Hanabata Norihiro, Sasaki Yoshihiro, Tanaka Masanori, Tsuji Tsuyotoshi, Hatada Yasumasa, Hada Ryukichi, Munakata Akihiro
First Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki 036-8502, Japan.
Scand J Gastroenterol. 2005 Feb;40(2):188-93. doi: 10.1080/00365520410010580.
Vascular endothelial growth factor (VEGF) expression and microvessel parameters have not yet been quantified in the colonic mucosa of ulcerative colitis (UC). The aim of this study was to correlate the parameters with clinical responsiveness to steroid therapy.
Colorectal biopsy specimens from 39 UC patients with high sensitivity to steroid (H-UC), 9 UC patients with low sensitivity to steroid (L-UC) and 6 normal controls (NC) were examined.
Tissue sections were immunostained with anti-VEGF antibody for number of inflammatory cells (/mm(2)), VEGF-positive cell (/mm(2)) and VEGF-positive ratio (%), and with CD34 for microvessel counts (/mm(2)) and the mean microvessel diameter (microm).
The H-UC group had a significantly larger total cell count (10,048+/-2751, p<0.0001) or VEGF-positive cells (2363+/-707, p<0.0001) than the NC group (7235+/-2088 or 1537+/-297, respectively) with no difference in VEGF-positive ratio (24.3+/-6.9 for H-UC versus 22.7+/-6.9 for NC). The L-UC group had a significantly lower VEGF-positive cell count (1420+/-701, p<0.0005) or VEGF-positive ratio (11.6+/-5.5, p<0.0005) than the H-UC group, whereas microvessel counts were almost constant regardless of the subject groups (345+/-7 0 for NC versus 346+/-99 for H-UC versus 349+/-114 for L-UC). Significant increases in microvessel diameter were seen when comparing NC (6.68+/-0.60) with H-UC (7.83+/-1.09, p<0.0001) and H-UC with L-UC (9.05+/-1.70, p<0.03). Out of the five parameters, VEGF-positive ratio and microvessel diameter had a predictive value for L-UC with an 88.9% sensitivity and 88.9% specificity.
L-UC was characterized either as VEGF underexpression or enlarged microvessel. The disruption of the healing process or disturbance of microcirculation may be involved in low sensitivity to steroid therapy in UC.
尚未对溃疡性结肠炎（UC）结肠黏膜中的血管内皮生长因子（VEGF）表达及微血管参数进行量化。本研究旨在将这些参数与类固醇治疗的临床反应性相关联。
对39例对类固醇高敏的UC患者（H-UC）、9例对类固醇低敏的UC患者（L-UC）及6例正常对照（NC）进行结直肠活检标本检查。
组织切片用抗VEGF抗体免疫染色，以检测炎症细胞数量（/mm²）、VEGF阳性细胞（/mm²）及VEGF阳性率（%），并用CD34检测微血管计数（/mm²）及平均微血管直径（μm）。
H-UC组的总细胞计数（10,048±2751，p<0.0001）或VEGF阳性细胞（2363±707，p<0.0001）显著多于NC组（分别为7235±2088或1537±297），VEGF阳性率无差异（H-UC组为24.3±6.9，NC组为22.7±6.9）。L-UC组的VEGF阳性细胞计数（1420±701，p<0.0005）或VEGF阳性率（11.6±5.5，p<0.0005）显著低于H-UC组，而微血管计数在各受试组中几乎恒定（NC组为345±70，H-UC组为346±99，L-UC组为349±114）。与NC组（6.68±0.60）相比，H-UC组微血管直径显著增加（7.83±1.09，p<0.0001），与L-UC组相比，H-UC组微血管直径也显著增加（9.05±1.70，p<0.03）。在这五个参数中，VEGF阳性率和微血管直径对L-UC具有预测价值，敏感性为88.9%，特异性为88.9%。
L-UC的特征为VEGF表达不足或微血管增大。愈合过程的破坏或微循环紊乱可能与UC对类固醇治疗的低敏感性有关。
