基于IL-33/ST2信号通路的茯苓多糖调控溃疡性结肠炎大鼠肥大细胞活化的机制研究  

Study on mechanisms of Poria cocos polysaccharide regulating mast cell activation in rats with ulcerative colitis based on IL-33/ST2 signaling pathway

作　　者：梁桐尔 刘杨洋 王烜[1,3] LIANG Tong-Er;LIU Yang-Yang;WANG Xuan(Department of General Medicine,Affiliated Hospital of Southwest Medical University,Luzhou 646000,China)

机构地区：[1]西南医科大学附属医院全科医学科,泸州646000 [2]乐山市人民医院消化内科,乐山614000 [3]西南医科大学附属医院消化内科,泸州646000

出　　处：《中国免疫学杂志》2020年第11期1324-1329,1337,共7页Chinese Journal of Immunology

摘　　要：目的:探究基于IL-33/ST2信号通路的茯苓多糖调控溃疡性结肠炎(UC)大鼠肥大细胞(MC)活化的机制。方法:SPF级SD大鼠90只,15只大鼠为对照组,其余大鼠采用三硝基苯磺酸(TNBS)灌肠法建立UC模型,造模成功后大鼠分为模型组、茯苓多糖低剂量组(5 mg/kg)、中剂量组(100 mg/kg)、高剂量组(200 mg/kg)、柳氮磺胺吡啶组(SASP组)(300 g/kg),各组15只进行灌胃治疗,对照组、模型组每天灌胃生理盐水10 ml/kg,连续治疗14 d;治疗前后称量大鼠体质量,对大鼠进行疾病活动指数(DAI)评分,组织学损伤(TDI)评分,结肠黏膜损伤指数(CMDI)评分,HE染色观察病变部位炎症程度,甲苯胺蓝法检测MC形态、数目、脱颗粒率,免疫组化检测胰蛋白酶(TA)表达水平,ELISA法检测血清IL-33、IL-5、IL-13、IL-6、sST2的水平;Western blot检测结肠组织IL-33、ST2蛋白表达情况。结果:与对照组比较,模型组大鼠皮毛干枯、饮食量减少,黏膜腺体结构排列紊乱,炎症细胞浸润,MC数目、TA水平及IL-33、IL-5、IL-13、IL-6、sST2的水平升高(P<0.05);与模型组比较,茯苓多糖组和SASP组大鼠饮食量增加,精神状态改善,黏膜损伤及炎症细胞减轻,MC数目、TA水平、IL-33、IL-5、IL-13、IL-6、sST2的水平显著降低,尤以茯苓多糖高剂量组和SASP组治疗效果最为显著(P<0.05)。结论:MC活化在UC发病机制中发挥重要作用,中药茯苓多糖和SASP对UC均具有明显的治疗作用,茯苓多糖可通过抑制IL-33/ST2信号通路的激活,减少MC活化,抑制炎症因子的表达,降低结肠炎症浸润程度。Objective:To explore the mechanism of Poria cocos polysaccharide regulating mast cell(MC)activation in ulcerative colitis(UC)rats based on IL-33/ST2 signaling pathway.Methods:15 rats of 90 SPF SD rats were used as control group,and the other rats were treated with TNBS enema to establish UC model.After successful modeling,the rats were divided into model group,Poria cocos polysaccharide low dose group(5 mg/kg),middle dose group(100 mg/kg),high dose group(200 mg/kg)and sulfasalazine group(SASP group)(300 g/kg),all the groups(n=15)were given intragastric administration,and the control group and model group were given 10 ml/kg saline daily for 14 days.The rats were weighed before and after treatment,and were scored with disease activity index(DAI),histological injury(TDI)score,colonic mucosal injury index(CMDI)score,the HE staining was used to observe the degree of inflammation,the morphology,number and degranulation rate of MC were determined by toluidine blue method,the expression of trypsin(TA)was detected by immunohistochemistry,levels of serum IL-33,IL-5,IL-13,IL-6 and sST2 were detected by ELISA.Western blot was used to detect the expressions of IL-33 and ST2 in colon tissue.Results:Compared with the control group,the fur of rats in the model group was dry,the dietary intake reduced,the structure of mucosal glands was disordered,the number of MC,levels of TA,IL-33,IL-5,IL-13,IL-6 and sST2 increased(P<0.05).Compared with the model group,the dietary intake of rats in the Poria cocos polysaccharide group and SASP group increased,mental state improved,mucosal lesions and inflammatory cells were alleviated,and the number of MC,levels of TA,IL-33,IL-5,IL-13,IL-6 and sST2 decreased significantly,especially in the Poria cocos polysaccharide high-dose group and SASP group(P<0.05).Conclusion:MC activation plays an important role in the pathogenesis of UC.Poria cocos polysaccharide and SASP have obvious therapeutic effects on UC.Poria cocos polysaccharide can inhibit the activation of IL-33/ST2 signaling pathway,reduce M

关 键 词：IL-33/ST2信号通路 茯苓多糖 溃疡性结肠炎 肥大细胞 

分 类 号：R285.5[医药卫生—中药学]