Research on the regulation and mechanism of Buzhong Yiqi Decoction for immune imbalance in experimental autoimmune thyroiditis rats

QIAO Jia-jun; YUAN Quan; ZHAO Yi-kun; XIA Zhong-yuan

doi:10.16025/j.1674-1307.2023.03.010

您当前的位置：

首页 >

文章列表页 >

Research on the regulation and mechanism of Buzhong Yiqi Decoction for immune imbalance in experimental autoimmune thyroiditis rats

更新时间：2023-06-16

- Research on the regulation and mechanism of Buzhong Yiqi Decoction for immune imbalance in experimental autoimmune thyroiditis rats
- Beijing Journal of Traditional Chinese Medicine Vol. 42, Issue 3, Pages: 268-274(2023)
- 作者机构：
  
  1.中日友好医院中医外科，北京100029
  2.北京中医药大学，北京100029
- 作者简介：
- 基金信息：
- DOI：10.16025/j.1674-1307.2023.03.010
  CLC：
扫描看全文
乔佳君，袁泉，赵翊昆，等.补中益气汤对实验性自身免疫性甲状腺炎大鼠免疫失衡的调节及作用机制研究［J］.北京中医药，2023，42（3）：268-274.

QIAO Jia-jun,YUAN Quan,ZHAO Yi-kun,et al.Research on the regulation and mechanism of Buzhong Yiqi Decoction for immune imbalance in experimental autoimmune thyroiditis rats[J]. Beijing Journal of Traditional Chinese Medicine,2023,42(03):268-274.
乔佳君，袁泉，赵翊昆，等.补中益气汤对实验性自身免疫性甲状腺炎大鼠免疫失衡的调节及作用机制研究［J］.北京中医药，2023，42（3）：268-274. DOI： 10.16025/j.1674-1307.2023.03.010.

QIAO Jia-jun,YUAN Quan,ZHAO Yi-kun,et al.Research on the regulation and mechanism of Buzhong Yiqi Decoction for immune imbalance in experimental autoimmune thyroiditis rats[J]. Beijing Journal of Traditional Chinese Medicine,2023,42(03):268-274. DOI： 10.16025/j.1674-1307.2023.03.010.

摘要

目的,2,基于TGF-β/Smad信号通路探讨补中益气汤调节实验性自身免疫性甲状腺炎（experimental autoimmune thyroiditis，EAT）大鼠模型免疫失衡的作用。,方法,2,雌性SD大鼠40只，随机选取10只为空白组，其余大鼠使用高碘饮水联合弗氏佐剂与猪甲状腺球蛋白（pTG）免疫注射建立EAT大鼠模型，成模后随机分为模型组、硒酵母组、补中益气组3组，每组10只，连续灌胃2个月。检测大鼠血清抗甲状腺抗体，观察甲状腺组织病理切片，并通过流式细胞术检测脾脏Th17、Treg比例，RT-PCR和Western blot检测TGF-β/Smad信号通路的相关基因和蛋白表达。,结果,2,与空白组比较，模型组甲状腺过氧化物酶抗体（TPOAb）、甲状腺球蛋白抗体（TGAb）水平升高（,P,<,0.05），光镜下模型组甲状腺组织部分滤泡破坏，可见大量淋巴细胞浸润，说明造模成功。且与空白组比较，模型组Smad2、Smad3、Foxp3 mRNA低表达（,P,<,0.05），Foxp3蛋白低表达（,P,<,0.05），同时Th17%升高（,P,<,0.05）。干预后，与模型组比较，硒酵母组与补中益气组TPOAb与TGAb水平下降（,P,<,0.05），且2组甲状腺组织病理损伤均有不同程度改善。与模型组比较，补中益气组TGF-β,1,、Smad2、Smad3 mRNA高表达，且Smad4蛋白、Foxp3蛋白高表达，Treg%升高（,P,<,0.05）。与硒酵母组比较，补中益气组TGF-β,1,、Smad2、Smad3、Foxp3 mRNA和Smad4蛋白亦呈现高表达状态，Treg%升高（,P,<,0.05）。与模型组比较，硒酵母组和补中益气组Th17%差异无统计学意义（,P,>,0.05）。,结论,2,补中益气汤能够显著改善EAT大鼠的自身免疫性甲状腺炎，其作用机制可能与调节TGF-β/Smad通路，增加Foxp3表达，进而调节Th17/Treg失衡有关。

