华蟾素对溃疡性结肠炎大鼠的作用及机制  

Effect and the mechanism of Huachansu on ulcerative colitis in rats

作　　者：李时超 殷佩浩[1,3] 陈腾 陈超[1,3] 李五生 王杰[1,3] LI Shi-chao;YIN Pei-hao;CHEN Teng;CHEN Chao;LI Wu-sheng;WANG Jie(Department of General Surgery,PuIud Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200062,China;Department of Anorectal,Traditional Chinese Medicine Hospital Affiliated to Southwest Medical University,Luzhou 646000,Sichuan Province,China;Department of General Surgery,Putuo Center Clinical College,Anhui Medical University,Shanghai 200062,China)

机构地区：[1]上海中医药大学附属普陀医院普外科,上海200062 [2]西南医科大学附属中医医院肛肠科,四川泸州646000 [3]安徽医科大学普陀中心临床学院普外科,上海200062

出　　处：《中国临床药理学杂志》2021年第21期2924-2928,共5页The Chinese Journal of Clinical Pharmacology

基　　金：上海市医学重点专科建设计划基金资助项目(ZK2019B18);上海市普陀区特色专病-大肠癌项目基金资助项目(2019tszb01);上海市普陀区临床重点专科基金资助项目(2016ptzk01)。

摘　　要：目的研究华蟾素对溃疡性结肠炎(UC)大鼠的作用及其机制。方法用2,4,6-三硝基苯磺酸(TNBS)结肠灌注建立UC大鼠模型。按照大鼠体重随机分为对照组、模型组、阳性对照组、华蟾素低剂量组(HCS-L)、华蟾素高剂量组(HCS-H),每组6只。对照组、模型组予以生理盐水灌肠,阳性对照组给予美沙拉嗪灌肠液1.5 g·kg^(-1)灌肠,HCS-L、HCS-H分别予以华蟾素200、400 mg·kg^(-1)灌肠,每日1次,连续14 d。用疾病活动指数(DAI)、结肠黏膜损伤指数(CMDI)进行评分,用苏木素-伊红(HE)染色观察结肠病理变化,用酶联免疫吸附(ELISA)法检测血清中炎性因子水平,用免疫组化法检测结肠组织中NOD样受体蛋白3(NLRP3)、胱天蛋白酶-1(caspase-1)、咬合蛋白(Occludin)、带状闭合蛋白(ZO-1)的表达情况。结果对照组、模型组、阳性对照组、HCS-L、HCS-H的DAI评分分别为0.11±0.27,2.44±0.54,1.22±0.78,1.33±0.73,1.06±0.61;上述5组的CMDI评分分别为0.17±0.41,2.83±1.17,1.00±0.89,1.33±0.52,0.83±0.75;与正常组比较,模型组DAI评分、CMDI评分均显著升高,与模型组比较,阳性对照组、HCS-L、HCS-H的DAI评分、CMDI评分均显著降低(均P<0.05)。与正常组比较,模型组血清中白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18)、肿瘤坏死因子-α(TNF-α)均显著升高,与模型组比较,阳性对照组、HCS-L、HCS-H血清中IL-1β、IL-18、TNF-α均显著降低(均P<0.01);与正常组比较,模型组结肠组织中NLRP3、caspase-1的平均光密度值均显著升高,Occludin、ZO-1的平均光密度值均显著降低(均P<0.01),与模型组比较,阳性对照组、HCS-L、HCS-H结肠组织中NLRP3、casepase-1的平均光密度值均显著降低,Occludin、ZO-1的平均光密度值均显著升高(均P<0.01)。结论华蟾素可明显缓解UC大鼠症状,改善UC大鼠肠黏膜病变,其机制可能与抑制NLRP3的过度激活、降低炎症反应、增强黏膜屏障的完整性有关。Objective To investigate the effect and underlying mechanism of Huachansu on ulcerative colitis(UC)in rats.Methods UC rat model was induced by 2,4,6-trinitrobenzene sulfonic acid(TNBS)intra-colonic adminisrataion.According to the weight of the rats,they were randomly divided into five groups:control group,model group,positive control group,Huachansu low-dose group(HCS-L),and Huachansu high-dose group(HCS-H),with 6 rats in each group.The control group and model group were given normal saline via enema administration,and the positive control group was given mesalazine enema 1.5 g·kg^(-1),HCS-L and HCS-H were given Huachansu 200 and 400 mg·kg^(-1).All the drugs were administered once a day for consecutive 14 days.The disease activity index(DAI)and colonic mucosal injury index(CMDI)were evaluated.Hematoxylin-eosin(HE)staining was used to observe colon pathological changes.Serum inflammatory factor levels were detected by enzyme-linked immunosorbent assay(ELISA).Immunohistochemistry was used to detect the expression of NOD-like receptor protein 3(NLRP3),Cysteinyl aspartate specific proteinase-1(caspase-1),Occludin,and Zonula occludens-1(ZO-1)in colon tissue.Results The DAI scores of the control group,model group,positive control group,HCS-L,and HCS-H were 0.11±0.27,2.44±0.54,1.22±0.78,1.33±0.73,1.06±0.61,respectively;the CMDI scores of the above five groups were0.17±0.41,2.83±1.17,1.00±0.89,1.33±0.52,0.83±0.75;compared with control group,the DAI score and CMDI score of model group were significantly increased(P<0.01);compared with model group,the DAI score and CMDI score of positive control group,HCS-L and HCS-H were significantly decreased(all P<0.05).Compared with control group,the serum levels of interleukin-1β(IL-1β),interleukin-18(IL-18)and tumor necrosis factor-α(TNF-α)in model group were significantly increased;compared with model group,the serum levels of IL-1β,IL-18,and TNF-αin positive control group,HCS-L,and HCS-H were significantly reduced(all P<0.01).Compared with control group,the avera

关 键 词：溃疡性结肠炎 华蟾素 NOD样受体蛋白3 紧密连接蛋白 

分 类 号：R28[医药卫生—中药学]