Pathophysiology of MNMS due to acute arterial occlusion and development of a local perfusion

急性动脉闭塞和局部灌注引起的 MNMS 的病理生理学

基本信息

批准号：
02454302
负责人：
KANEKO Hiroshi
金额：
$ 4.16万
依托单位：
Hamamatsu University school of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02454302/
关键词：
MNMS ischemia reperfusion injury free radical 急性動脈閉塞症下肢骨格筋虚血再潅流

项目摘要

Twenty-five dogs were used to investigate myonephropathic metabolic syndrome(MNMS). After 24-hour ischemia by ligation of abdominal aorta, the ligation was released and blood sample was taken from the vena cava before reperfusion. Just after reperfusion, 30 and 60 minutes after reperfusion. The levels of CPK, 6-keto PGF_1 alpha, 11-dehydrothromboxane B_2 were elevated during ischemia-reperfusion. White blood cell(WBC) increased just after reperfusion and decreased at 30 minutes after reperfusion. It is considered that this is because WBC migrate into the injured tissue.As the next step, we investigated the time course and the source of the free radicals generated in the rat isolated gracilis muscle after 2hr of ischemia followed by 1hr of reperfusion. Free radicals were measured by electron spin resonance(ESR). The intensity pattern of free radicals showed two peaks, the first peak was at 3min after reperfusion (I/R3) and the second peak lasted from 45min to 60min after reperfusion. The ESR intensities atI/R3 and I/R60 were inhibited in both X0 inhibitor(OPF-001 Ootsuka, Japan) group and neutropenia rat group. Myeloperoxidase(MPO) activity was also measured at I/R3,20,60. The increase at I/R3 and I/R60 in MPO activity showed the same pattern with the two peaks of free radical intensities. Therefore the first ESR peak of free radicals may be derived from the endothelial cells and the second ESR peak from the neutrophils. It is supposed, however, that an interaction between the endothelial cells and neutrophils starts at early phase(I/R3) of reperfusion.In conclusion, WBC play an very important role in ischemia-reperfusion in skeletal muscle and the local perfusion device with a filter for WBC may be useful to prevent MNMS.

二十五只狗被用来研究肌肾病代谢综合征（MNMS）。腹主动脉结扎缺血24小时后，松开结扎，再灌注前从腔静脉采集血样。再灌注后即刻、再灌注后30分钟和60分钟。缺血再灌注期间CPK、6-酮PGF_1α、11-脱氢血栓烷B_2的水平升高。白细胞(WBC)在再灌注后立即升高，并在再灌注后30分钟下降。据认为，这是因为WBC迁移到受损组织中。下一步，我们研究了缺血2小时和再灌注1小时后离体大鼠股薄肌中自由基产生的时间过程和来源。通过电子自旋共振（ESR）测量自由基。自由基的强度模式显示出两个峰值，第一个峰值出现在再灌注后3分钟(I/R3)，第二个峰值持续在再灌注后45分钟至60分钟。 X0抑制剂（OPF-001大冢，日本）组和中性粒细胞减少症大鼠组的I/R3和I/R60的ESR强度均受到抑制。还在 I/R3、20、60 处测量了髓过氧化物酶 (MPO) 活性。 MPO 活性在 I/R3 和 I/R60 处的增加与自由基强度的两个峰表现出相同的模式。因此，自由基的第一个ESR峰可能来自于内皮细胞，而第二个ESR峰则来自于中性粒细胞。然而，据推测，内皮细胞和中性粒细胞之间的相互作用开始于再灌注的早期（I/R3）。总之，白细胞在骨骼肌缺血再灌注和局部灌注装置中发挥着非常重要的作用。 WBC 过滤器可能有助于预防 MNMS。