Kubes P
Department of Medical Physiology, University of Calgary, Alberta, Canada.
Am J Physiol. 1993 Jan;264(1 Pt 1):G143-9. doi: 10.1152/ajpgi.1993.264.1.G143.
The objective of this study was to assess whether nitric oxide synthesis inhibition affects intestinal barrier function after ischemia-reperfusion of the feline small bowel. Local intra-arterial infusion of the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 25 nmol.ml-1.min-1) was performed in autoperfused segments of cat ileum for 60 min after 90 min of ischemia and 60 min of reperfusion. Epithelial permeability was quantitated by measuring blood-to-lumen clearance of 51Cr-labeled EDTA, and microvascular dysfunction was assessed by measuring the clearance of protein from the vasculature into the interstitium. 125I-labeled albumin clearance from blood to lumen and histology were performed to further characterize the extent of intestinal dysfunction after reperfusion of the postischemic intestine in the presence and absence of L-NAME. Ischemia-reperfusion-induced mucosal and microvascular permeability increases were dramatically augmented by L-NAME infusion, and this effect was reversed by infusion of L-arginine (125 nmol.ml-1.min-1). Initiating L-arginine (but not D-arginine) infusion alone 10 min before reperfusion provided protection against ischemia-reperfusion-induced mucosal barrier dysfunction; however, this was not associated with a reduction in endogenous levels of L-arginine during ischemia-reperfusion. These data suggest that basal nitric oxide production is important in minimizing mucosal and microvascular barrier dysfunction associated with reperfusion of postischemic intestine.
本研究的目的是评估一氧化氮合成抑制是否会影响猫小肠缺血再灌注后的肠道屏障功能。在猫回肠的自身灌注段，于缺血90分钟和再灌注60分钟后，进行局部动脉内输注一氧化氮合成抑制剂NG-硝基-L-精氨酸甲酯（L-NAME；25 nmol·ml⁻¹·min⁻¹），持续60分钟。通过测量⁵¹Cr标记的EDTA从血液到肠腔的清除率来定量上皮通透性，并通过测量蛋白质从血管系统进入间质的清除率来评估微血管功能障碍。进行¹²⁵I标记的白蛋白从血液到肠腔的清除率测定和组织学检查，以进一步表征在有和没有L-NAME存在的情况下，缺血后肠道再灌注后肠道功能障碍的程度。L-NAME输注显著增强了缺血再灌注诱导的黏膜和微血管通透性增加，而这种效应可通过输注L-精氨酸（125 nmol·ml⁻¹·min⁻¹）逆转。在再灌注前10分钟单独开始输注L-精氨酸（而非D-精氨酸）可提供针对缺血再灌注诱导的黏膜屏障功能障碍的保护作用；然而，这与缺血再灌注期间内源性L-精氨酸水平的降低无关。这些数据表明，基础一氧化氮生成对于最小化与缺血后肠道再灌注相关的黏膜和微血管屏障功能障碍很重要。
