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目的探讨异基因骨髓间充质干细胞(BM-MSC)对实验性自身免疫性甲状腺炎(EAT)的治疗作用及其机制。方法利用猪甲状腺球蛋白和弗氏佐剂免疫C57BL/6小鼠,制备EAT小鼠模型。BM-MSC干预组小鼠在建模同时尾静脉输注同源BM-MSC,每只3×105,每周1次,共4次。所有小鼠均在免疫后28 d处死,分离甲状腺组织,石蜡切片、HE染色后进行病理学分析;分离血清,放射免疫分析法检测甲状腺球蛋白抗体(TgAb)、甲状腺微粒体抗体(TmAb)、甲状腺过氧化物酶抗体(TPOAb)、总3,5,3’,5’-四碘甲腺原氨酸(TT4)、总3,5,3’-三碘甲腺原氨酸(TT3)、干扰素γ(IFN-γ)和白细胞介素10(IL-10)水平。结果 1与正常对照组比较,模型组小鼠TgAb,TmAb和TPOAb均明显增高,TT4水平明显降低(P<0.05),TT3水平无明显差异,甲状腺组织破坏明显,提示成功建立EAT小鼠模型。2正常对照组甲状腺组织未见淋巴细胞浸润;模型组甲状腺组织淋巴细胞浸润明显;BM-MSC干预组可见甲状腺组织淋巴细胞浸润,浸润程度较模型组减轻。3与正常对照组相比,模型组血清中TgAb,TmAb,TPOAb和IFN-γ水平增高,IL-10水平降低(P<0.05);BM-MSC干预组与模型组相比,血清中TgAb,TmAb和TPOAb水平明显降低,TT4水平明显升高(P<0.05),TT3水平无明显差异,IFN-γ表达水平降低,IL-10表达水平增高(P<0.05)。结论 BM-MSC对EAT具有一定的治疗作用,其机制有可能与其调节辅助性T细胞(Th)1/Th2免疫平衡有关。
Objective To investigate the therapeutic effect and mechanism of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) on experimental autoimmune thyroiditis (EAT). Methods C57BL / 6 mice were immunized with porcine thyroglobulin and Freund’s adjuvant to prepare EAT mouse model. BM-MSC intervention group mice were injected with tailor-made BM-MSCs 3 × 105, once a week for 4 times. All mice were sacrificed at 28 days after immunization. Thyroid tissues and paraffin sections were isolated and histopathologically analyzed. The serum was separated and the levels of thyroglobulin antibody (TGAb) and thyroid microsomal antibody (TmAb) were detected by radioimmunoassay. Thyroid peroxidase antibody (TPOAb), total 3,5,3 ’, 5’-tetraiodothyronine (TT4), total 3,5,3’-triiodothyronine (TT3) , Interferon gamma (IFN-gamma) and interleukin 10 (IL-10) levels. Results Compared with the normal control group, the TgAb, TmAb and TPOAb in model group were significantly increased, the level of TT4 was significantly decreased (P <0.05), the level of TT3 was not significantly different, and the destruction of thyroid tissue was obvious, suggesting that EAT mouse model was successfully established. There was no lymphocytic infiltration in the thyroid tissue in the normal control group. Lymphocyte infiltration was obvious in the thyroid tissue of the model group. Lymphocyte infiltration of the thyroid tissue was observed in the BM-MSCs intervention group. Compared with the normal control group, the serum levels of TgAb, TmAb, TPOAb and IFN-γ in the model group increased and the level of IL-10 decreased (P <0.05). Compared with the model group, the levels of TgAb, TmAb and TPOAb levels were significantly decreased, TT4 level was significantly increased (P <0.05), TT3 level was no significant difference, IFN-γ expression decreased, IL-10 expression increased (P <0.05). Conclusion BM-MSCs may have a therapeutic effect on EAT, and its mechanism may be related to its regulation of immune balance of Th1 / Th2.