Studies on the pathogenesis of early lesions in Crohn's disease : Clinical and experimental investigation

1.临床研究为探讨结肠淋巴结滤泡相关上皮(FAE)在克罗恩病溃疡形成中的作用，对10例克罗恩病患者进行了放大结肠镜、电子显微镜和免疫组织化学检查。结果，放大结肠镜下，淋巴结节周围有红色光晕，没有明显的侵蚀，扫描电子显微镜显示表面侵蚀150-120微米。扫描和透射电子显微镜显示FAE残留，包括侵蚀边缘的M细胞。在免疫组织化学研究中，在克罗恩病活动期的整个炎性结肠粘膜中，人类白细胞抗原-DR的表达强于缓解期。因此，淋巴滤泡周围的红色光晕似乎先于可见的口疮溃疡，并表明克罗恩病的溃疡起源于FAE。炭化…的实验研究用24 mg/kg吲哚美辛灌胃给药大鼠，观察肠隐窝增殖和生长因子表达的早期变化，扫描电子显微镜观察，隐窝增殖(Brd U免疫组织化学染色)和肠组织中转化生长因子-β1、胰岛素样生长因子-1、肝细胞生长因子和神经生长因子的mRNA表达(RT-PCR)。扫描电子显微镜显示，1小时后中、小肠绒毛扭曲变形。中小肠隐窝增殖在2小时后无明显变化，5小时后各部位隐窝增殖均减少。IGF-1和HGF在6h开始明显表达，而NGF在该时间点未检测到。提示吲哚美辛诱导的早期粘膜损伤以隐窝结构改变为特征，但对隐窝细胞增殖无影响，某些生长因子的变化可能在粘膜损伤的发展中起一定作用。较少

1. Clinical investigationTo clarify the role of the follicle associated epithelium (FAE) of colonic lymphoid nodules in the formation of ulcers in Crohn's disease, 10 patients with this disease were studied by magnifying colonoscopy, electron microscopy, and immunohitochemical examination. As a result, scanning electron microscopy of lymphoid nodules surrounded by a red halo without visible erosions by magnifying colonoscopy showed surface erosions 150-120mum in size. Correlation of scanning and transmission electron microscopy revealed residues of FAE including M cells at the edges of the erosions. In immunohistochemical studies, HLA-DR antigen was more strongly expressed in the entire inflamed colonic mucosa in the active stage of Crohn's disease than in the remission stage. Therefore, the red halo appearance surrounding lymphoid follicles seems to preced visible aphthoid ulcers and suggests that ulcerations in Crohn's disease originate from FAE.2. Experimental investigationTo charac … More teriza early changes in both cryptal proliferation and expression of growth factors in indomethacin-induced small intestinal damage, scanning electron microscopic findings, cryptal proliferation (using immunohistochemical staining for Brd U), and intestinal mRNA expression of TGF-beta_1, IGF-1, HGF,and NGF (using RT-PCR) were investigated in rats which were received 24 mg/kg of intracolonic indamethacin. Scanning electron microscopy showed that the villi in the mid-small intestine was distorted with tortuous fashion at an hour. Cryptal proliferation in the mid-small intestine was not altered at 2 hour whereas it was decreased at all sites after 5 hours. IGF-1 and HGF expression became obvious at 6 hour, while NGF could not be detected at this time point. These findings suggest that early mucosal damage induced by indomethacin is characterized by alteration of the crypt architecture without changes in crypt cell proliferation, and that changes of some growth factors may play a role in the progression of the mucosal damage. Less