Abstract

Objective,2,To discuss the effect of Buzhong Yiqi Decoction on regulating the immune imbalance of experimental autoimmune thyroiditis（EAT） rat model based on TGF-β/Smad signal pathway.,Methods,2,Among Forty female SD rats，10 were randomly selected as the blank group，the rest were immunized with high iodine drinking water combined with Freund's adjuvant and porcine thyroglobulin（pTG） to establish EAT rat model. After the model was established，they were randomly divided into three groups（10 rats in each group），including model group，selenium yeast group，Buzhong Yiqi group，and were gavaged continuously for two months. Anti-thyroid antibody in rat serum were detected，the pathological section of thyroid tissue observed，Th17 and Treg ratio of spleen were detected by flow cytometry，the expression of genes and proteins related to TGF- β/ Smad signaling pathway were detected by RT-PCR and Western blot.,Results,2,Compared with the blank group， the levels of TPOAb and TGAb in the model group were increased（,P,<,0.05）. Under the light microscope， part of the thyroid follicles in the model group were destroyed，and a large number of lymphocytes infiltration were seen， indicating that the model was successful. Compared with the blank group，the mRNA expression of Smad2，Smad3 and Foxp3 in the model group was low（,P,<,0.05），the protein expression of Foxp3 was low（,P,<,0.05），and the Th17% increased（,P,<,0.05）. After the intervention，compared with the model group，the levels of TPOAb and TGAb in the selenium yeast group and Buzhong Yiqi group decreased（,P,<,0.05），and the pathological damage of thyroid tissue in the two groups were improved variously. Compared with the model group，TGF-β 1，Smad2 and Smad3 mRNA in the Buzhong Yiqi group were highly expressed，Smad4 protein and Foxp3 protein were highly expressed，and Treg% increased（,P,<,0.05）. Compared with selenium yeast group，the TGF-β 1，Smad2， Smad3， Foxp3 mRNA and Smad4 protein in Buzhong Yiqi group also showed high expression，and Treg% increased（,P,<,0.05）. However，compared with the model group，there was no significant difference in Th17% between the selenium yeast group and the Buzhong Yiqi group（,P,>,0.05）.,Conclusion,2,Buzhong Yiqi Decoction can significantly improve autoimmune thyroiditis in EAT rats，and its mechanism may be related to theregulation of TGF- β/ Smad pathway，increase of the expression of Foxp3， and then regulation of imbalance of Th17/Treg.

关键词

补中益气汤自身免疫性甲状腺炎桥本氏甲状腺炎作用机制免疫调节TGF-β/Smad信号通路大鼠

Keywords

Buzhong Yiqi Decoctionexperimental autoimmune thyroiditisHashimoto's thyroiditismechanism of actionimmunomodulationTGF-β/Smad signal pathwayrats

references

LI Y, TENG D, BA J, et al. Efficacy and safety of long-term universal salt iodization on thyroid disorders: epidemiological evidence from 31 provinces of mainland China [J]. Thyroid, 2020, 30(4): 568-579.

李颖, 兰永连, 梁毓, 等. 自身抗体与不孕症的相关性研究进展 [J]. 中国优生与遗传杂志, 2019, 27(4): 385-386，390.

韩静, 刘守尧. 桥本氏甲状腺炎中西医治疗研究进展 [J]. 中华中医药杂志, 2019, 34(11): 5327-5330.

韩静. 扶正消瘿方治疗桥本氏甲状腺炎（HT）的临床研究 [D].北京：北京中医药大学, 2019.

周玉, 关青青, 韩静, 等. 补中益气汤加减治疗亚临床甲状腺功能减退症临床研究 [J]. 安徽中医药大学学报, 2017, 36(6): 30-34.

韩静, 袁泉, 刘昕怡, 等. 补中益气颗粒对EAT大鼠甲状腺功能、甲状腺抗体的影响 [J]. 北京中医药大学学报, 2018, 41(12): 1007-1011.

刘守尧, 关青青, 韩静, 等. 补中益气颗粒对EAT大鼠Treg/Th17细胞因子表达的影响 [J]. 北京中医药大学学报, 2019, 42(5): 404-408，415.

