胰高血糖素样肽-2对TNBS诱导的克罗恩病大鼠肠黏膜组织损伤及Th1/Th2细胞免疫平衡的影响  

Effects of glucagon-like peptide-2 on TNBS-induced intestinal mucosal tissue injury and Th1/Th2 cell immune balance in Crohn's disease

作　　者：陈卿奇 庞莉 冯彩团 李文妍 程芃 CHEN Qingqi;PANG Li;FENG Caituan;LI Wenyan;CHENG Peng(Department of Gastroenterology,Western Central Hospital of Hainan,Danzhou 571799,China)

机构地区：[1]海南西部中心医院消化科,儋州571799

出　　处：《中国免疫学杂志》2025年第4期867-872,共6页Chinese Journal of Immunology

基　　金：海南省基础与应用基础研究计划(省自然科学基金)立项项目(821RC733);海南省卫生健康行业科研项目(20A200397)。

摘　　要：目的:探究胰高血糖素样肽-2(GLP-2)对三硝基苯磺酸(TNBS)诱导的大鼠克罗恩病(CD)肠黏膜组织损伤及辅助性T细胞1/辅助性T细胞2(Th1/Th2)平衡的影响。方法:将40只大鼠随机分为对照组、CD组、治疗(CD+GLP-2)组、阳性对照[CD+柳氮磺吡啶(SASP)]组,每组10只,除对照组外,其余3组大鼠均采用TNBS诱导建立CD模型并给予相应处理后,评估结肠组织大体形态损伤指数(CMDI),HE染色观察肠黏膜组织病理学变化,TUNEL染色检测结肠组织细胞凋亡,ELISA测定血清IFN-γ、TNF-α、IL-12、IL-4及IL-10水平,免疫组化染色法检测结肠组织内IFN-γ与IL-4表达,流式细胞术检测脾脏中Th1/Th2。结果:与CD组比较,CD+GLP-2组和CD+SASP组大鼠CMDI显著降低(P均<0.001),肠黏膜损伤得到改善,结肠组织中TUNEL阳性率显著降低(P均<0.001),血清IFN-γ、TNF-α、IL-12含量显著减少(P均<0.001),血清IL-4、IL-10含量显著增加(P均<0.001),结肠组织IFN-γ表达显著降低且IL-4表达显著升高(P均<0.001),Th1细胞比例显著减少、Th2细胞比例显著增加(P均<0.001),Th1/Th2也显著降低(P均<0.001)。结论:GLP-2能够有效改善TNBS诱导的CD大鼠肠黏膜损伤,其机制可能与调节Th1/Th2细胞免疫平衡、抑制炎症反应、减少细胞凋亡有关。Objective:To investigate the effect of glucagon like peptide-2(GLP-2)on 2,4,6-trinitrobenzenesulfonic acid(TNBS)induced intestinal mucosal tissue damage and the effects of helper T cell 1/helper T cell 2(Th1/Th2)balance in rats with Crohn's disease(CD).Methods:Forty rats were randomly divided into control group,CD group,treatment(CD+GLP-2)group and positive control[CD+sulfasalazine(SASP)]group,with 10 rats in each group.TNBS induced CD model was established and the rats in the other 3 groups were given corresponding treatment.After completion,colon macroscopic damage index(CMDI)was evaluated,HE staining was used to observe the histopathological changes of intestinal mucosa,TUNEL staining was used to detect apoptosis of colonic tissue cells,ELISA was used to determine serum IFN-γ,TNF-α,IL-12,IL-4 and IL-10,immunohistochemical staining was used to detect the expressions of IFN-γand IL-4 in colon tissues,flow cytometry was used to determine the proportion of Th1/Th2 in spleen.Results:Compared with CD group,CMDI in CD+GLP-2 group and CD+SASP group were significantly decreased(P all<0.001),intestinal mucosal damage was improved,the positive rate of TUNEL in colon tissue was significantly decreased(P all<0.001),the contents of IFN-γ,TNF-αand IL-12 in serum were significantly decreased(P all<0.001),the contents of IL-4 and IL-10 in serum were significantly increased(P all<0.001),the expression of IFN-γin colon tissue was significantly decreased and the expression of IL-4 was significantly increased(P all<0.001),the proportion of Th1 cells was significantly decreased while the proportion of Th2 cells was significantly increased(P all<0.001),Th1/Th2 also decreased significantly(P all<0.001).Conclusion:GLP-2 can effectively improve the intestinal mucosal injury of CD rats induced by TNBS,and the mechanism may be related to regulating the immune balance of Th1/Th2 cells,inhibiting inflammatory response and reducing cell apoptosis.

关 键 词：克罗恩病 胰高血糖素样肽-2 肠黏膜损伤 辅助性T细胞1/辅助性T细胞2平衡 

分 类 号：R285.5[医药卫生—中药学]