大鼠慢性食管炎中细胞因子和黏附分子表达增加。
Increased expression of cytokines and adhesion molecules in rat chronic esophagitis.
作者信息
Hamaguchi Masaki, Fujiwara Yasuhiro, Takashima Takashi, Hayakawa Tsuyoshi, Sasaki Eiji, Shiba Masatsugu, Watanabe Toshio, Tominaga Kazunari, Oshitani Nobuhide, Matsumoto Takayuki, Higuchi Kazuhide, Arakawa Tetsuo
机构信息
Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
出版信息
Digestion. 2003;68(4):189-97. doi: 10.1159/000075698. Epub 2003 Dec 19.
BACKGROUND/AIMS: Cytokines and adhesion molecules regulate many inflammatory processes in several gastrointestinal diseases. The dynamics of cytokines and adhesion molecules in reflux esophagitis are unknown in detail. We examined the expression and dynamics of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-2, GRO/cytokine-induced neutrophil chemoattractant-2alpha (CINC-2alpha), intercellular adhesion molecule-1 (ICAM-1), leukocyte function-associated antigen 1 (LFA-1; CD11a/CD18), and Mac-1 (CD11b/CD18) in rat chronic reflux esophagitis.
METHODS
Chronic acid reflux esophagitis was induced in Wistar rats by ligating the transitional region between the forestomach and the glandular portion and wrapping the duodenum near the pylorus with a small piece of an 18-Fr Nélaton catheter. Rats were killed 3 or 21 days after operation. The levels of mRNA expression of cytokines and ICAM-1 were determined by real-time quantitative RT-PCR. Localization of adhesion molecules and cytokines was investigated by immunohistochemical staining, and numbers of LFA-1- or Mac-1-positive cells were quantified.
RESULTS
IL-1beta, TNF-alpha, MCP-1, MIP-1alpha, MIP-2, CINC-2alpha, and ICAM-1 mRNA expression was significantly increased in esophageal lesions compared with normal esophagus. There were few these cytokines- or adhesion molecule-positive cells in normal esophagus. In regions of esophagitis, numerous inflammatory leukocytes in lamina propria and the submucosal layer exhibited positive reactions for these cytokines and endothelial cells were intensely stained for ICAM-1. Numbers of LFA-1- and Mac-1-positive cells were significantly increased in rat chronic esophagitis. Treatment with rabeprazole almost completely inhibited development of chronic acid reflux esophagitis and significantly decreased expression of cytokines and ICAM-1 mRNA in esophageal tissue compared with control.
CONCLUSION
Cytokines and adhesion molecules play important roles in the pathogenesis of chronic reflux esophagitis in this rat model.
背景/目的：细胞因子和黏附分子在多种胃肠道疾病中调节许多炎症过程。反流性食管炎中细胞因子和黏附分子的动态变化尚不清楚。我们检测了白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、单核细胞趋化蛋白-1（MCP-1）、巨噬细胞炎性蛋白-1α（MIP-1α）、MIP-2、GRO/细胞因子诱导的中性粒细胞趋化因子-2α（CINC-2α）、细胞间黏附分子-1（ICAM-1）、白细胞功能相关抗原1（LFA-1；CD11a/CD18）和Mac-1（CD11b/CD18）在大鼠慢性反流性食管炎中的表达及动态变化。
方法
通过结扎胃体与腺胃交界处，并将十二指肠幽门附近用一小段18F Nelaton导管包裹，在Wistar大鼠中诱导慢性酸反流性食管炎。术后3天或21天处死大鼠。通过实时定量RT-PCR测定细胞因子和ICAM-1的mRNA表达水平。通过免疫组织化学染色研究黏附分子和细胞因子的定位，并对LFA-1或Mac-1阳性细胞数量进行定量。
结果
与正常食管相比，食管病变中IL-1β、TNF-α、MCP-1、MIP-1α、MIP-2、CINC-2α和ICAM-1的mRNA表达显著增加。正常食管中这些细胞因子或黏附分子阳性细胞很少。在食管炎区域，固有层和黏膜下层大量炎性白细胞对这些细胞因子呈阳性反应，内皮细胞ICAM-1染色强烈。大鼠慢性食管炎中LFA-1和Mac-1阳性细胞数量显著增加。与对照组相比，雷贝拉唑治疗几乎完全抑制了慢性酸反流性食管炎的发展，并显著降低了食管组织中细胞因子和ICAM-1 mRNA的表达。
结论
在该大鼠模型中，细胞因子和黏附分子在慢性反流性食管炎的发病机制中起重要作用。
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