目的 探讨白芍总苷对自身免疫性甲状腺炎（autoimmune thyroiditis，AIT）大鼠肠道菌群及肠黏膜屏障的影响。方法 SD大鼠随机分为对照组、模型组、硒酵母（36 μg/kg）组及白芍总苷低、中、高剂量（160、320、640 mg/kg）组，每组8只。采用高碘水喂养联合sc猪甲状腺球蛋白与弗氏佐剂诱导AIT大鼠模型，造模后ig相应药物，1次/d，连续6周。采用ELISA法测定各组大鼠血清中甲状腺球蛋白抗体（thyroglobulin antibodies，TGAb）、甲状腺过氧化物酶抗体（thyroid peroxidase antibodies，TPOAb）、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）和白细胞介素-10（interleukin-10，IL-10）水平；采用苏木素-伊红（HE）染色观察各组大鼠甲状腺和结肠组织病理变化；采用透射电镜（TEM）观察各组大鼠结肠黏膜紧密连接结构；采用ELISA法测定各组大鼠结肠组织分泌型免疫球蛋白A （secretory immunoglobulin A，sIgA）水平；采用Western blotting法检测各组大鼠结肠组织闭锁连接蛋白-1（zonula occludens-1，ZO-1）和闭合蛋白（Occludin）表达情况；采用16S rRNA高通量测序技术检测各组大鼠肠道菌群变化。结果 白芍总苷能够显著降低AIT大鼠血清中TGAb、TPOAb和TNF-α水平（P<0.001），显著升高血清中IL-10水平（P<0.001），减轻甲状腺滤泡损伤及结肠黏膜病变程度，改善结肠黏膜紧密连接超微结构，显著升高结肠组织中sIgA水平（P<0.05、0.01、0.001），显著升高结肠组织ZO-1和Occludin蛋白表达水平（P<0.01、0.001），降低肠道菌群生物多样性及丰度指数，显著降低厚壁菌门相对丰度（P<0.001），显著升高拟杆菌门相对丰度（P<0.001），显著升高乳酸杆菌属Lactobacillus、普雷沃氏菌属Prevotellaceae和罗姆布茨菌属Romboutsia相对丰度（P<0.05、0.001）。结论 白芍总苷可能通过调节AIT大鼠肠道菌群组成及多样性，改善肠黏膜屏障损伤，从而发挥治疗AIT的作用。

Objective To explore the effect of total glucosides of Paeonia lactiflora (TGP) on intestinal mucosal barrier and intestinal flora in rats with autoimmune thyroiditis (AIT). Methods SD rats were randomly divided into control group, model group, selenium (36 μg/kg) group, low-, medium-, high-dose TGP (160, 320, 640 mg/kg) groups. AIT rat model was established by feeding high-iodine water combined with sc porcine thyroglobulin and Freund's adjuvant, and then rats were ig drugs once daily for 6 weeks. ELISA was used to detect levels of thyroglobulin antibody (TGAb), thyroid peroxidase antibody (TPOAb), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) in serum of rats in each group; Hematoxylin-eosin (HE) staining was used to observe the pathological changes of thyroid and colon tissues of rats in each group; Transmission electron microscopy (TEM) was used to observe the tight junction structure of colon mucosa of rats in each group; ELISA was used to detect secretory immunoglobulin A (sIgA) level in colon tissue of rats in each group; Western blotting was used to detect expressions of zonula occludens-1 (ZO-1) and Occludin in colon tissue of rats in each group; 16S rRNA high-throughput sequencing technology was used to detect intestinal flora changes of rats in each group. Results TGP significantly reduced levels of TGAb, TPOAb, and TNF-α in serum of AIT rats (P < 0.001), increased IL-10 level in serum (P < 0.001), alleviated the damage of thyroid follicles and degree of colonic mucosal lesions, improved the ultrastructure of colon tight junctions, increased sIgA level in colon tissue (P < 0.05, 0.01, 0.001), increased expressions of ZO-1 and Occludin in colon tissue (P < 0.01, 0.001), reduced the biological diversity and abundance index of intestinal flora, reduced the relative abundance of firmicutes (P < 0.001), increased the relative abundance of bacteroides (P < 0.001), increased the relative abundance of Lactobacillus, Prevotellaceae and Romboutsia (P < 0.05, 0.001). Conclusion TGP may play a therapeutic role in AIT by regulating composition and diversity of intestinal flora and improving intestinal mucosal barrier damage.

R285.5

国家中医药管理局中医学术流派传承工作室建设项目（LP0117039）；湖北省卫健委中医药科研重点项目（ZY2019Z007）；湖北省自然科学基金面上项目（2019CFB800）；贵州省中医药管理局中医药、民族医药科学技术研究课题（QZYY2019024）