人参皂苷衍生物AD-1通过抑制NLRP3炎症小体活化改善TNBS诱导的小鼠急性IBD  

Ginsenoside derivative AD-1 improves TNBS-induced acute IBD in mice by inhibiting activation of NLRP3 inflammasome

作　　者：苏超 包阔 李佳威 黄胜男 韩园园 姜天意 朱婧尧 李芳芳(指导)[1] 金丹(指导)[1] SU Chao;BAO Kuo;LI Jiawei;HUANG Shengnan;HAN Yuanyuan;JIANG Tianyi;ZHU Jingyao;LI Fangfang;JIN Dan(Key Laboratory of Immunology and Pathogen Biology,Yanbian University School of Medicine,Yanji 133002,China)

机构地区：[1]延边大学医学院免疫学与病原生物学重点实验室,延吉133002

出　　处：《中国免疫学杂志》2023年第11期2305-2310,2317,共7页Chinese Journal of Immunology

基　　金：国家自然科学基金项目(81860288)。

摘　　要：目的:初步探讨人参皂苷衍生物AD-1对三硝基苯磺酸(TNBS)诱导的小鼠急性炎症性肠病(IBD)的影响及相关机制。方法:将6~8周龄的C57BL/6雄性小鼠随机分为正常对照组、乙醇对照组、模型组、治疗组和阳性对照组,后3组于造模前7 d采用1%TNBS乙醇溶液涂抹皮肤进行预敏化处理,造模日采用2.5%TNBS乙醇溶液灌肠建立小鼠急性IBD模型。AD-1和阳性对照药5-ASA于TNBS造模后第2天进行灌胃给药,连续灌胃4 d,第6天处死小鼠。取小鼠结肠,HE染色观察结肠组织的病理变化;RT-PCR和Western blot方法检测小鼠结肠组织的促炎细胞因子、紧密连接蛋白和NLRP3炎症小体的表达水平;ELISA法检测小鼠血清中IL-1β、IL-18水平。结果:AD-1能降低小鼠DAI评分,明显改善TNBS诱导的急性IBD小鼠结肠长度缩短的情况(P<0.01);治疗组小鼠结肠组织炎症病理明显改善,结肠组织促炎细胞因子IL-6、TNF-α、IL-1β、IL-18及NLRP3表达水平明显低于模型组(P<0.05或P<0.01);紧密连接蛋白的表达水平高于模型组(P<0.01)。结论:人参皂苷衍生物AD-1可能通过抑制NLRP3炎症小体活化缓解TNBS诱导的小鼠急性IBD。Objective:To investigate the effects of ginsenoside derivative AD-1 on acute inflammatory bowel disease(IBD)induced by TNBS in mice and the related mechanisms.Methods:Male C57BL/6 mice aged 6~8 weeks were randomly divided into normal control group,ethanol control group,model group,treatment group and positive control group.The latter three groups were presensitized with 1%TNBS ethanol solution skin smear seven days before modeling,and 2.5%TNBS ethanol solution enema was used on modeling day to establish acute IBD model of mice.AD-1 and positive control 5-ASA were given intragastric administration on the second day after TNBS modeling for four consecutive days,and mice were sacrificed on the sixth day.HE staining was used to observe the pathological changes of colon tissues.The expression levels of pro-inflammatory cytokines,tight junction protein and NLRP3 inflammasome in mouse colon tissues were detected by RT-PCR and Western blot.Serum levels of IL-1βand IL-18 were detected by ELISA.Results:AD-1 could decrease DAI score in mice.Moreover,AD-1 significantly improved colon length in TNBS-induced acute IBD mice(P<0.01);the inflammation and pathology of colon tissue in the treatment group were significantly improved.The expression levels of pro-inflammatory cytokines IL-6,TNF-α,IL-1β,IL-18 and NLRP3 in the treated group were significantly lower than those in the model group(P<0.05 or P<0.01);expression level of tight junction protein was higher than that of model group(P<0.01).Conclusion:Ginsenoside derivative AD-1 may alleviate TNBS-induced acute IBD in mice by inhibiting the activation of NLRP3 inflammasome.

关 键 词：人参皂苷衍生物AD-1 NLRP3 三硝基苯磺酸 炎症性肠病 

分 类 号：R574.62[医药卫生—消化系统]