摘要
目的探讨大麻素受体CB2通过调节巨噬细胞极化改善溃疡性结肠炎(UC)的免疫学机制,为新药的研发和疾病的治疗提供新的思路。方法人UC标本用CD68免疫组织化学染色标记巨噬细胞;雄性ICR小鼠使用葡聚糖硫酸钠DSS制备成UC模型,用CB2受体激动剂JWH133干预后,观察小鼠体质量、记录UC活动指数DAI(腹泻和便血程度)并收集肠道组织,应用HE染色、Real-time PCR等技术,分析炎症程度并测定肠道巨噬细胞的极性;体外培养外周血来源的巨噬细胞(PBM),用LPS和IL-4分别诱导为M1和M2型PBM,JWH133干预后,用Real-time PCR测定PBM的极性变化。结果UC患者的结肠组织中存在大量PBM;JWH133使UC小鼠结肠中PBM的极性从M1型向M2型转化,同时改善小鼠体质量下降和DAI指数,肠道炎症程度明显减轻;体外,JWH133使M1-PBM的M1标志物水平下降(TNF-α、IL-1β和IL-12),并提高M2-PBM的Arg1、Mrc2和Mgl1的水平。结论CB2受体通过调节PBM向M2型转化来改善UC。
Objective To investigate the immunological mechanism of cannabinoid receptor CB2 in ulcerative colitis(UC)by regulating macrophage polarization so as to provide new ideas for the development of new drugs and treatment of the disease.Methods Human UC specimens were immunohistochemically stained with macrophage mark CD68.Male ICR mice were made into ulcerative colitis model by dextran sulfate sodium DSS.After treatment with CB2 receptor agonist JWH133,the weight of the mice and the inflammatory activity indexes(DAI)(diarrhea and bloody stool)of UC were recorded,and the intestinal tissues were collected.The degree of inflammation and polarity of macrophages of intestinal tract were analyzed with HE staining and Real-time PCR.Peripheral blood-derived macrophages(PBMs)were cultured in vitro and induced into M1 and M2 macrophages by LPS and IL-4,respectively.After intervention with JWH133,the polarity of macrophages was measured by Real-time PCR.Results There were a large number of macrophages in the colonic tissues of UC patients.JWH133 transformed the polarity of macrophages from M1 to M2 in UC mice,improved the weight loss and DAI of mice,and significantly decreased the degree of intestinal inflammation.In vitro,JWH133 decreased the level of M1-PBM markers(TNF-α,IL-1βand IL-12)and elevated Arg1,Mrc2 and Mgl1 of M2-PBM.Conclusion CB2 receptor can improve UC by regulating macrophage transformation to M2 type.
作者
麦平
肖晓辉
付应明
张丽萍
雷维商
马欣
MAI Ping;XIAO Xiaohui;FU Yingming;ZHANG Liping;LEI Weishang;MA Xin(Department of Gastroenterology,Gansu Provincial Hospital,Lanzhou 730000;Department of Pneumology,Gansu Provincial Hospital,Lanzhou 730000;Department of Internal Medicine,People's Hospital of Wushan County,Tianshui 741300;Department of Gastroenterology,Gansu Second Provincial Hospital,Lanzhou 730000,China)
出处
《西安交通大学学报（医学版）》
CAS
CSCD
北大核心
2020年第2期210-215,共6页
Journal of Xi’an Jiaotong University（Medical Sciences）
基金
国家自然科学基金资助项目(No.81560093)
甘肃省人民医院基金资助项目(No.16GSSY1-8)~~
关键词
溃疡性结肠炎
巨噬细胞极化
大麻素受体2
ulcerative colitis
macrophage polarization
cannabinoid receptor 2
