二甲双胍治疗桥本甲状腺炎作用机制的初步探讨  

Preliminary investigation of the mechanism of action of metformin in the treatment of Hashimoto′s thyroiditis

作　　者：陈光敏 周厚地 蒋鹏 王娟 陈其谋 Chen Guangmin;Zhou Houdi;Jiang Peng;Wang Juan;Chen Qimou(Dept of Endocrinology, University-Town Hospital of Chongqing Medical University,Chongqing 401331)

机构地区：[1]重庆医科大学附属大学城医院内分泌科,重庆401331

出　　处：《安徽医科大学学报》2022年第6期991-997,共7页Acta Universitatis Medicinalis Anhui

基　　金：重庆市教育委员会科学技术研究项目(编号:KJQN202-000447)。

摘　　要：目的 初步探讨二甲双胍治疗桥本甲状腺炎的作用机制。方法 选择健康SD雌性大鼠45只,随机分为空白组、模型组、二甲双胍组,采用高碘水联合甲状腺球蛋白与弗氏佐剂混合免疫注射法模拟桥本甲状腺炎大鼠模型。造模成功后,空白组及模型组予以0.9%氯化钠溶液灌胃,二甲双胍组按300 mg/kg二甲双胍灌胃,连续给药4周,处死各组大鼠并取样。采用ELISA测定血清甲状腺功能指标(TSH、T3、T4、TGAb、TPOAb)及甲状腺组织炎性因子(TNF-α、IL-10、IL-6、IL-12)水平;HE染色观察甲状腺组织病理变化;TUNEL荧光染色检测甲状腺组织细胞凋亡;免疫组化检测甲状腺组织中Fas、Fas-L表达;Western blot测定甲状腺组织中Fas、Fas-L、FADD、cleaved caspase-3蛋白表达;qRT-PCR检测甲状腺组织中Fas、Fas-L、FADD mRNA表达。结果 与空白组比较,模型组血清中TSH、TGAb、TPOAb水平、阳性细胞比率、甲状腺组织中TNF-α、IL-6含量及Fas、Fas-L、FADD、cleaved caspase-3表达升高,血清FT3、FT4水平及甲状腺组织中IL-10、IL-12含量降低(P<0.01);与模型组比较,二甲双胍组血清中TSH、TGAb、TPOAb水平、阳性细胞比率、甲状腺组织中TNF-α、IL-6含量及Fas、Fas-L、FADD、cleaved caspase-3表达降低,血清FT3、FT4水平及甲状腺组织中IL-10、IL-12含量升高(P<0.05)。结论 二甲双胍抑制桥本甲状腺炎进展,其作用机制可能与抑制Fas/Fas-L介导的细胞凋亡途径有关。Objective To preliminarily investigate the mechanism of action of metformin in the treatment of Hashimoto′s thyroiditis.Methods Forty-five healthy SD female rats were randomly divided into control group,model group and metformin-treated group,and the rats were simulated with a model of Hashimoto′s thyroiditis by immuno-injection of high iodine water combined with thyroglobulin and Freund′s adjuvant.After successful modeling,the control group and the model group were perfused with saline,and the metformin group was administered with 300 mg/kg metformin by gavage for 4 weeks,and the rats in each group were executed and sampled.Serum thyroid function indexes(TSH,T3,T4,TGAb,TPOAb)and thyroid tissue inflammatory factors(TNF-α,IL-10,IL-6,IL-12)levels were measured by ELISA;thyroid tissue pathological changes were observed by HE staining;thyroid tissue apoptosis was detected by TUNEL fluorescence staining;thyroid tissue expression of Fas,Fas-L was detected by immunohistochemistry;the expression of Fas,Fas-L,FADD and cleaved caspase-3 in thyroid tissue was determined by Western blot;Fas,Fas-L and FADD mRNA expression in thyroid tissue was detected by qRT-PCR.Results Compared with the control group,serum levels of TSH,TGAb,TPOAb,positive cell ratio,levels of TNF-α,IL-6 and expression of Fas,Fas-L,FADD and cleaved caspase-3 in thyroid tissue were significantly higher in the model group,and serum FT3 and FT4 levels and IL-10 and IL-12 levels in thyroid tissue significantly decreased(P<0.01).Compared with the model group,serum levels of TSH,TGAb,TPOAb,positive cell ratio,TNF-αand IL-6 contents and expression of Fas,Fas-L,FADD and cleaved caspase-3 in thyroid tissue were significantly lower in the metformin group,and serum FT3 and FT4 levels and IL-10 and IL-12 contents in thyroid tissue were significantly higher(P<0.05).Conclusion Metformin inhibits the progression of Hashimoto′s thyroiditis,and its mechanism of action may be related to the inhibition of the Fas/Fas-L-mediated apoptotic pathway.

关 键 词：桥本甲状腺炎 二甲双胍 Fas/Fas-L途径 细胞凋亡 

分 类 号：R581.4[医药卫生—内分泌]