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

• 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

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.

25只狗被用来研究肌肾代谢综合征（MNMS）。腹主动脉结扎缺血24小时后，解除结扎，再灌注前取腔静脉血样。再灌注后30和60分钟。缺血再灌注时CPK、6-酮类PGF_1 α、11-脱氢血栓素B_2水平升高。白细胞（WBC）在再灌注后刚升高，在再灌注后30分钟下降。这被认为是由于白细胞迁移到损伤组织中。下一步，我们研究了大鼠离体股薄肌缺血2hr再灌注1hr后产生自由基的时间过程和来源。用电子自旋共振（ESR）法测定自由基。自由基的强度模式呈现两个峰，第一个峰出现在再灌注后3min (I/R3)，第二个峰出现在再灌注后45min ~ 60min。X0抑制剂（OPF-001 Ootsuka, Japan）组和中性粒细胞减少大鼠组的ESR强度atI/R3和I/R60均受到抑制。髓过氧化物酶（MPO）的活性也在I/R3,20,60时进行测定。在I/R3和I/R60处，MPO活性的增加与自由基强度的两个峰值表现出相同的模式。因此，自由基的第一个ESR峰可能来自内皮细胞，第二个ESR峰可能来自中性粒细胞。然而，据推测，内皮细胞和中性粒细胞之间的相互作用始于再灌注的早期（I/R3）。综上所述，白细胞在骨骼肌缺血-再灌注中起着非常重要的作用，带白细胞过滤器的局部灌注装置可能有助于预防MNMS。

项目成果

矢野 義明: "骨格筋の虚血再潅流モデルにおけるフリーラジカルの経時的変化とその発生源についての実験的考察" 日本血管外科学会雑誌. 1. 41-47 (1992)

Yoshiaki Yano：“骨骼肌缺血再灌注模型中自由基的时间变化及其来源的实验研究”日本血管外科学会杂志 1. 41-47 (1992)。

Yoshiaki Yano: "Time Course and the Source of Free Radicals after Ischemia Reperfusion in Skeletal Muscle" The Japanese Journal of Vascular Surgery. 1. 41-47 (1992)

Yoshiaki Yano：“骨骼肌缺血再灌注后自由基的时间进程和来源”日本血管外科杂志。