1,25(OH)_(2)D_(3)通过抑制TLR2/NF-κB信号通路保护实验性自身免疫性甲状腺炎大鼠甲状腺功能研究  

1,25(OH)_(2)D_(3) protects thyroid functions in experimental autoimmune thyroiditis rats by inhibiting the TLR2/NF-κB signaling pathway

作　　者：赵慧 陈文文 朱丽萍 葛鸿 ZHAO Hui;CHEN Wenwen;ZHU Liping;GE Hong(Department of Endocrinology,Qingdao Hospital of Traditional Chinese Medicine(Hiser Hospital),Qingdao 266033,China;Department of Neurosurgery,Qingdao Hospital of Traditional Chinese Medicine(Hiser Hospital),Qingdao 266033)

机构地区：[1]青岛市中医医院(市海慈医院)内分泌科,山东青岛266033 [2]青岛市中医医院(市海慈医院)神经外科,山东青岛266033

出　　处：《中国比较医学杂志》2022年第3期78-86,共9页Chinese Journal of Comparative Medicine

摘　　要：目的基于TLR2/NF-κB信号通路研究1,25(OH)_(2)D_(3)对实验性自身免疫性甲状腺炎大鼠的保护作用机制。方法将大鼠随机分为对照组、模型组、硒酵母片对照组和1,25(OH)_(2)D_(3)低、中、高剂量组。除对照组外,其余大鼠采用皮下注射甲状腺球蛋白(PTg)建立自身免疫性甲状腺炎大鼠模型,1,25(OH)_(2)D_(3)低、中、高剂量组分别给予腹腔注射0.5、1.0、1.5μg/kg 1,25(OH)_(2)D_(3)注射剂,对照组和模型组注射等量蒸馏水,硒酵母片对照组注射等量硒酵母混悬液(每天1次),连续4周。观察大鼠甲状腺组织变化,检测大鼠甲状腺功能因子、血清炎性因子、甲状腺自身抗体含量及TLR2/NF-κB信号通路相关蛋白水平及基因表达量。结果与模型组大鼠比较,1,25(OH)_(2)D_(3)各组大鼠血清游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)及促甲状腺激素(TSH)水平、甲状腺球蛋白抗体(TGAb)、甲状腺过氧化物酶抗体(TPOAb)、白细胞介素-6(IL-6)、白细胞介素-12(IL-12)、肿瘤坏死因子-α(TNF-α)及甲状腺组织TLR2、MyD88、TRAF-6和NF-κB mRNA和蛋白表达均不同程度降低,而白细胞介素-10(IL-10)不同程度增加,高剂量1,25(OH)_(2)D_(3)组与模型组差异具有统计学意义(P<0.05)。结论1,25(OH)_(2)D_(3)对自身免疫性甲状腺炎大鼠的甲状腺功能有一定的改善作用,并能提高自身免疫抗体水平,其机制可能与1,25(OH)_(2)D_(3)抑制TLR2/NF-κB信号通路活性,从而调控IL-6、IL-10、IL-12和TNF-α等炎症因子释放有关。Objective To study the protective mechanism of 1,25(OH)_(2)D_(3) in experimental autoimmune thyroiditis rats based on the TLR2/NF-κB signaling pathway.Methods Rats were randomly divided into control,model,and selenium yeast tablet control groups,and 1,25(OH)_(2)D_(3) low,medium and high dose groups.Except for the control group,the rats were injected subcutaneously with thyroglobulin(PTg)to establish an autoimmune thyroiditis model.The low,medium and high dose groups of 1,25(OH)_(2)D_(3) were injected intraperitoneally with 0.5,1.0 and 1.5μg/kg 1,25(OH)_(2)D_(3),the control and model groups were injected with the same amount of distilled water and selenium yeast tablets,and the control group was injected with the same amount of selenium yeast suspension(once a day)for 4 weeks.Thyroid function factors,serum inflammatory factors,thyroid autoantibodies,TLR2/NF-κB signaling pathway-related protein levels,and gene expression were analyzed.Results Compared with autoimmune thyroiditis rats,serum free thyroid glycine,free thyroxine,thyroid-stimulating hormone,thyroglobulin antibody,and thyroid peroxidase antibody,and interleukin(IL)-6,IL-12,tumor necrosis factorα(TNF-α),thyroid tissue TLR2,MyD88,TRAF-6 and NF-κB mRNA and protein expression were reduced,and IL-10 was increased in 1,25(OH)_(2)D_(3) group rats.The difference between high dose 1,25(OH)_(2)D_(3) and model groups was statistically significant(P<0.05).Conclusions 1,25(OH)_(2)D_(3) improves the thyroid functions of rats with autoimmune thyroiditis and increases the level of autoimmune antibodies.The mechanism may be related to inhibition of the TLR2/NF-κB signaling pathway by 1,25(OH)_(2)D_(3),which regulates the release of inflammatory factors such as IL-6,IL-10,IL-12 and TNF-α.

关 键 词：1 25(OH)_(2)D_(3) 自身免疫甲状腺炎 大鼠 TLR2 NF-ΚB 

分 类 号：R-33[医药卫生]