目的 探究化痰散结方对Graves病（GD）小鼠Th2细胞因子的影响。方法 采用重组腺病毒Ad-TSHR289于第1、4、7周3次免疫BALB/c雌性小鼠制备GD模型，第10周将GD模型小鼠随机分为模型组、甲巯咪唑组、化痰散结组，另设同周龄正常小鼠为对照，每组8只，灌胃给药6周。放射免疫法检测血清中TRAb、T4含量，HE染色观察甲状腺组织形态学变化，Luminex细胞因子液相悬浮芯片检测Th2细胞相关因子差异。结果 与正常组相比，模型组小鼠T4、TRAb明显升高（P < 0.001），HE染色显微镜下可见滤泡上皮细胞增生、滤泡腔内凸等形态学改变。化痰散结组、甲巯咪唑组T4、TRAb较模型组降低（P < 0.05），化痰散结组甲状腺组织形态较模型组改变明显，甲巯咪唑组甲状腺组织形态较模型组有改变，但不显著。模型组IL-6、IL-10、IL-13水平较正常组显著升高（P < 0.05）；化痰散结组与甲巯咪唑组IL-6、IL-10、IL-13水平较模型组呈现不同程度降低，其中化痰散结组中IL-6以及甲巯咪唑组中IL-6降低显著（P < 0.05）。结论 化痰散结法能够改善GD小鼠甲状腺功能与组织形态，并能降低Th2细胞因子IL-6、IL-10、IL-13的表达。
Objective To explore the effect of reducing phlegm and resolving masses on cytokines expression of Th2 cell in Graves"s disease (GD) mice. Methods GD model was established by immunizing BALB/c female mice with recombinant adenovirus Ad-TSHR289 3 times at 1st, 4th, 7th week. At 10th week, GD model mice were randomly divided into a model group, a methimazole group and a reducing phlegm and resolving masses group. Other normal mice of the same age were set as control group, with 8 mice in each group. They were given intragastric administration for 6 weeks. The levels of TRAb and T4 in serum were detected by radioimmunoassay. The morphological changes of thyroid tissue were observed by HE staining and the differences of Th2 cell related factors were detected by Luminex liquid suspension chip. Results Compared with the normal group, T4 and TRAb in the model group increased significantly (P < 0.001) and the morphological changes of follicular epithelial cell proliferation and intrafollicular convexity were observed under HE staining microscope. The T4 and TRAb of the reducing phlegm and resolving massed and methimazole group were lower than those of the model group (P < 0.05). The morphology of thyroid tissue in reducing phlegm and resolving masses was significantly changed compared with that in the model group, while that in methimazole group was not changed significantly. The levels of IL-6, IL-10 and IL-13 in the model group were significantly higher than those in the normal group (P < 0.05). Compared with the model group, the levels of IL-6, IL-10 and IL-13 in the reducing phlegm and resolving masses and methimazole group were decreased. Moreover, the level of IL-6 in reducing phlegm and resolving masses group and IL-6 in methimazole group were significantly lower than those in the model group (P < 0.05). Conclusion The method of resolving phlegm and dispersing stagnation can improve the thyroid function and histomorphology of GD mice, meanwhile reducing the expression of Th2 cytokines IL-6, IL-10 and IL-13 which related with Th2 cell.
＊ ＊项目基金;国家自然科学基金委员会面上项目 81774293;国家自然科学基金委员会面上项目 81373593＊ ＊项目基金;国家自然科学基金委员会面上项目（81774293）：化痰散结法对Graves病小鼠免疫耐受开关机制及其修饰的影响，负责人：刘喜明；国家自然科学基金委员会面上项目（81373593）：化痰散结法对Graves病小鼠模型甲状腺肿大与激素合成下游事件的影响，负责人：刘喜明。