青蒿素纳米球口服减轻自发性溃疡性结肠炎小鼠炎症

Oral administration of artemisinin nanospheres alleviates inflammation in mice with spontaneous ulcerative colitis

目的 研究旨在探讨β乳球蛋白(BLG)纳米颗粒封装的青蒿素(ART)对Winnie自发性溃疡性结肠炎小鼠模型的抗炎疗效。方法 制备BLG-ART纳米颗粒,并评价其对ART的溶解度和稳定性的影响。采用葡聚糖硫酸钠盐(DSS)诱导小鼠结肠炎模型,比较ART直接灌胃和使用BLG-ART灌胃的给药方式对小鼠的治疗效果。将Winnie小鼠随机分为空白组、 ART组和BLG-ART组。ART组小鼠灌胃给予50 mg/kg ART, BLG-ART组小鼠灌胃给予等剂量的BLG-ART纳米颗粒PBS分散液,空白组小鼠灌胃给予等量PBS,持续16 d。测定各组小鼠体质量和疾病活动指数(DAI), HE染色观察小鼠肠道组织病理变化,实时定量PCR检测小鼠结肠组织肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、 IL-10和IL-17的mRNA表达水平。结果 与ART组和空白组相比,治疗16 d后BLG-ART组小鼠体质量增加,DAI降低;小鼠近端和远端结肠区域隐窝结构恢复、杯状细胞损失减少、中性粒细胞浸润降低,促炎和抗炎细胞因子的mRNA表达水平显著下调。结论 ART-BLG处理减轻自发性溃疡性结肠炎小鼠的肠道炎症反应。

Objective To investigate the anti-inflammatory effect of artemisinin(ART)encapsulated byβ-lactoglobulin(BLG)nanoparticles on Winnie spontaneous ulcerative colitis mouse model.Methods BLG-ART nanoparticles were prepared and their effects on the solubility and stability of ART were evaluated.A mouse model of colitis induced by dextran sulfate sodium(DSS)was used to compare the therapeutic effects of artemisinin(ART)administered by direct gavage and artemisinin encapsulated byβ-lactoglobulin nanoparticles(BLG-ART)administered by gavage.Winnie mice were randomly divided into blank group,ART group and BLG-ART group.Mice in the ART group were given 50 mg/kg ART by gavage;mice in the BLG-ART group were given the same dose of BLG-ART nanoparticle PBS dispersion by gavage;mice in the blank group were given the same amount of PBS by gavage,for 16 days.The body mass and disease activity index(DAl)of each group of mice were measured.HE staining was used to observe the pathological changes of mouse intestinal tissue,and real-time quantitative PCR was used to detect the mRNA expression levels of TNF-α,interleukin 1β(IL-1β),IL-10 and IL-17 in mouse colon tissue.Results Compared with the ART group and the blank group,the body mass of the BLG-ART group increased and the DAl decreased after 16-day treatment;the crypt structure of the proximal and distal colon regions of the mice recovered;goblet cell loss decreased;neutrophil infiltration decreased and the mRNA expression levels of pro-inflammatory and anti-inflammatory cytokines were significantly down-regulated.Conclusion ART-BLGcanalleviate intestinal inflammation in spontaneous ulcerative colitis mice.