苦参素对实验性自身免疫性甲状腺炎大鼠Th1/Th2细胞平衡及相关通路的影响

doi:10.12300/j.issn.1674-5817.2020.086

摘要/Abstract

摘要： 目的探讨苦参素对实验性自身免疫性甲状腺炎（EAT）大鼠炎性反应、辅助性T淋巴细胞（Th）1/Th2、单核细胞趋化蛋白-1（MCP-1）及细胞表面趋化因子受体2(CCR2)信号的影响。方法将75只Lewis大鼠按随机数字表法分为对照组、模型组和苦参素低、中、高剂量组。用免疫猪甲状腺球蛋白(pTG)诱导建立EAT大鼠模型,苦参素低、中、高剂量组分别灌胃0.2、0.4和0.6 g/kg的苦参素,给药体积2 mL,对照组和模型组均给予等体积生理盐水,隔日1次,共4周。HE染色观察大鼠甲状腺组织形态学变化;ELISA法检测血清中促甲状腺激素(TSH)、抗甲状腺球蛋白抗体（TGAb）和甲状腺过氧化物酶抗体（TPOAb）,以及细胞因子干扰素-γ（IFN-γ）、白细胞介素（IL）-12、IL-4和IL-10水平;蛋白质印迹法检测甲状腺组织中MCP-1/CCR2信号轴。结果与对照组相比,模型组TSH、TGAb、TPOAb、IFN-γ、IL-12、IFN-γ/IL-4、IL-12/IL-10、NF-κBp65及MCP-1、CCR2蛋白水平均明显升高,IL-4、IL-10水平明显降低（均P<0.05）;苦参素低、中、高剂量组大鼠TSH、TGAb、TPOAb、IFN-γ、IL-12、IFN-γ/IL-4、IL-12/IL-10、NF-κBp65及MCP-1、CCR2蛋白水平均明显降低,IL-4、IL-10水平明显升高（均P<0.05）,且呈剂量依赖性。结论苦参素能抑制甲状腺抗体生成,下调Th1型细胞因子,上调Th2型细胞因子,进而降低Th1和Th2比值,并抑制MCP-1/CCR2信号轴,发挥对自身免疫性甲状腺炎大鼠的保护作用。

关键词: 苦参素, 实验性自身免疫性甲状腺炎, Th1/Th2, MCP-1/CCR2信号, Lewis大鼠

Abstract: Objective To investigate the effects of matrine on inflammation, helper T lymphocytes (Th)1/Th2, and monocyte chemoattractant protein-1 (MCP-1)/cell surface chemokine receptor 2(CCR2) signaling in rats with experimental autoimmune thyroiditis (EAT). Methods Seventy-five Lewis rats were divided into control, model, and low-, medium-, and high-dose matrine groups using the random number table method (n = 15 each). The EAT rat model was induced by immunization with porcine thyroglobulin (pTG). The low-, medium-, and high-dose groups were intragastrically administered 0.2, 0.4, and 0.6 g/kg matrine, respectively, at a volume of 2 mL. Rats in the control and model groups were given 2 mL of normal saline, once every other day for 4 weeks. The histomorphological changes in the thyroid were observed by hematoxylin and eosin (HE) staining. Serum levels of thyroid stimulating hormone (TSH), anti-thyroglobulin antibody (TGAb), thyroid peroxidase antibody (TPOAb), cytokine interferon-γ (IFN-γ), and interleukin (IL)-12, IL-4, and IL-10 were detected by ELISA. Results Compared with the TSH, TGAb, TPOAb, IFN-γ, IL-12, IFN-γ/IL-4, IL-12/IL-10, nuclear factor-kappa B p65 (NF-κBp65), MCP-1, and CCR2 protein levels in the control group, those in the model group were significantly increased, and the levels of IL-4 and IL-10 were significantly decreased (P < 0.05). After matrine treatment, TSH, TGAb, TPOAb, IFN-γ, IL-12, IFN-γ/IL-4, IL-12/IL-10, NF-κBp65, MCP-1, and CCR2 protein levels were significantly decreased, and IL-4 and IL-10 levels were significantly increased (P < 0.05); the differences were statistically significant (P < 0.05). Conclusion Matrine can inhibit the production of thyroid antibodies, downregulate Th1 cytokines, and upregulate Th2 cytokines, thus reducing the Th1/Th2 ratio and inhibiting the MCP-1/CCR2 signaling axis, thus playing a protective role in EAT.

Key words: Matrine, Experimental autoimmune thyroiditis, Th1/Th2 cells, MCP-1/CCR2 signaling, Lewis rats

中图分类号:

Q95-33
R-332

姚婷,高原,曾芳馨. 苦参素对实验性自身免疫性甲状腺炎大鼠Th1/Th2细胞平衡及相关通路的影响[J]. 实验动物与比较医学, 2021, 41(3): 244-251. DOI: 10.12300/j.issn.1674-5817.2020.086.

YAO Ting,GAO Yuan,ZENG Fangxin. Effects of Matrine on Th1/Th2 Balance and Related Pathways in Rats with Experimental Autoimmune Thyroiditis[J]. Laboratory Animal and Comparative Medicine, 2021, 41(3): 244-251. DOI: 10.12300/j.issn.1674-5817.2020.086.

图/表 5

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