丹参酮IIA通过调控中性粒细胞活性减轻DSS诱导的小鼠急性结肠炎  

Tanshinone IIA protects against dextran sulfate sodium(DSS)-induced colitis by neutrophil modulation in mice

作　　者：周艳[1] 李安[2] 朱钧[2] 

机构地区：[1]首都医科大学附属北京朝阳医院医学研究中心,北京100020 [2]首都医科大学附属北京朝阳医院职业病与中毒医学科

出　　处：《毒理学杂志》2017年第2期84-87,88,共5页Journal of Toxicology

基　　金：北京市自然科学基金(7142064)

摘　　要：目的观察丹参酮IIA对葡聚糖硫酸钠(DSS)诱导的小鼠实验性结肠炎是否有干预效果以及对结肠黏膜中性粒细胞浸润和活化的影响,旨在探讨丹参酮IIA治疗结肠炎的作用机制。方法随机将30只C57BL/6小鼠分为正常对照组、DSS组和DSS+丹参酮IIA干预组,每组10只动物;其中模型组给予3%DSS溶液喂饲7 d,干预组小鼠在给予3%DSS溶液喂饲的同时给予丹参酮IIA(200 mg/kg)腹腔注射,1次/d;期间对小鼠疾病活动指数(DAI)进行评分。染毒7 d后处死小鼠,取结肠组织进行病理学检查;采用异硫氰酸荧光素标记葡聚糖(FITC-dextran)法检测小鼠肠黏膜通透性;采用免疫荧光染色方法检测结肠组织Ly6G的表达,并检测MPO活性和炎症因子的水平。结果和正常对照组相比,DSS组小鼠第7天时出现体重减轻、便血和腹泻等症状,DAI显著增高。丹参酮IIA干预明显减轻小鼠结肠炎性损伤,表现为干预组小鼠DAI低于DSS组,差异有统计学意义(P<0.05);干预组小鼠结肠组织病理损伤显著减轻,肠黏膜穿透性亦低于DSS组(P=0.032)。此外,和DSS组相比,丹参酮IIA干预组小鼠结肠组织中性粒细胞浸润和活化程度明显减少,并伴有炎症因子水平显著下降(P<0.05)。结论在本实验条件下,丹参酮IIA对小鼠实验性结肠炎有明显的治疗作用,其机制可能与抑制中性粒细胞浸润、活化和减少炎症因子生成有关。Objective To investigate whether Tanshinone IIA has a protective role in treating experimental colitis through modulation of neutrophils. Methods Colitis was induced by giving 3% dextran sulfate sodium（ DSS） orally for 7 days in C57BL/6 mice.Meanwhile,mice were treated daily with Tanshinone IIA intraperitoneally. The severity of colitis was evaluated by calculating disease activity index（ DAI） and histological observation. Neutrophil infiltration and activation in the colons of mice were measured. Results The data showed that Tanshinone IIA significantly ameliorated the severity of DSS-induced colitis in mice,evidenced by the reduced DAI and improved colonic inflammation. In addition,Tanshinone IIA decreased neutrophil infiltration of intestinal mucosa and activation,as well as reduced colonic inflammatory cytokines in DSS-treated mice. Conclusion These results provided evidence that Tanshinone IIA had a therapeutic potential for alleviating inflammatory colitis in mice under this experimental system,which was possibly mediated by the immunomodulation of neutrophils.

关 键 词：丹参酮IIA 中性粒细胞 结肠炎 DSS 

分 类 号：R541[医药卫生—心血管疾病]