为了探究牛百叶提取物（RS）通过MST1/Hippo途径调节甲状腺细胞的增殖、凋亡和自噬在甲亢大鼠治疗中的机制，本研究使用哺乳动物不育20样激酶1（MST1）/Hippo途径。将24只大鼠根据随机数表随机分为四组：对照组、模型组、RS组和RS+Hippo抑制剂（XMU-MP-1）组（每组n=6）。除了对照组外，大鼠在21天内口服左甲状腺素钠片剂悬浮液（LST，8μg/kg）。然后，RS组大鼠口服剂量为1,350 mg/kg的RS提取物，RS+XMU-MP-1组大鼠则口服剂量为1,350 mg/kg的RS提取物和1 mg/kg的XMU-MP-1。给药15天后，观察甲状腺组织外观，并通过苏木精-伊红染色观察组织病理变化。通过透射电子显微镜观察甲状腺组织中的高尔基分泌囊泡结构。通过免疫组化检测甲状腺刺激素受体（TSH-R）的表达。使用末端脱氧核苷酸转移酶介导的封端标记法检测甲状腺组织细胞凋亡。利用实时定量引物链式反应和免疫印迹检测MST1、p-大肿瘤抑制基因1（LATS1）、p-Yes1相关转录调节因子（YAP）、增殖细胞核抗原（PCNA）、G1/S特异性环素D1（Cyclin D1）、B-细胞淋巴瘤-2（Bcl-2）、Caspase-3、微管相关蛋白轻链3 II/I（LC3-II/I）和重组人自噬相关蛋白5（ATG5）的表达。通过酶联免疫吸附测定法检测甲状腺素（T4）水平。模型组大鼠的甲状腺体积显著增加，与正常对照组比较（P<0.01）。出现了大小不均的滤泡上皮细胞、无序排列和不规则形态等病理变化。高尔基体分泌小囊泡减少，受体蛋白TSH-R和T4的表达显著增加（P<0.01），而MST1、p-LATS1、p-YAP、Caspase-3、LC3-II/I和ATG5的表达显著降低（P<0.01）。Bcl-2、PCNA和Cyclin D1的表达显著增加（P<0.01）。与模型组相比，RS提取物降低了甲状腺体积，改善了甲状腺病理情况，促进了甲状腺高尔基体内具有双层膜结构的分泌囊泡的分泌，显著抑制了TSH-R和T4水平的表达（P<0.01），上调了MST1、p-LATS1、p-YAP、Caspase-3、LC3-II/I和ATG5的表达（P<0.01），下调了Bcl-2、PCNA和Cyclin D1的表达（P<0.01）。XMU-MP-1抑制了RS提取物的干预效果（P<0.01）。RS提取物通过MST1/Hippo途径抑制甲状腺组织的增殖，促进其凋亡和自噬，用于治疗甲亢。©2023年《中国中西医结合杂志》出版社和Springer-Verlag GmbH Germany，Springer Nature的一部分。

To explore the mechanism of Radix Scrophulariae (RS) extracts in the treatment of hyperthyroidism rats by regulating proliferation, apoptosis, and autophagy of thyroid cell through the mammalian sterile 20-like kinase 1 (MST1)/Hippo pathway.Twenty-four rats were randomly divided into 4 groups according to a random number table: control, model group, RS, and RS+Hippo inhibitor (XMU-MP-1) groups (n=6 per group). Rats were gavaged with levothyroxine sodium tablet suspension (LST, 8 μ g/kg) for 21 days except for the control group. Afterwards, rats in the RS group were gavaged with RS extracts at the dose of 1,350 mg/kg, and rats in the RS+XMU-MP-1 group were gavaged with 1,350 mg/kg RS extracts and 1 mg/kg XMU-MP-1. After 15 days of administration, thyroid gland was taken for gross observation, and histopathological changes were observed by hematoxylin-eosin staining. The structure of Golgi secretory vesicles in thyroid tissues was observed by transmission electron microscopy. The expression of thyrotropin receptor (TSH-R) was observed by immunohistochemistry. Terminal-deoxynucleoitidyl transferase mediated nick end labeling assay was used to detect cell apoptosis in thyroid tissues. Real-time quantity primer chain reaction and Western blot were used to detect the expressions of MST1, p-large tumor suppressor gene 1 (LATS1), p-Yes1 associated transcriptional regulator (YAP), proliferating cell nuclear antigen (PCNA), G1/S-specific cyclin-D1 (Cyclin D1), B-cell lymphoma-2 (Bcl-2), Caspase-3, microtubule-associated proeins light chain 3 II/I (LC3-II/I), and recombinant human autophagy related 5 (ATG5). Thyroxine (T4) level was detected by enzyme-linked immunosorbent assay.The thyroid volume of rats in the model group was significantly increased compared to the normal control group (P<0.01), and pathological changes such as uneven size of follicular epithelial cells, disorderly arrangement, and irregular morphology occurred. The secretion of small vesicles by Golgi apparatus was reduced, and the expressions of receptor protein TSH-R and T4 were significantly increased (P<0.01), while the expressions of MST1, p-LATS1, p-YAP, Caspase-3, LC3-II/I, and ATG5 were significantly decreased (P<0.01). The expressions of Bcl-2, PCNA, and cyclin D1 were significantly increased (P<0.01). Compared with the model group, RS extracts reduced the volume of thyroid gland, improved pathological condition of the thyroid gland, promoted secretion of the secretory vesicles with double-layer membrane structure in thyroid Golgi, significantly inhibited the expression of TSH-R and T4 levels (P<0.01), upregulated MST1, p-LATS1, p-YAP, Caspase-3, LC3-II/I, and ATG5 expressions (P<0.01), and downregulated Bcl-2, PCNA, and Cyclin D1 expressions (P<0.01). XMU-MP-1 inhibited the intervention effects of RS extracts (P<0.01).RS extracts could inhibit proliferation and promote apoptosis and autophagy in thyroid tissues through MST1/Hippo pathway for treating hyperthyroidism.© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.