【作者】 姚文柱；

【导师】 胡家露； 吴开春；

【作者基本信息】 第四军医大学 ， 内科学消化系病， 1999， 博士

【摘要】 消化道粘膜是体内抵御外来抗原的主要屏障，其自身存在着完善的再生及修复机制，几乎每48-72小时消化道粘膜上皮就更新一次。至于其再生及修复的机制目前尚不十分清楚。许多消化道疾病如炎症性肠病、非热带口炎性腹泻等可能就是因为粘膜的修复机制遭到了破坏，导致了长时间的粘膜不能愈合。现在许多学者认为，消化道粘膜免疫系统可能参与了粘膜损伤后愈合的调节。根据解剖学基础，消化道粘膜免疫系统包含了体内最庞大的淋巴细胞系统，且具有不同于其它外周免疫系统淋巴细胞的发生机制和生物学效应。为了探索消化道粘膜免疫系统和粘膜损伤后修复的关系，我们利用感染巴西日圆线虫(Nippostrongylus brasiliensis，Nb)的大鼠肠道粘膜损伤修复过程作为消化道粘膜损伤修复的模型，分析了肠粘膜在损伤后不同阶段部分细胞因子的表达、分布，观察了肠粘膜上皮细胞间淋巴细胞亚群的变化，并对肠段部分细胞因子的mRNA进行了定量分析，初步探讨了肠粘膜免疫系统对粘膜损伤后修复的调节作用。主要内容如下： 1．肠粘膜损伤修复模型的复制。根据文献，剖腹手术后，将500条Nb成虫通过18号注射针头注入正常6周龄SD大鼠十二指肠部位。4天后，大鼠小肠发生明显水肿，肠腔充满潴留液，肠绒毛发生萎缩，杯状细胞数目减少，隐窝细胞增生；8天后，可见绒毛再生，杯状细胞数目增加；16天后，肠道Nb更多还原

【Abstract】 The gastrointestinal epithelium plays a vital part as a barrier against luminal acid, proteolytic enzymes, and ingested noxious agents. This barrier function is partly dependent on constant renewal of the epithelium which is comprise of a population of highly dynamic epithelial cells with nearly complete turnover every 24 to 96 hours. The balance of proliferative activity with commitment to differentiation and loss of mature cells from the villus requires exquisite mechanisms to regulate this complex system. Findings over the past decades have shown that the mucosal immune system is distinct from the normal immune system and an increasing evidence has suggested that it plays important roles in the pathogenesis and protection of the gastrointestinal epithelium. To explore the regulating mechanism of the mucosal immune system during the process of the epithelial damage and healing ,we sought a model in which epithelial damage and healing resembles some pathological conditions of unknown etiology found in man, e.g. ulcerative colitis. The model is produced by Nippostrongylus brasiliensis infections in rats. Using the flow cytometry, we found that the CD4/CD8 ratio in interepithelial lymphocytes (IEL) was increased by 2-fold on day 4 and 8 post-infection, whereas no significant changes in the CD4/CD8 ratio was observed in mesenteric更多还原