. The demonstration of the most beneficial efficacy of SOD-DIVEMA after the period of 120 min. of repercussion indicats a longer intravascular SOD activity than sole SOD administration.

超氧化物歧化酶（SOD）-二乙烯基醚和马来酸酐（DIVEMA）偶联物对肝脏缺血再灌注损伤有保护作用。通过夹闭Sprangue-Dawley大鼠的门静脉三联体诱导20分钟的常温缺血。再灌注前5分钟给予SOD、SOD-DIVEMA或生理NaCl。用荧光显微镜观察再灌注120分钟内肝脏微循环的变化，并记录到录像系统中。SOD- DIVEMA恢复了窦状隙灌注率（SOD-DIVEMA组为98.5%，无缺血组为98.0%，NaCl组为65.5%，SOD组为81.5%），并减少了腺泡中滞留的白细胞数量。（SOD-DIVEMA为12.3个细胞/小叶，无缺血为4.4个，NaCl为36.6个，27.7），并将其粘附在窦后小静脉中（SOD-DWEMA组为40.0个细胞/mm ^2，无缺血组为55.0个细胞/mm ^2，NaCl组为417个细胞/mm ^2，SOD组为253个细胞/mm ^2）。此外，SOD-DIVEMA维持了缺血后肝细胞的完整性。再灌注120分钟后，SOD-DIVEMA治疗组的血清SOD活性水平显著高于SOD治疗组; 33.0 U/ml vs. 8.6 U/ml。在120分钟的反弹期后，证明了SOD-DIVEMA的最有益功效，表明血管内SOD活性比单独SOD给药时间更长。