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  

Effects of Matrine on Th1/Th2 Balance and Related Pathways in Rats with Experimental Autoimmune Thyroiditis

作　　者：姚婷 高原 曾芳馨[2] YAO Ting;GAO Yuan;ZENG Fangxin(Department of Endocrinology,Second Affiliated Hospital of Chengdu Medical College·China National Nuclear Corporation 416 Hospital,Chengdu 610051,China;Department of Endocrinology and Rheumatism&Immunology,Dazhou Integrated TCM&Western Medicine Hospital,Dazhou 635000,China)

机构地区：[1]成都医学院第二附属医院·核工业四一六医院内分泌科,成都610051 [2]达州市中西医结合医院内分泌风湿免疫科,达州635000

出　　处：《实验动物与比较医学》2021年第3期244-251,共8页Laboratory Animal and Comparative Medicine

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、TPCAb、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、TPCAb、IFN-γ、IL-12、IFN-γ/IL-4、IL-12/1L-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。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.

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 

分 类 号：Q95-33[生物学—动物学] R-332[医药卫生]