丁酸钠下调IRAK1改善肠易激综合征内脏高敏感  

Sodium butyrate ameliorates visceral hypersensitivity by down-regulating IRAK1 in irritable bowel syndrome

作　　者：李竹青 张文雪[1] 李理想[1] 王鹏[1] 于岩波[1] 左秀丽[1] 李延青[1] LI Zhuqing;ZHANG Wenxue;LI Lixiang;WANG Peng;YU Yanbo;ZUO Xiuli;LI Yanqing(Department of Gastroenterology,Qilu Hospital of Shandong University,Jinan 250012,Shandong,China)

机构地区：[1]山东大学齐鲁医院消化内科,山东济南250012

出　　处：《山东大学学报（医学版）》2018年第9期23-28,共6页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金(81670489)

摘　　要：目的探究丁酸钠改善肠易激综合征(IBS)内脏高敏感性机制。方法纳入27例腹泻型肠易激综合征(IBS-D)患者及22例对照共49例参与者,免疫组化检测肠上皮IRAK1蛋白表达量,Spearman秩和检验分析IRAK1蛋白表达与腹痛程度和频率评分相关性。2,4,6-三硝基苯磺酸灌肠建立IBS疾病动物模型,丁酸钠灌肠干预,结肠扩张实验观察内脏敏感性变化,ELISA检测结肠IRAK1蛋白表达水平,Spearman秩和检验分析动物结肠IRAK1表达与内脏疼痛阈值相关性。以IL-33、丁酸钠干预HT-29细胞,Western blotting观察IRAK1蛋白表达变化。结果 IBS-D患者结肠上皮IRAK1蛋白表达高于对照组,结肠上皮IRAK1表达水平与腹痛程度评分呈正相关(r=0.676,P<0.001),与腹痛频率评分呈正相关(r=0.725,P<0.001)。丁酸钠干预可降低IBS动物结肠IRAK1蛋白表达、提高内脏疼痛阈值,动物结肠IRAK1蛋白表达与内脏疼痛阈值呈负相关(r=-0.655,P<0.001)。IL-33可使细胞IRAK1蛋白表达上调,丁酸钠预处理可减弱此效应。结论丁酸钠可能通过下调IRAK1蛋白表达水平改善IBS内脏高敏感性。Objective To investigate the role and mechanism of sodium butyrate in the treatment of irritable bowel syndrome（ IBS）. Methods A total of 49 participants comprised of 27 diarrhea-dominant IBS（ IBS-D） patients and 22 controls were included. The protein expression of interleukin-1 receptor-associated kinase 1（ IRAK1） in the colonic epithelium was detected with immunohistochemistry staining. The relationship between the IRAK1 protein expression and abdominal pain scores was analyzed with Spearman correlation analysis. After the animal models of IBS were established by 2,4,6-trinitrobenzene sulphonic acid enema,they were treated with sodium butyrate enema. The visceral hypersensitivity was observed using colorectal distension. The IRAK1 expression was determined with enzyme linked immunosorbent assay（ ELISA）. The relationship between IRAK1 expression and visceral pain threshold was analyzed with Spearman correlation analysis. After the HT-29 cell lines were treated with IL-33 and sodium butyrate,the IRAK1 protein expression was detected with Western blotting. Results Patients with IBS-D showed a higher expression of IRAK1 in colonic epithelium than the controls and IRAK1 expression was positively correlated with abdominal pain severity scores（ r = 0. 676,P〈0. 001） and frequency scores（ r = 0. 725,P〈0. 001）. IBS animal models treated with sodium butyrate enema exhibited a lower expression of IRAK1 in the colon tissues and a higher visceral pain threshold.The IRAK1 protein expression was negatively correlated with pain threshold（ r =-0. 655,P〈0. 001）. IL-33 stimulation could upregulate the protein expression of IRAK1 in HT-29 cell lines,while sodium butyrate pretreatment could diminish the effect. Conclusion Sodium butyrate may ameliorate visceral hypersensitivity in irritable bowel syndrome by down-regulating the protein expression of IRAK1.

关 键 词：丁酸钠 白介素-1受体相关激酶1 肠易激综合征 内脏高敏感 

分 类 号：R574[医药卫生—消化系统]