Hatoum Ossama A, Binion David G, Otterson Mary F, Gutterman David D
Department of Medicine and VA Medical Center, Medical College of Wisconsin, Milwaukee, USA.
Gastroenterology. 2003 Jul;125(1):58-69. doi: 10.1016/s0016-5085(03)00699-1.
BACKGROUND & AIMS: Inflammatory bowel disease (IBD; i.e., Crohn's disease, ulcerative colitis) is characterized by refractory inflammatory ulceration and damage to the intestine. Mechanisms underlying impaired healing are not defined. Because microvascular dysfunction resulting in diminished vasodilatory capacity and tissue hypoperfusion is associated with impaired wound healing, we hypothesized that microvascular dysfunction may also occur in chronic IBD.
Intact submucosal arterioles from control, involved, and uninvolved IBD specimens were assessed using in vitro videomicroscopy to assess endothelium-dependent vasodilation in response to acetylcholine (Ach) and fluorescence microscopy to detect oxyradicals.
Normal microvessels dilated in a dose-dependent and endothelium-dependent manner to Ach (maximum, 82% +/- 2%; n = 34). Inhibition of nitric oxide synthase with N(G)-nitro-L-arginine methyl ester (L-NAME) reduced maximal dilation to 54% +/- 6% (P < 0.05, n = 7), and further reduction was observed after inhibiting cyclooxygenase (indomethacin; 23% +/- 10%, n = 6). Chronically inflamed IBD microvessels showed significantly reduced Ach-induced vasodilation (maximum, 15% +/- 2%; n = 33), with no effect of L-NAME. Indomethacin eliminated the remaining Ach-induced vasodilation, resulting in frank vasoconstriction (-54% +/- 9%, n = 6). Uninvolved IBD gut vessels and non-IBD inflammatory controls responded in a fashion similar to normal vessels. IBD-involved microvessels generated significantly higher levels of reactive oxygen species compared with control and uninvolved IBD vessels (P < 0.01).
Human intestinal microvessels from chronically inflamed IBD show microvascular endothelial dysfunction, characterized by loss of NO-dependent dilation that may contribute to reduced perfusion, poor wound healing, and maintenance of chronic inflammation.
炎症性肠病（IBD，即克罗恩病、溃疡性结肠炎）的特征是肠道出现难治性炎症性溃疡和损伤。愈合受损的潜在机制尚不明确。由于微血管功能障碍导致血管舒张能力减弱和组织灌注不足与伤口愈合受损有关，我们推测微血管功能障碍也可能发生在慢性IBD中。
使用体外视频显微镜评估来自对照、病变和未病变IBD标本的完整黏膜下小动脉，以评估对乙酰胆碱（Ach）的内皮依赖性血管舒张，并使用荧光显微镜检测氧自由基。
正常微血管对Ach呈剂量依赖性和内皮依赖性舒张（最大舒张率为82%±2%；n = 34）。用N(G)-硝基-L-精氨酸甲酯（L-NAME）抑制一氧化氮合酶可将最大舒张率降低至54%±6%（P < 0.05，n = 7），在抑制环氧化酶后（吲哚美辛；23%±10%，n = 6）观察到进一步降低。慢性炎症性IBD微血管显示Ach诱导的血管舒张明显降低（最大舒张率为15%±2%；n = 33），L-NAME无作用。吲哚美辛消除了剩余的Ach诱导的血管舒张，导致明显的血管收缩（-54%±9%，n = 6）。未病变的IBD肠道血管和非IBD炎症对照的反应方式与正常血管相似。与对照和未病变的IBD血管相比，病变的IBD微血管产生的活性氧水平显著更高（P < 0.01）。
来自慢性炎症性IBD的人肠道微血管显示微血管内皮功能障碍，其特征是一氧化氮依赖性舒张丧失，这可能导致灌注减少、伤口愈合不良和慢性炎症持续存在。
