木兰花碱对溃疡性结肠炎模型大鼠的治疗作用及其机制  

Therapeutic Effect and Its Mechanism of Magnoflorine on the Rats with Ulcerative Colitis

作　　者：徐志红[1] 陈磊垚[1] 许立[2] 徐德荣 XU Zhihong;CHEN Leiyao;XU Li;XU Derong(Department of Pharmacy,Affliated Hospital of Nanjing Integrated Traditional Chinese and Western Medicine,Nanjing University of Chinese Medicine,Nanjing 210014,China;Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica,Nanjing University of Chinese Medicine,Nanjing 210046,China)

机构地区：[1]南京中医药大学附属南京市中西医结合医院药学部,南京210014 [2]南京中医药大学江苏省中药药效与安全性评价重点实验室,南京210046

出　　处：《医药导报》2023年第1期16-23,共8页Herald of Medicine

基　　金：南京市医学科技发展项目(QYK11148)。

摘　　要：目的观察木兰花碱对溃疡性结肠炎(UC)大鼠核因子(NF)-κB信号通路和Nod样受体家族含pyrin结构域蛋白3(NLRP3)炎性小体活性的影响,探讨木兰花碱对UC的作用及其机制。方法SD大鼠60只,随机分为正常对照组、模型对照组、5-氨基水杨酸组(100 mg·kg^(-1))和木兰花碱小、中、大剂量组(25,50,100 mg·kg^(-1)),每组10只。正常对照组灌胃纯净水,其余5组灌胃给予相应药物,每天1次,连续10 d。给药结束后,取结肠组织,经苏木精-伊红(HE)染色后观察组织结构;酶联免疫吸附实验(ELISA)法检测结肠组织中促炎症细胞因子白细胞介素(IL)-1β、IL-18和肿瘤坏死因子(TNF)-α含量;免疫荧光法检测CD11b^(+)巨噬细胞数量;蛋白免疫印迹法和免疫组织化学法检测木兰花碱对NF-κB/NLRP3炎性小体信号通路相关蛋白的影响。结果木兰花碱可降低UC大鼠的疾病活动指数、病理组织学评分、促炎症细胞因子表达水平和结肠组织中CD11b^(+)巨噬细胞数量。木兰花碱降低UC大鼠结肠组织中p-IκBα、p-IKKβ和细胞核p-NF-κB p65蛋白表达水平,增加细胞质p-NF-κB p65蛋白表达水平。木兰花碱明显降低NLRP3炎性小体相关蛋白(NLRP3、ASC、cleaved caspase-1)的表达水平。结论木兰花碱对UC模型大鼠有明显治疗作用,其机制可能与调控NF-κB/NLRP3炎性小体信号通路密切相关。Objective To observe the effect of magnoflorine on NF-κB signaling pathway and NLRP3 inflammasome activity,and to explore the possible mechanism of magnoflorine on ulcerative colitis in rats.Methods Sixty SD rats were randomly divided into normal control group,model control group,5-aminosalicylic acid group(100 mg·kg^(-1))and magnoflorine low-dose,medium-dose and high-dose groups(25,50,100 mg·kg^(-1)),with 10 rats in each group.The normal control group was given purified water by gavage,and the other 5 groups were given corresponding drugs by gavage,once a day for 10 days.After the administration,the colonic tissue of rats was collected,stained by hematoxylin and eosin(HE)and observed under microscope.The contents of pro-inflammatory cytokines(IL-1β,IL-18 and TNF-α)in colon tissues were detected by the ELISA method.The number of CD11b^(+)macrophages was detected by the immunofluorescence method.The effect of magnoflorine on the express of NF-κB/NLRP3 inflammasome signaling pathway related protein was detected by western blotting and immunohistochemistry method.Results Magnoflorine could reduce the disease activity index,histopathological score,the expression levels of pro-inflammatory cytokines and the number of CD11b^(+)macrophages in colon tissue of UC rats.Magnoflorine decreased the expressions of p-IκBαand p-IKKβprotein in the colon tissue of UC rats and p-NF-κB p65 protein in the cell nucleus,and increased the expression of p-NF-κB p65 protein in the cytoplasm.Magnoflorine significantly decreased the levels of NLRP3 inflammasome-related proteins(NLRP3,ASC,Cleaved caspase-1).Conclusion Magnoflorine has an obvious therapeutic effect on the rats with UC,the mechanism of which may be closely related to the regulation of NF-κB/NLRP3 inflammasome signaling pathway.

关 键 词：木兰花碱 溃疡性结肠炎 核因子-ΚB 

分 类 号：R282.71[医药卫生—中药学] R285[医药卫生—中医学]