基于调节炎症因子与上调肠道紧密连接蛋白研究健脾化滞丸治疗小鼠溃疡性结肠炎  

Therapeutic Effect of Jianpihuazhi(健脾化滞)Pills on Ulcerative Colitis in Mice Based on the Regulation of Inflammatory Factors and Intestinal Tight Junction Protein

作　　者：陈刚[1] 顾玮 吴育[1] 张硕 陈钟钰 王澄 蒋晟昰 CHEN Gang;GU Wei;WU Yu;ZHANG Shuo;CHEN Zhongyu;WANG Cheng;JIANG Shengshi(Nantong Hospital of Traditional Chinese Medicine,Nantong 226000;Nanjing University of Chinese Medicine,Nanjing 210023;Nantong Health College of Jiangsu Province,Nantong 226000)

机构地区：[1]南通市中医院,南通226000 [2]南京中医药大学,南京210023 [3]江苏省南通卫生高等职业技术学校,南通226000

出　　处：《中药药理与临床》2024年第11期29-34,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：2021年南通市科技项目(编号:JC2021097);2021年南通市药学会-常州四药医院药学基金科研项目(编号:ntyx2102);中药创新团队项目;江苏省中药骨干人才高级研修项目。

摘　　要：目的:研究健脾化滞丸对DSS诱导的溃疡性结肠炎小鼠的治疗作用,并探讨其初步的作用机制。方法:建立溃疡性结肠炎小鼠模型并随机分为模型对照组、健脾化滞丸50、100、200 mg/kg组、奥沙拉嗪200 mg/kg组,另取8只小鼠记为正常对照组。各组灌胃相应药物或生理盐水。观察小鼠活动状态以及粪便性状;测定小鼠的疾病活动指数(DAI)、小鼠结肠长度、脏器指数、结肠黏膜损伤指数(CMDI)及观察结肠病理变化;对结肠上皮细胞和炎性细胞浸润进行病理组织学(HS)评分;通过免疫组化法检测紧密连接蛋白Claudin-1、Occludin的表达;ELISA法测定结肠组织中的肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、IL-10、髓过氧化物酶(MPO)、基质金属蛋白酶(MMP-2)、一氧化氮合酶(INOS)的含量。结果:给药7 d后,造模组小鼠精神状态有所好转,腹泻、便下粘液脓血的症状明显改善,小鼠体质量增加。奥沙拉嗪组和健脾化滞丸各组结肠粘膜组织病理损伤减轻。与正常对照组相比,模型对照组小鼠DAI评分、CMDI评分、HS评分、结肠组织中的TNF-α、IL-6炎症因子含量和MPO、MMP-2、INOS酶的含量显著升高,小鼠结肠组织中Claudin-1和Occludin的蛋白表达、IL-10含量显著降低(P<0.01);与模型对照组相比,奥沙拉嗪组和健脾化滞丸各组小鼠CMDI、HS评分降低、结肠组织中的TNF-α、MPO、IL-6、MMP-2、INOS促炎因子的含量明显降低(P<0.05),IL-10含量升高,奥沙拉嗪组和健脾化滞丸100、200 mg/kg组小鼠结肠组织Claudin-1、Occludin蛋白表达升高(P<0.05)。结论:健脾化滞丸对DSS诱导的小鼠溃疡性结肠炎有治疗作用,机制可能与改善溃疡性结肠炎小鼠的相关炎症因子及降低肠道通透性有关。Objective:To investigate the therapeutic effect of Jianpihuazhi Pills on DSS-induced ulcerative colitis(UC)in mice and to explore its preliminary mechanism of action.Methods:A mouse model of UC was established and UC model mice were randomly divided into a model control group,Jianpihuazhi Pills groups at doses of 50,100,and 200 mg/kg,and a 200 mg/kg olsalazine group.Another 8 mice were assigned to the normal control group.Each group was administered the corresponding drugs or saline by gavage.The activity and fecal characteristics of the mice were observed.Disease activity index(DAI),colon length,organ index,colonic mucosal damage index(CMDI),and histopathological changes in the colon were assessed.Histopathological(HS)scoring was conducted for colonic epithelial cells and inflammatory cell infiltration.Immunohistochemistry was used to detect the expression of tight junction proteins claudin-1 and occludin.Levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-10,myeloperoxidase(MPO),matrix metalloproteinase-2(MMP-2),and inducible nitric oxide synthase(iNOS)in colon tissue were measured.Results:After 7 days of treatment,the general condition of the model mice improved,with significant alleviation of diarrhea and mucus,pus,and blood in the stool.The body weight of the mice gradually recovered.The olsalazine group and the Jianpihuazhi Pills groups reduced pathological damage to the colonic mucosa.Compared with the normal control group,the model control group showed significantly higher DAI scores,CMDI scores,HS scores,levels of inflammatory factors TNF-α and IL-6,and contents of MPO,MMP-2,and iNOS in the colon tissue,while the expression levels of claudin-1,occludin proteins,and IL-10 were significantly lower(P<0.01).Compared with the model control group,the olsalazine group and Jianpihuazhi Pills groups showed improvements in CMDI and HS scores,and reduced levels of TNF-α,MPO,IL-6,MMP-2,and iNOS in the colon tissue(P<0.05),while the levels of anti-inflammatory factor IL-10 were elevated.The olsalazine

关 键 词：健脾化滞丸 溃疡性结肠炎 炎症因子 紧密连接蛋白 紧密连接蛋白 

分 类 号：R28[医药卫生—中药学]