Platelet-activating factor and nitric oxide mediate microvascular permeability in ischemia-reperfusion injury.
Platelet-activating factor and nitric oxide mediate microvascular permeability in ischemia-reperfusion injury.
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DOI：
10.1006/mvre.1996.0059
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发表时间：
1996-11
影响因子：
3.1
通讯作者：
A. A. Noel-A.;R. Hobson;W. Durán
中科院分区：
文献类型：
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作者：
A. A. Noel-A.;R. Hobson;W. Durán
微血管通透性增加是缺血-再灌注（I/R）损伤的标志。我们推测，血小板活化因子（PAF）和一氧化氮（NO）参与了I/R损伤大分子物质的外渗。为了阻断内源性PAF，我们使用PAF受体拮抗剂（WEB 2086; 2 mg/kg，i.v）。为了抑制内源性一氧化氮，我们使用了NO合酶抑制剂L-NG-单甲基精氨酸（10（-5）M L-NMMA）。我们评估微血管通透性的FITC-葡聚糖150通过测量积分光强度（Δ IOI）的变化，使用计算机辅助图像分析在仓鼠颊囊。我们检查了每个囊袋中的一个缺血区域和一个对照区域。诱导缺血2小时，然后再灌注1小时。调查了六个群体。第1组（n = 5）不进行药物干预;第2组（n = 5）在再灌注前15 min输注WEB 2086;第3组（n = 5）在再灌注时输注WEB 2086;第4组（n = 5）在再灌注开始后15 min输注WEB 2086。第5组（n = 3）接受局部L-NMMA（再灌注前30分钟，并在实验的剩余时间内持续）。第6组（n = 3）接受L-NMMA（如第5组）和WEB 2086（再灌注后15分钟给药）。在第1组中，I/R使平均（+/- SEM）Δ IOI值从61.5 +/- 11.1增加至127.2 +/- 26.1。WEB 2086在每个时间点抑制Δ IOI的增加。同样，单独给予L-NMMA和L-NMMA + WEB 2086的组在缺血组和对照组之间没有差异。我们的数据表明：（1）PAF和一氧化氮参与了与缺血-再灌注损伤的微血管功能障碍相关的通透性变化;（2）PAF和一氧化氮合酶抑制剂在缺血期间或再灌注开始后有效减轻大分子外渗。
Increased microvascular permeability is a hallmark of ischemia-reperfusion (I/R) injury. We hypothesized that platelet-activating factor (PAF) and nitric oxide (NO) are involved in the extrvasation of macromolecules in I/R injury. To block endogenous PAF, we used a PAF-receptor antagonist (WEB 2086; 2 mg/kg, i.v). To inhibit endogenous nitric oxide, we employed L-NG-monomethyl arginine (10(-5) M L-NMMA), a NO synthase inhibitor. We assessed microvascular permeability to FITC-dextran 150 by measuring changes in integrated optical intensity (delta IOI) using computer-assisted image analysis in the hamster cheek pouch. We examined one area of ischemia and one control area in each pouch. Ischemia was induced for 2 hr and was followed by 1 hr of reperfusion. Six groups were investigated. Group 1 (n = 5) had no pharmacologic intervention; Group 2 (n = 5) received WEB 2086 15 min before reperfusion; Group 3 (n = 5) received WEB 2086 at reperfusion; Group 4 (n = 5), WEB 2086 was infused 15 min after the onset of reperfusion. Group 5 (n = 3) received topical L-NMMA (30 min prior to reperfusion and continuously for the remainder of the experiment). Group 6 (n = 3) received both L-NMMA (as in Group 5) and WEB 2086 (administered 15 min after reperfusion). In Group 1, I/R increased the mean (+/- SEM) delta IOI value from 61.5 +/- 11.1 to 127.2 +/- 26.1. WEB 2086 inhibited the increase in delta IOI at each time point. Similarly, the groups given L-NMMA alone and L-NMMA + WEB 2086 showed no difference between ischemic and control groups. Our data demonstrate that (1) PAF and nitric oxide are involved in the permeability changes associated with the microvascular dysfunction of ischemia-reperfusion injury; (2) inhibitors of PAF and nitric oxide synthase are effective in attenuating macromolecular extravasation when given during ischemia or after initiation of reperfusion.