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消瘿合剂对自身免疫性甲状腺炎大鼠调节性T细胞/Th17细胞轴的影响

Effect of Xiaoying Decoction on Changes of Regulatory T Cells and Th17 Cells in Experimental Autoimmune Thyroiditis Rats

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【作者】 关溪赵亮刘力徐德生

【Author】 GUAN Xi;ZHAO Liang;LIU Li;XU Desheng;Department of Pharmacy,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine;Department of TCM Surgery,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine;

【机构】 上海中医药大学附属曙光医院药剂科上海中医药大学附属曙光医院中医外科

【摘要】 目的从纠正调节性T细胞(Treg)/Th17细胞轴紊乱角度,探讨消瘿合剂对自身免疫性甲状腺炎的作用机制。方法 SD大鼠分为正常对照组,模型对照组,雷公藤多苷组,消瘿合剂小、大剂量组。除正常对照组外,其他组建立实验性自身免疫甲状腺炎(EAT)模型。消瘿合剂小、大剂量组每日分别给予消瘿合剂浓缩液17.24,68.95 g·kg-1,雷公藤多苷组每日给予雷公藤混悬液6.25 mg·kg-1。连续灌胃8周。放射免疫法(RIA)检查血清游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、甲状腺球蛋白抗体(Tg Ab);光镜下观察甲状腺细胞形态;Real-time聚合酶链反应(RT-PCR)法检测大鼠脾脏Foxp3、白细胞介素(IL)-17mRNA表达;流式细胞术检测外周血Treg、Th17细胞比例。结果与正常对照组比较,模型对照组FT3、FT4、Tg Ab均升高(P<0.01,P<0.01,P<0.05)。与模型对照组比较,雷公藤多苷组、消瘿合剂大剂量组FT3、FT4、Tg Ab显著降低(均P<0.01)。正常对照组甲状腺炎症浸润评分0分,模型对照组4分,雷公藤多苷组4分,消瘿合剂小剂量组3.5分,消瘿合剂大剂量组2分。与模型对照组比较,消瘿合剂大剂量组炎症浸润评分差异有统计学意义(P<0.01)。与正常对照组比较,模型对照组Foxp3 mRNA表达降低,IL-17 mRNA表达升高(P<0.01)。与模型对照组比较,干预各组Foxp3mRNA均表达升高,IL-17mRNA表达降低。与正常对照组比较,模型对照组Treg细胞比例下降,Th17细胞比例升高(P<0.01)。与模型对照组比较,雷公藤多苷组、消瘿合剂大剂量组Treg细胞比例均升高,Th17细胞比例降低(P<0.01)。结论消瘿合剂对自身免疫性甲状腺炎模型的干预作用可能与上调Foxp3 mRNA表达,增加Treg细胞比例,减少IL-17mRNA表达,下调Th17细胞比例,即以纠正Treg/Th17细胞轴失衡有关。

【Abstract】 Objective To explore the mechanism of Xiaoying decoction on experimental autoimmune thyroiditis( EAT)rats in view of regulatory T cells and Th17 cells. Methods SD rats were divided into five groups,normal control group,model control group,tripterygium glycoside group,Xiaoying decoction low and high dose groups. Except for normal control group,the other groups were established the model of EAT. Rats in the Xiaoying decoction low,and high dose groups were given Xiaoying decoction of 17. 24 and 68. 95 g·kg-1; rats in the tripterygium glycoside group were given tripterygium glycoside 6. 25 mg·kg-1.The serum free triiodothyronine( FT3),free thyrocyte( FT4) and thyroglobulin antibody were detected by RIA method. Thyrocyte morphology was observed under optical microscope. The expression levels of Foxp3 mRNA and IL-17 mRNA were detected by real-time PCR. The changes of Treg cells and Th17 cells were analyzed by flow cytometry. Results Compared with the normal control group,FT3,FT4 and Tg Ab were increased in the model control group( P < 0. 01,P < 0. 01,P < 0. 05). Compared with the model control group,FT3,FT4 and Tg Ab were decreased in tripterygium glycoside group and Xiaoying decoction high dose group( P < 0. 05). The infiltration score in the normal control group,model control group,tripterygium glycoside group,Xiaoying decoction low and high dose groups were 0,4,4,3. 5,2. Compared with model control group,the infiltration was improved( P <0. 01). Foxp3 mRNA expression was decreased while IL-17 mRNA increased in the model control group as compared with the normal control group( P < 0. 01). In contrast,the expression of Foxp3 mRNA was increased and IL-17 mRNA expression was decreased in Xiaoying decoction low and high dose groups,tripterygium glycoside group as compared with the model control group( P < 0. 05). Compared with the normal control group,rats in the model control group had fewer Treg cells and more Th17 cells( P < 0. 01). Compared with the model control group,the percentage of Treg cells was elevated and Th17 cells was reduced in tripterygium glycoside group and Xiaoying decoction high dose groups( P < 0. 01). Conclusion The therapeutic mechanism of Xiaoying decoction on EAT rats may be related to changing the percentage of regulatory T cells and Th17 cells with up-regulating the expression of Foxp3 mRNA and down-regulating the expression of IL17 mRNA.

【基金】 上海市进一步加快中医药事业发展三年行动计划(2014年-2016年)中医药专门人才计划(ZY3-RCPY-3-1040);国家(中医专业)临床药学重点专科培育项目(ZP0901YX010)
  • 【文献出处】 医药导报 ,Herald of Medicine , 编辑部邮箱 ,2017年02期
  • 【分类号】R285.5
  • 【被引频次】19
  • 【下载频次】222
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