石杉碱甲对自身免疫性甲状腺炎小鼠的保护作用  

Protective effect of huperzine A on mice with autoimmune thyroiditis

作　　者：李智奇 王佑权 代微 LI Zhiqi;WANG Youquan;DAI Wei(Department of Thyroid and Breast Surgery,Longhua District People's Hospital of Shenzhen City,Shenzhen 518109,China;Hepingli Community Health Service Center,Longhua District People's Hospital of Shenzhen City)

机构地区：[1]深圳市龙华区人民医院甲乳外科,深圳518109 [2]深圳市龙华区人民医院和平里社区健康服务中心

出　　处：《山西医科大学学报》2025年第1期36-42,共7页Journal of Shanxi Medical University

基　　金：深圳市龙华区医疗卫生机构区级科研项目(2023072)。

摘　　要：目的 探讨石杉碱甲对自身免疫性甲状腺炎小鼠的保护作用及其机制。方法 40只雌性C57BL/6小鼠随机分为空白对照组、模型组、石杉碱甲低剂量组和石杉碱甲高剂量组,每组10只。除空白对照组外,其他组小鼠采用皮下多点注射猪甲状腺球蛋白联合高碘水的方法构建自身免疫性甲状腺炎模型。造模后,石杉碱甲低剂量组和高剂量组分别以0.05 mg/(kg·d)和0.2 mg/(kg·d)腹腔注射石杉碱甲注射液4周,空白对照组和模型组小鼠腹腔注射等量生理盐水。取材后检测各组小鼠血清甲状腺球蛋白抗体(TGAb)、甲状腺过氧化物酶抗体(TPOAb)、促甲状腺激素(TSH)、干扰素γ(IFN-γ)、肿瘤坏死因子α(TNF-α)和白介素10(IL-10)的水平;HE染色法观察甲状腺组织病理学变化;Western blot法和免疫组化法检测甲状腺组织Toll样受体4(TLR4)、核因子-κB p65(NF-κB p65)、磷酸化NF-κB p65(p-NF-κB p65)和黑素瘤缺乏因子2(AIM2)蛋白的表达水平。结果与空白对照组比较,模型组血清TGAb、TPOAb、IFN-γ、TSH和TNF-α水平明显升高(P<0.01),而IL-10水平明显降低(P<0.001),甲状腺组织中可见大量炎症细胞浸润,甲状腺组织中TLR4、p-NF-κB p65和AIM2蛋白表达水平明显上调(P<0.001)。与模型组比较,石杉碱甲低剂量组和高剂量组血清TGAb、TPOAb、IFN-γ、TSH和TNF-α水平显著降低(P<0.01),IL-10水平升高(P<0.01),甲状腺组织炎症细胞浸润减少,甲状腺组织TLR4、p-NF-κB p65和AIM2蛋白的表达水平下调(P<0.01)。与石杉碱甲低剂量组比较,石杉碱甲高剂量组血清TGAb、TPOAb、IFN-γ、TSH和TNF-α水平显著降低(P<0.01),IL-10水平升高(P<0.01),甲状腺组织炎症细胞浸润减少,甲状腺组织中TLR4、p-NF-κB p65和AIM2蛋白的表达水平下调(P<0.05)。结论 石杉碱甲通过调控TLR4/NF-κB/AIM2信号通路抑制炎症,从而改善自身免疫性甲状腺炎。Objective To investigate the protective effect and mechanism of huperzine A on mice with autoimmune thyroiditis.Methods Forty female C57BL/6 mice were randomly divided into blank control group,model group,huperzine A low-dose group and huperzine A high-dose group,with 10 mice in each group.The autoimmune thyroiditis model was constructed by subcutaneous multi-point injection of porcine thyroglobulin combined with high-iodine water in model group,huperzine A low-dose group and huperzine A high-dose group.After the modeling,the mice in huperzine A low-dose group and high-dose group were intraperitoneally injected with 0.05 mg/(kg.d)and 0.2 mg/(kg.d)huperzine A injection for 4 weeks,respectively,and the mice in blank control group and model group were intraperitoneally injected with the same amount of normal saline.Serum levels of thyroglobulin antibody(TGAb),thyroid peroxidase antibody(TPOAb),thyroid stimulating hormone(TSH),interferonγ(IFN-γ),tumor necrosis factor-α(TNF-α)and inter-leukin 1(IL-10),and the histopathological changes of thyroid gland were observed by HE staining.The expression levels of TLR4,NF-κB p65,p-NF-κB p65 and AIM2 in thyroid tissues were detected by Western blot and immunohistochemistry.Results Compared with blank control group,serum levels of TGAb,TPOAb,IFN-γ,TSH and TNF-αwere significantly increased in model group(P<0.01),while IL-10 level was significantly decreased(P<0.001),a large number of inflammatory cells infiltrated the thyroid tissue,and the expression levels of TLR4,p-NF-κB p65 and AIM2 in thyroid tissue were significantly upregulated(P<0.001).Compared with model group,serum levels of TGAb,TPOAb,IFN-γ,TSH and TNF-αwere significantly decreased in huperzine A low-dose group and huperzine A high-dose group(P<0.01),serum IL-10 level was increased(P<0.01),the inflammatory cell infiltration in thyroid tissue was decreased,and the expression levels of TLR4,p-NF-κB p65 and AIM2 in thyroid tissue were downregulated(P<0.01).Compared with huperzine A low-dose group,the levels of

关 键 词：石杉碱甲 自身免疫性甲状腺炎 小鼠 TLR4/NF-κB/AIM2信号通路 炎症 桥本氏甲状腺炎 

分 类 号：R581.4[医药卫生—内分泌]