肠易激综合征模型大鼠血清胰高糖素样肽-1及结肠组织中其受体的变化  

Changes of serum glucagon-like peptide-1 and colonic glucagon-like peptide-1 receptor in rat models of irritable bowel syndrome subtypes

作　　者：李正阳[1] 陈燕[1] 林琳[1] 王美峰[1] 郝波[1] 张红杰[1] 

机构地区：[1]南京医科大学第一附属医院消化科,210029

出　　处：《中华消化杂志》2012年第4期249-255,共7页Chinese Journal of Digestion

基　　金：基金项目：国家自然科学基金面上项目[30771039（BA07）]

摘　　要：目的观察肠易激综合征（IBS）不同亚型模型大鼠血清胰高糖素样肽（GLP）-1及结肠组织中GLP-1受体的变化，初步探讨GLP-1及其受体在IBS发病中的作用。方法40只雄性SD大鼠均分为腹泻型IBS（D-IBS）模型组、灌肠对照组、便秘型IBS（C—IBS）模型组、灌胃对照组及空白对照组。乙酸加束缚应激法制备D-IBS模型，冰水灌胃法制备C-IBS模型。观察大鼠粪便变化，检测粪便重量、粪便含水量及大鼠小肠推进率，给予结直肠扩张（CRD）刺激，记录腹外斜肌放电活动（EMG），评价模型大鼠的内脏敏感性。酶联免疫法测定各组大鼠血清中活性GLP-1的含量。免疫组织化学法、实时定量PCR法及Western印迹法检测各组大鼠近端结肠及远端结肠组织中GLP-1受体的分布和表达。结果与各自的对照组及空白对照组相比，D-IBS模型组大鼠粪便湿重、粪便含水量及小肠推进率均上升（P〈0．05）；C-IBS模型组粪便湿重、粪便含水量及小肠推进率均降低（P〈0．05）。在压力为20、40及60mmHg（1mmHg—0．133kPa）的结直肠扩张刺激下各模型组大鼠腹外斜肌放电幅值均较各对照组明显增加，且D-IBS模型组高于C-IBS模型组（P〈0．05）。C-IBS模型组血清中活性GLP-1的水平高于D-IBS模型组（P〈0．05），IBS模型组和对照组之间差异无统计学意义。GLP-1受体主要分布在结肠黏膜组织、环肌层及肌间神经丛中。C-IBS模型组结肠组织中GLP-1受体mRNA及蛋白表达量显著高于灌胃对照组，D-IBS模型组结肠组织中表达量低于灌肠对照组（P〈0．05）。结论不同亚型IBS结肠组织中GLP-1受体的表达水平不同，血清GLP-1水平也不同，提示GLP-1及其受体的改变可能与IBS不同亚型的发生有关。Objective To investigate the changes of serum glucagon-like peptide （GLP）-1 and colonic GLP-1 receptor in rat models of irritable bowel syndrome （IBS） subtypes and to explore the role of GLP-1 and its receptor in the pathogenesis of IBS. Methods Forty male SD rats were equally divided into D-IBS group, enema control group （D-IBS control group）, C-IBS group, gavage control group （C-IBS control group） and blank control group. The D-IBS model was created by the method of acetic acid and restraint stress. The C-IBS model was created by ice water gavage. Changes in rat feces were observed, the weight and water content of feces and the advance rate of rat small intestinal transit were detected. The colorectum was given distension （CRD） stimulation, the electrical activity of external oblique （EMG） was recorded and the visceral sensitivity of rats model was evaluated. The content of active GLP-1 in serum was detected by ELISA in each group. The distribution and expression of GLP-1 receptor in rat proximal colon and distal colon tissue of each group were detected by immunohistochemistry, real-time PCR and Western blot. Results Compared with respective control group and blank control group, the wet weight and water content of feces and the advance rate of rat small intestinal transit all increased （P〈0.05） in D-IBS group . However, the wet weight and water content of feces and the advance rate of rat small intestinal transit all decreased （P〈0.05） in C- IBS group. At the pressure of 20, 40 and 60 mm Hg （1 mm Hg=0. 133 kPa） colorectal distension stimulation, the amplitude of the external oblique discharge significantly increased in model groups compared with their control groups, and which was higher in D-IBS group than that of C-IBS group （P〈0.05）. The level of active GLP -1 in serum was higher in C-IBS group than in D-IBS group （P〈 0.05）. There was no significant difference between IBS group and control group. GLP-1 receptors mainly distributed in the colon mucosa, circ

关 键 词：肠易激综合征 胰高血糖素样肽1 受体 胰高血糖素 内脏敏感性 结肠 疾病模 型 动物 

分 类 号：R574.62[医药卫生—消化系统]