大黄素对实验性自身免疫性甲状腺炎小鼠辅助型T细胞亚群的影响  

Effects of emodin on T helper cell subsets of experimental autoimmune thyroiditis mice

作　　者：吴可人[1] 叶志鹏[1] 金法[1] 方蓉[1] 徐涛[1] 李宁[1] WU Keren YE Zhipeng JIN Fa FANG Rong XU Tao LINing(Department of Hepatobiliary Surgery, First Affiliated Hospital of Zhefiang Chinese Medical University, Hangzhou 310006, Zhejiang , China)

机构地区：[1]浙江中医药大学附属第一医院肝胆外科

出　　处：《中国临床药理学与治疗学》2017年第6期633-639,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：浙江省中医药科技计划资助(2014ZA037)

摘　　要：目的:研究大黄素对实验性自身免疫性甲状腺炎(experimental autoimmune thyroiditis,EAT)小鼠甲状腺的保护作用和机制。方法:通过过量碘剂诱导非肥胖型糖尿病(non-obese diabetic,NOD)小鼠建立EAT动物模型,造模4周后各实验组摄入不同剂量的大黄素。造模8周后检测小鼠血浆甲状腺球蛋白(Tg Ab)及甲状腺炎症程度以观察大黄素对EAT小鼠的保护作用。流式细胞术检测小鼠外周血、脾脏T细胞亚群,分析大黄素对EAT小鼠外周血、脾脏Th1、Th2细胞流式检测频率的影响。ELISA法检测血浆IL-4、IFN-γ水平。结果:(1)甲状腺病理学观察,各大黄素实验组较模型组甲状腺淋巴细胞浸润程度减轻,分级比较差异有统计学意义(P<0.01);(2)造模后的各组小鼠血浆Tg Ab水平明显升高,各实验组升高幅度低于模型组,组间有统计学差异(P<0.01);(3)造模后的各组小鼠血浆IL-4、IFN-γ、外周血单核细胞以及脾脏淋巴细胞中CD_3^+CD_4^+IL-4^+、CD_3^+CD_4^+IFN-γ^+、CD_3^+CD_8^+IL-4^+和CD_3^+CD+8IFN-γ^+T细胞频率均较对照组明显增高(P<0.01),但各实验组升高幅度低于模型组小鼠。结论:过量碘剂诱导NOD小鼠自身免疫性甲状腺炎造模是可行的;大黄素对造模小鼠甲状腺炎自身免疫反应有一定抑制作用。大黄素通过抑制CD_4^+CD_8~T淋巴细胞分泌IL-4和IFN-γ,从而抑制造模小鼠的自身免疫反应。AIM： To investigate the protective effect of emodin on thyroid in experimental autoimmune thyroiditis（ EAT） mice,and its mechanism.METHODS： EAT animal model was induced by iodine on non-obese diabetic（ NOD） mice. Four weeks after modeling, experimental groups were treated with emodin with different doses. The Tg Ab level in plasma and thyroid inflammation were detected eight weeks after modeling to evaluate the protective effect of emodin on EAT mice. T cell subset in peripheral blood and spleen were detected by flow cytometry. IL-4 and IFN-γ were measured by ELISA method. RESULTS：（1） The histopathological study revealed that inflammatory infiltration in thyroid was significant reduced compared with control group（ P 0. 01）.（ 2） Levels of plasma Tg Ab were significant increased in each group after modeling,and the increasing amplitudes in emodin treated groups were significantly less than that in model group（ P 0. 01）.（3） After modeling,levels of plasma IL-4,IFN-γ and the cell frequencies of CD_3~＋CD_4~＋IL-4~＋,CD_3~＋CD_4~＋IFN-γ~＋,CD_3~＋CD_8~＋IL-4~＋and CD_3~＋CD_8~＋IFN-γ~＋T cells in peripheral blood monocyte and splenic lymphocyte were significant increased in each group compared with the control group（ P 0. 01）. While the increasing amplitudes in emodin treated groups were less than that in model group. CONCLUSION： The EAT model is viable through an excessive iodine-induced method in NOD mice,and emodin shows a certain inhibitory effect on autoimmune response in EAT mice. This inhibitory effect could be performed by inhibiting the secretion of IFN-γand IL-4 in CD_4~＋and CD_8~＋T cells,and thereby inhibiting the autoimmune response in EAT mice.

关 键 词：实验性自身免疫性甲状腺炎 大黄素 TH细胞 NOD小鼠 

分 类 号：R965.2[医药卫生—药理学]