α-硫辛酸干预对自身免疫性甲状腺炎发病的影响Effects of alpha-lipoic acid on the immunological mechanism of autoimmune thyroiditis
杨榕,范晨玲
YANG Rong,FAN Chen-ling
摘要(Abstract):
目的观察不同剂量硫辛酸干预对高碘诱发的自身免疫性甲状腺炎(autoimmune thyroiditis,AIT)的动物模型中CD4~+CD25~+调节性T细胞和Th17细胞的变化及影响,探讨硫辛酸治疗AIT的免疫学机制。方法选取饮用质量浓度50 mg·L-1碘化钠水的NOD.H-2h4雌鼠,注射不同剂量硫辛酸干预。采用HE染色法观察淋巴细胞浸润的情况并进行甲状腺炎症程度的评分;测定血清甲状腺球蛋白抗体(Tg Ab)的水平;再用免疫荧光染色流式细胞仪分析CD4~+CD25~+Foxp3~+调节性T细胞和Th17细胞比例变化;实时定量RT-PCR法检测Foxp3 mRNA、IL-17mRNA和RORγtmRNA的表达水平。结果与AIT非干预组相比,硫辛酸干预组NOD.H-2h4小鼠CD4~+CD25~+Foxp3~+调节性T细胞比例及Foxp3 mRNA表达量均明显升高(P<0.05);脾细胞中Th17细胞比例及其转录因子IL-17mRNA和RORγtmRNA表达水平均明显减低(P<0.01)。但不同剂量硫辛酸干预组之间比较无显著性差异(P>0.05)。同时,硫辛酸干预组NOD.H-2h4小鼠血清Tg Ab滴度以及甲状腺内淋巴细胞浸润的程度均较同周龄非干预组小鼠明显降低(P<0.05)。结论α-硫辛酸对AIT有治疗效果。
Objective The aim of the present study was to investigate the effects of treatment with different dose of alpha-lipoic acid on the number of CD4~+CD25~+regulatory T cells and Th17 cells in spleen of autoimmune thyroiditis( AIT) model NOD. H-2h4 mice,and to explore the potential therapeutic effect of alpha-lipoic acid on AIT. Methods NOD. H-2h4 mice were fed with 50 mg·L-1Na I water for 8 weeks to establish the animal models of AIT. At the same time,the mice were fed with 50 mg·L-1Na I water supplied with different dose Alpha-lipoic acid for 8 weeks. After 8 weeks,the thyroid tissues of mice were removed and weighted. The lymphocytic infiltration in thyroids was observed by HE-staining and the Tg Ab titers in serum wasmeasured by ELISA method. The ratio of CD4~+CD25~+Foxp3~+T cells and Th17 cells in splenic mononuclear cells was detected by multicolor flowcytometry,and the expression of Foxp3 mRNA,IL-17 mRNA,and RORγtmRNA in splenocytes was measured by real-time RT-PCR. Results Compared to AIT mice untreated with alpha-lipoic acid,the mice treated with alpha-lipoic acid for 8 weeks had higher numbers of CD4~+CD25~+Foxp3~+T cells in the splenic mononuclear cells and increased expressions of Foxp3 mRNA in splenocytes( P < 0. 05). The percentage of Th17 cells and expressions of IL-17 mRNA,RORγ tmRNA were reduced significantly in alpha-lipoic acid treated group( P < 0. 01),even thought this change was alphalipoic dose independent( P > 0. 05). Furthermore,with the treatment using alpha-lipoic acid,the serum Tg Ab titer of mice was also decreased significantly( P < 0. 01),and histological appearance of thyroids was improved. Conclusions Alpha-lipoic acid has therapeutic effect on AIT.
关键词(KeyWords):
自身免疫性甲状腺炎;α-硫辛酸;调节性T细胞;Th17细胞
autoimmune thyroiditis;alpha-lipoic acid;regulatory T cell;Th17 cell
基金项目(Foundation): 辽宁省自然科学基金资助项目(201602431)
作者(Author):
杨榕,范晨玲
YANG Rong,FAN Chen-ling
DOI: 10.14066/j.cnki.cn21-1349/r.2017.05.011
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