GAFFEN SL, JAIN R, GARG AV, et al. The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing [J]. Nat Rev Immunol, 2014, 14(9): 585-600.

ZENOBIA C, HAJISHENGALLIS G. Basic biology and role of interleukin-17 in immunity and inflammation [J]. Periodontol 2000, 2015, 69(1): 142-159.

VERNAL R, GARCIA-SANZ JA. Th17 and Treg cells, two new lymphocyte subpopulations with a key role in the immune response against infection [J]. Infect Disord Drug Targets, 2008, 8(4): 207-220.

LIU Y, TANG X, TIAN J, et al. Th17/Treg cells imbalance and GITRL profile in patients with Hashimoto's thyroiditis [J]. Int J Mol Sci, 2014, 15(12): 21674-21686.

LI C, YUAN J, ZHU Y F, et al. Imbalance of Th17/Treg in different subtypes of autoimmune thyroid diseases [J]. Cell Physiol Biochem, 2016, 40(1-2): 245-252.

SAFDARI V, ALIJANI E, NEMATI M, et al. Imbalances in T cell-related transcription factors among patients with hashimoto's thyroiditis [J]. Sultan Qaboos Univ Med J, 2017, 17(2): 174-180.

GUO Y, ZYNAT J, XING S, et al. Immunological changes of T helper cells in flow cytometer-sorted CD4+ T cells from patients with Hashimoto's thyroiditis [J]. Exp Ther Med, 2018, 15(4): 3596-3602.

孙庆凯, 陈占玲, 李春华, 等. 白细胞介素6/转化生长因子-β信号异常在桥本甲状腺炎辅助性T细胞17/调节性T细胞失衡中的作用研究 [J]. 中华内分泌代谢杂志, 2015, 31(4): 320-326.

ZHOU L, LOPES JE, CHONG MM, et al. TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function [J]. Nature, 2008, 453(7192): 236-240.

MORITA Y, ISMAIL DM, ELKON KB, et al. Dichotomous response to transforming growth factor β after T cell receptor activation by naive CD4+ T cells from DBA/1 mice: enhanced retinoic acid receptor-related orphan nuclear receptor γt expression yet reduced FoxP3 expression [J]. Arthritis Rheum, 2011, 63(1): 118-126.

MENG XM, TANG PM, LI J, et al. TGF-β/Smad signaling in renal fibrosis [J]. Frontiers in physiology, 2015, 6:82.

TRONCONE E, MARAFINI I, STOLFI C, et al. Transforming growth factor-β1/Smad7 in intestinal immunity, inflammation, and cancer [J]. Front Immunol, 2018, 9:1407.

PEREIRA LMS, GOMES STM, ISHAK R, et al. Regulatory T cell and forkhead box protein 3 as modulators of immune homeostasis [J]. Front Immunol, 2017, 8:605.

周怡锦, 田新磊, 祝志朋, 等. 黄芪甲苷通过抑制IL-6/JAK2/STAT3信号通路调节肺脾气虚反复呼吸道感染模型大鼠的Th17/Treg细胞平衡 [J]. 中药材, 2022, 10: 2473-2478.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Study on mechanism of protective effect in nonalcoholic fatty liver rats by TiaoganQuzhi Formula based on miR-34a/SIRT1/PPARα signaling pathway

Mechanism of Rhizoma coptidis in improving diarrhea in ulcerative colitis through regulating the expression of AQPs protein in colonic mucosal epithelial cells

Effect and mechanism of Bushen Zhuyun Decoction in treatment of model rats with luteal phase defect

Effect of Jianpi Liqi Decoction on the improvement of micro-inflammation in the duodenum of rats with functional dyspepsia

Efficacy of Naoan Dropping Pill on the intervention of migraine under fatigue state and the mechanism of oxidative stress based on Nrf2/ARE pathway

Related Author

No data

Related Institution

Beijing Institute of Traditional Chinese Medicine

Digestive Center of Beijing Traditional Chinese Medicine Hospital Affiliated to the Capital Medical University

Beijing University of Traditional Chinese Medicine

Department of Gastroenterology，the Second Affiliated Hospital of Guangzhou University of Chinese Medicine

The First Clinical Medical College of Henan University of Chinese Medicine

⁰