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整合素α4β7在大鼠溃疡性结肠炎发病中的作用 被引量:1

Role of integrin α4β7 in the pathogenesis of ulcerative colitis in rats
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摘要 目的 探讨淋巴细胞归巢受体整合素α4β7在溃疡性结肠炎(UC)大鼠发病中的作用.方法 60只SD大鼠分为对照组(20只,仅用丙酮液灌肠)、模型组(2、4-二硝基氯苯丙酮液灌肠,20只)和干预组(造模后即自大鼠尾静脉注入α4抗体,20只).观察大鼠结肠黏膜损伤情况;采用ELISA法检测结肠组织IL-2和IL-6水平;采用RT-PCR检测结肠组织中α4和β7的表达;采用流式细胞技术检测大鼠门静脉血中整合素α4阳性淋巴细胞数.结果 模型组和干预组大鼠结肠组织α4mRNA相对表达量分别为0.68±0.24和0.58±0.37,β7 mRNA的相对表达量分别为0.84±0.37和0.65±0.30,均显著高于对照组(0.15±0.13,0.24±0.62,均P<0.01).模型组和干预组结肠静脉回流血中α4阳性淋巴细胞的比例分别为(76.7±8.2)%和(68.2±7.6)%,显著高于对照组的(14.7±6.7)%(P<0.01).与模型组比较,干预组大鼠结肠组织大体损伤评分、组织学评分、IL-2和IL-6水平均显著降低(均P<0.05).结论 淋巴细胞整合素α4β7的高表达与大鼠的结肠黏膜炎性反应形成有关,阻断整合素α4β7可有效减轻结肠黏膜炎性损伤. Objective To investigate the role of integrin α4β7 in the development of ulcerative colitis (UC) in rats. Methods Sixty Spague-Dawley rats were randomly divided into the control group (acetone enema), the model group (2,4-dinitrochlorobenzene, DNCB enema), and the α4 intervention group. Colonic mucosa of different groups was observed and compared in terms of pathology and cytokine changes (IL-2 and IL-6) using ELISA. Semi-quantitative RT-PCR was used to detect the colon α4β7 expression. Integrin α4β7 (+) lymphocytes in the portal vein of rats were determined by flow cytometry. Results The expression of α4 mRNA was 0.68±0.24 in the model group and 0.58±0.37 in the intervention group, and the expression of β7 mRNA was 0.84±0.37 in the model group and 0.65±0.30 in the intervention group, which were all significantly higher as compared to those in the control group (0.15±0.13 for α4 and 0.24±0.62 for β7, P〈0.01). The proportions of integrin α4β7 positive lymphocytes in the portal vein in the model group and intervention group were significantly higher than that in the control group [(76.7±8.2)% and (68.2±7.6)% vs. (14.7±6.7)%, P〈0.01]. The expression of IL-2 and IL-6 and the result of macroscopic and microscopic scores in the intervention group were lower than those in the model group (P〈0.05). Conclusions High expression of α4β7 may play an important role in experimental colon mucosa inflammation in rats with ulcerative colitis. The blockade of integrin α4β7 may be a potential target to reduce colonic mucosa inflammation.
出处 《中华胃肠外科杂志》 CAS 北大核心 2010年第12期926-929,共4页 Chinese Journal of Gastrointestinal Surgery
基金 国家自然科学基金(30470794)
关键词 溃疡性结肠炎 淋巴细胞归巢 整合素α4β7 模型 动物 Ulcerative colitis Lymphocyte homing Integrin α4β7 Models, animal
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