Th17细胞相关因子在先天性巨结肠相关小肠结肠炎表达的研究

Expressions of Th17-related cytokines in children with Hirschsprung＇s disease-associated enterocolitis

目的通过检测Th17细胞相关因子（IL-17、IL-23）在巨结肠相关性小肠结肠炎患儿外周血和肠黏膜中的表达，探讨Th17细胞相关因子与巨结肠相关小肠结肠炎发病的关系。方法取24例先天性巨结肠患儿（小肠结肠炎组11例，非肠炎组13例）的静脉血采用ELISA法检测血清中IL-17、IL-23的表达，对照组共19例，为腹股沟斜疝，隐睾，鞘膜积液的患儿。利用免疫组织化法检测19例巨结肠合并小肠结肠炎患儿的痉挛段、扩张段肠黏膜固有层中IL-17、IL-23的表达，对照组为4例先天性无肛结肠造瘘术患儿的结肠标本，比较表达的差异。结果小肠结肠炎组血清中IL-17水平为（133．23±113．85）pg／ml明显高于非肠炎组的（9．59±7．75）pg／ml及对照组的（17．96±20．27）pg／ml，差异有统计学意义（P〈0．05），非肠炎组与对照组间差异无统计学意义；小肠结肠肠炎组血清中IL-23水平为（607．29±213．00）pg／ml明显高于非肠炎组的（105．39±90．02）pg／ml及对照组的（214．08±227．90）pg／ml，差异有统计学意义（P〈O．05），非肠炎组与对照组间差异无统计学意义。免疫组化染色结果显示，在肠黏膜上皮细胞中，扩张段IL-17、IL-23阳性染色强度高于痉挛段和对照组，但二者差异无统计学意义。在肠黏膜固有层中，扩张段IL-17、IL-23阳性细胞百分数高于痉挛段和对照组，但两组间差异无统计学意义（F值分别为0．693、0．972，P〉0．05）。结论在巨结肠相关小肠结肠炎中，Th17细胞相关因子（IL-17、IL-23）在外周血中呈现高表达，提示Th17相关因子可能参与小肠结肠炎的发病过程，相关因子的测定有助于巨结肠相关小肠结肠炎的早期诊断。阻断IL-23／IL-17免疫通路有可能成为预防和治疗巨结肠相关性小肠结肠炎的有效途径。

Objective To explore the expressions of Th17-related cytokines （IL-17, IL-23） in peripheral blood and intestinal mucosa of children with Hirschsprung＇s disease-associated enterocolitis （HAEC） and examine the role of Th17-related cytokines in the pathogenesis of HAEC. Methods The clinical cases of Hirschsprung＇ s disease were confirmed by pathological findings postoperatively. They were divided into HAEC （n = 11） and non-HAEC （n = 13） groups. In the control group, there were 19 children including inguinal hernia, hydrocele and cryptorchidism. Serum levels of interleukin-17 （IL-17） and interleukin-23 （L-23） were measured by enzyme-linked immunosorbent assay （ELISA） for different groups. The expressions of IL-17 and IL-23 in intestinal mucosa were examined by immunohisochemistry. The specimens of spastic and dilated segment in 19 HAEC patients were examined while 4 cases of imperforated anus undergoing colostomy selected as control. Results In HAEC group, the serum level of IL-17 （133. 23 ± 113.85） pg/ml was significantly higher than that in non-HAEC （9. 59 ± 7. 75） pg/ml and control group （17. 96 ± 20. 27） pg/ml （P〈0. 05）. And no statistically significant difference existed between non-HAEC and control groups. In HAEC group, the serum level of IL-23 （607. 29 ± 213. 00） pg/ml was significantly higher than that in non-HAEC （105.39 ± 90. 02） pg/ml and control groups （214. 08 ± 227. 90） pg/ml （P〈0. 05）. And no statistically significant difference existed between non-HAEC and control groups. Immunohistochemical staining demonstrated that the positive cells of IL-17 and IL-23 in both intestinal epithelial cells and lamina propria of dilated segment was more intensely stained than that in spastic segment and control groups. However, there were no significant inter-group differences （F = 0. 693 ＆ 0. 972, P〉0. 05）. Conclusions In HAEC, Thl7-related cytokines （IL-17 ＆ IL-23） are up-regulated in peripheral blood. Thus Th17-related cytokines may be involved in the progression of HAEC. The assays of related cytokines aid an early diagnosis of HAEC. Hopefully a blockade of IL-23/IL-17 signal pathway may become an effective method of preventing and treating HAEC.