牛蒡子苷元对免疫性血小板减少模型的药效及机理

Effects and mechanism of arctigenin in different animal models of ITP

目的考察牛蒡子苷元对免疫性血小板减少疾病(immune thrombocytopenic purpura,ITP)动物模型的药效学,并初步研究其作用机制。方法采用SD大鼠腹腔注射兔抗大鼠血小板(platelet,PLT)抗体血清制备被动型ITP动物模型,Balb/c小鼠腹腔注射大鼠血小板抗原制备小鼠交叉免疫反应型ITP模型,SD大鼠皮下注射环磷酰胺制备大鼠药物诱导型血小板减少模型,通过血细胞计数仪检测以上3种动物模型全血PLT数量,并研究牛蒡子苷元对ITP模型的药效作用;正常Balb/c小鼠给予牛蒡子苷元1.0 mg·kg-1·d-1后,利用流式技术检测脾脏淋巴细胞Treg细胞比率,研究牛蒡子苷元药理作用机制。结果成功构建3种ITP模型,牛蒡子苷元能显著性提高被动型ITP模型与交叉免疫反应型ITP模型的PLT数量,与模型组相比有显著性差异(P<0.05);对环磷酰胺造成的模型作用不明显(P>0.05);牛蒡子苷元能显著性提高正常小鼠脾脏淋巴细胞Treg细胞比率(P<0.05)。结论牛蒡子苷元对免疫性血小板减少动物模型取得较好的治疗效果,这可能与其升高Treg细胞比率有关。

Objective To investigate the effects and mechanism of arctigenin on thrombocytopenia （ITP）by constructing three different immune ITP animal models. Methods Passive ITP animal model was constructed by using intraperitoneal injection of sera containing rabbit anti rat platelet（PLT） antibody;rat platelets, as an- tigen, were injected to mice by peritoneal injection to cause the thrombocytopenia because of cross immune reaction; cyclophosphamide, injected by hypodermic with 150 mg. kg - 1·d - 1, was used to construct drug in- duced thrombocytopenia model in rats. The concentration of PLTs in whole blood of every mouse in each group of the three models, for researching the pharmacodynamics of arctigenin effecting on ITP models, were detected by blood cell counting instrument. Normal BALB/c mice were given arctigenin of 1 mg. kg- 1· d- 1, and the concentration of Treg cells in the spleen lymphocyte suspension were detected by flow cytometry, in order to research the pharmacological mechanism of arctigenin. Results Each of the three ITP models was constructed successfully. Arctigenin significantly increased the PLT number of both passive ITP model and ITP model because of cross immune reaction, （ P 〈 0.05, compared with the model group）. But, the effect of arctigenin on thrombocytopenia, induced by cyclophosphamide, was not obvious （ P 〉 0.05, compared with the model group）. Arctigenin could significantly improve the ratio of Treg cells in the spleen lymphocyte suspension of the normal mice （ P 〈 0.05, compared with the model group）. Conclusions Arctigenin has a better therapeutic effect on immune thrombocytopenic animal models, which may be related to the ability of arctigenin for increasing the ratio of Treg cells.