Sophocarpine对三硝基苯磺酸诱导的小鼠结肠炎的作用及其机制

Effect of Sophocarpine on TNBS-induced colitis in mice

目的明确槐果碱(Sophocarpine)对三硝基苯磺酸(TNBS)诱导的小鼠结肠炎的作用与可能机制。方法采用6~8周龄雄性Balb/c小鼠,建立TNBS结肠炎模型后随机分为模型组及干预组。干预组接受Sophocarpine腹腔注射(每天50 mg/kg),模型组接受等量生理盐水。干预4 w后处死小鼠,采用免疫学、组织学等技术手段分析小鼠肠道炎症、肠黏膜免疫及肠屏障功能改变。结果干预组结肠组织炎症评分、结肠黏膜炎症介质干扰素(IFN)-γ及肿瘤坏死因子(TNF)-α水平显著低于模型组,而白细胞介素(IL)-10水平、脾及肠系膜淋巴结Treg细胞比例、肠黏膜紧密连接蛋白ZO-1及claudin-1水平均显著高于模型组(P<0.01);肠屏障通透性实验显示,干预组血清异硫氰酸荧光素(FITC)-葡聚糖浓度显著低于模型组(P<0.01)。干预组肠黏膜核苷酸结合寡聚化结构域样受体蛋白(NLRP)3、凋亡相关斑点样蛋白(ASC)及Caspase-1水平均显著低于模型组(P<0.01)。结论Sophocarpine可改善结肠炎小鼠肠道炎症,可能与保护肠黏膜屏障和抑制NLRP3炎症小体有关。

Objective To determine the effect and possible mechanism of Sophocarpine on trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice.Methods Male Balb/c mice aged 6~8 weeks were used to establish TNBS colitis model and randomly divided into model and intervention groups. The intervention group received daily intraperitoneal injection of Sophocarpine (50 mg/kg) and the model group received the same amount of normal saline. After 4 weeks of intervention, the mice were sacrificed and immunological, histological and other techniques were used to analyze intestinal inflammation, intestinal mucosal immunity and intestinal barrier function.Results The colonic tissue inflammation score of the intervention group was significantly lower than that of the model group ( P <0.01). The levels of IFN-γ and TNF-α in colonic mucosal inflammatory mediators in the intervention group were significantly lower than those in the model group ( P <0.01), while IL-10 levels were significantly higher than those in the model group ( P <0.01). The proportion of Treg cells in the spleen and mesenteric lymph nodes of the intervention group were significantly higher than those of the model group ( P <0.01). The levels of tight junction proteins ZO-1 and claudin-1 in the intestinal mucosa of the intervention group were significantly higher than those in the model group ( P <0.01). The intestinal barrier permeability test showed that the serum FITC-glucan concentration in the intervention group was significantly lower than that of the model group ( P <0.01). The levels of NLRP3, ASC and Caspase-1 in the intestinal mucosa of the intervention group were significantly lower than those in the model group ( P <0.01).Conclusions Sophocarpine improves intestinal inflammation in colitis mice and might be associated with protection of the intestinal mucosal barrier and inhibition of NLRP3 inflammatory bodies.