目的 探讨消癥丸对结节性甲状腺肿模型大鼠甲状腺组织结构、功能、细胞凋亡及丝裂原活化蛋白激酶（MEK）/细胞外调节蛋白激酶（ERK）信号通路的影响。方法 将SD大鼠随机分为对照组、模型组、左甲状腺素钠组、消癥丸（0.63、1.89 g/kg）组。记录大鼠体质量、甲状腺组织质量；苏木精–伊红（HE）染色观察大鼠甲状腺组织的病理变化；通过ELISA法检测大鼠血清促甲状腺激素（TSH）、游离三碘甲腺原氨酶（fT3）、游离甲状腺素（fT4）水平；TUNEL染色观察大鼠甲状腺组织细胞凋亡的情况；Western blotting及免疫组化法观察大鼠甲状腺组织凋亡相关蛋白B细胞淋巴瘤-2（Bcl-2）、Bcl-2相关X蛋白（Bax）以及MEK/ERK信号通路蛋白的表达情况。结果 与模型组相比，消癥丸（0.63、1.89 g/kg）组甲状腺质量显著降低（P＜0.001）；消癥丸1.89 g/kg组甲状腺相对质量显著降低（P＜0.001）。与模型组比较，消癥丸（0.63、1.89 g/kg）组大鼠血清TSH水平显著降低，血清中fT3、fT4水平显著升高（P＜0.001）。消癥丸1.89 g/kg组大鼠甲状腺滤泡腔内胶质显著增加，间质间炎症细胞浸润情况得到了明显改善。与模型组相比，消癥丸1.89 g/kg组Bax、Bax/Bcl-2蛋白表达显著增加，Bcl-2蛋白表达显著降低（P＜0.01、0.001）。与模型组相比，消癥丸0.63、1.89 g/kg组p-ERK/ERK和p-MEK/MEK的蛋白表达显著降低（P＜0.01、0.001）。结论 消癥丸能够抑制MEK/ERK通路，调节凋亡相关蛋白的表达，促进甲状腺细胞凋亡，从而发挥治疗结节性甲状腺肿的作用，且安全性良好。

Objective To explore the effects of Xiaozheng Pills on thyroid tissue structure, function, cell apoptosis and MEK/ERK signaling pathway in a rat model of nodular goiter. Methods SD rats were randomly divided into the control group, the model group, the levothyroxine sodium group, and the Xiaozheng Pills (0.63 and 1.89 g/kg) groups. The body weight and thyroid tissue weight of the rats were recorded, HE staining was used to observe the pathological changes of the rat thyroid tissue, the levels of serum TSH, fT, and fT4 in the rat serum were detected by ELISA. TUNEL staining was used to observe the apoptosis of thyroid tissue cells in the rats; Western blotting and immunohistochemical methods were used to observe the expression of apoptosis-related proteins Bcl-2, Bax protein, and MEK/ERK signaling pathway proteins in the rat thyroid tissue. Results Compared with the model group, the thyroid mass in the Xiaozheng Pills (0.63 and 1.89 g/kg) groups was significantly reduced (P < 0.001); the relative thyroid mass in the 1.89 g/kg Xiaozheng Pills group was also significantly reduced (P < 0.001). Compared with the model group, the serum TSH levels in the Xiaozheng Pills (0.63 and 1.89 g/kg) groups were significantly decreased, while the serum levels of fT3 and fT4 were significantly increased (P < 0.001). In the Xiaozheng Pills 1.89 g/kg group, the amount of gel in the thyroid follicular cavities significantly increased, and the infiltration of inflammatory cells in the interstitial area was significantly improved. Compared with the model group, the Bax and Bax/Bcl-2 protein expressions in the Xiaozheng Pills 1.89 g/kg group significantly increased, while the Bcl-2 protein expression significantly decreased (P < 0.01, 0.001). Compared with the model group, the protein expressions of p-ERK/ERK and p-MEK/MEK in the Xiaozheng Pills 0.63 and 1.89 g/kg groups were significantly decreased (P < 0.01, 0.001). Conclusion Xiaozheng Pills can inhibit the MEK/ERK pathway, regulate the expression of apoptosis-related proteins, promote thyroid cell apoptosis, and thereby exert a therapeutic effect on nodular goiter, with good safety.

R286.7

国家自然科学基金-青年科学基金项目C类（82500441）；江苏省自然科学青年基金项目（BK20241628）