醒消丸对结节性甲状腺肿模型大鼠甲状腺细胞增殖和凋亡的影响

Effect of Xingxiao Pill (醒消丸) on Thyroid Cell Proliferation and Apoptosis in Rats with Nodular Goiter

目的:研究醒消丸对结节性甲状腺肿模型大鼠甲状腺细胞增殖和凋亡的影响。方法:采用丙基硫氧嘧啶(PTU)灌胃复制结节性甲状腺肿大鼠模型。造模成功后随机分为模型组,左甲状腺素钠片组(15.0μg/kg),醒消丸高、中、低剂量组(1.2 g/kg、0.6 g/kg、0.3 g/kg),另设对照组。给予相应药物干预6周后。检测甲状腺质量、相对质量;HE染色分析甲状腺组织的病理学变化;ELISA法检测血清中促甲状腺激素(TSH)、游离三碘甲腺原氨酶(FT3)、游离甲状腺素(FT4)水平;TUNEL染色分析甲状腺细胞的凋亡情况;Western blotting法检测增殖相关蛋白VEGF的表达水平。结果:左甲状腺素钠片组大鼠与醒消丸高、中、低剂量组大鼠甲状腺组织滤泡肿胀和增生减少,上皮细胞排列趋于规则,甲状腺上皮细胞肿胀和间质间炎症细胞浸润情况明显改善;与模型组比较,左甲状腺素钠片组、醒消丸高剂量和醒消丸低剂量组大鼠甲状腺相对质量降低(P<0.01),左甲状腺素钠片组和醒消丸高剂量组大鼠甲状腺质量显著降低(P<0.01);与模型组比较,左甲状腺素钠片组、醒消丸高剂量组和醒消丸中剂量组大鼠血清TSH水平降低(P<0.05或P<0.01),FT3水平明显升高(P<0.05),左甲状腺素钠片组及醒消丸高、中、低剂量组FT4水平明显升高(P<0.05或P<0.01);与模型组比较,醒消丸高、中剂量组大鼠甲状腺组织细胞凋亡显著升高(P<0.05);与模型组比较,左甲状腺素钠片组和醒消丸高、中剂量组大鼠甲状腺组织中VEGF蛋白相对表达量降低(P<0.01或P<0.05)。结论:醒消丸可降低结节性甲状腺肿大鼠血清中TSH的含量,升高FT3及FT4的含量,减轻结节性甲状腺肿大鼠的甲状腺组织结构改变,抑制甲状腺细胞增殖,促进甲状腺细胞凋亡。

Objective: To investigate the effect of Xingxiao pill on thyroid cell proliferation and apoptosis in rats with nodular goiter. Methods: The rat model of nodular goiter was replicated by gavage administration of propylthiouracil (PTU). After the model is successfully made, rats were randomly divided into model group, levothyroxine sodium tablets group (15.0 μg/kg), high, medium and low dose Xingxiao pill groups (1.2 g/kg, 0.6 g/kg, 0.3 g/kg), and a control group was additionally set. After 6 weeks of intervention with corresponding drugs, the weight and relative mass of thyroid tissue were measured. The pathological changes of thyroid tissue were analyzed by HE staining. The levels of thyroid-stimulating hormone (TSH), free triiodothyrogenoaminase (FT3) and free thyroxine (FT4) in serum were detected by ELISA. The apoptosis rate of thyroid cells was analyzed by TUNEL staining. The expression level of VEGF, a proliferation-related protein, was detected by Western blotting. Results: The swelling and proliferation of thyroid follicles in levothyroxine sodium tablets group, the high, medium and low dose Xingxiao pill groups was reduced. The arrangement of epithelial cells tended to be regular in levothyroxine sodium tablets group, and the high, medium and low dose Xingxiao pill groups, and the swelling of thyroid epithelial cells and the infiltration of interstitial inflammatory cells was significantly improved in levothyroxine sodium tablets group, and the high, medium and low dose Xingxiao pill groups. Compared with the model group, the relative weight of thyroid gland in levothyroxine sodium tablets group, and the high dose and low dose Xingxiao pill groups was significantly decreased (P<0.01), and the weight of thyroid gland in the levothyroxine sodium tablets group and high dose Xingxiao pill groups was significantly reduced (P<0.01). Compared with the model group, the serum TSH levels of the levothyroxine sodium tablets group, and the high dose and medium dose Xingxiao pill groups were significantly decreased (P<0.05 or P<0.01), while the serum FT3 levels of the levothyroxine sodium tablets group, and the high dose and medium dose Xingxiao pill groups were significantly increased (P<0.01 or P<0.05). The serum FT4 levels of the levothyroxine sodium tablets group, and the high, medium and low dose Xingxiao pill groups was significantly increased (P<0.01). Compared with the model group, the apoptosis of thyroid histiocytes in the high and medium dose Xingxiao pill groups was significantly increased (P<0.05). Compared with the model group, the expression of VEGF protein in the thyroid tissue of the levothyroxine sodium tablet group, and the high and medium dose Xingxiao pill groups was significantly reduced (P<0.01 or P<0.05). Conclusion: Xingxiao pill can reduce the content of TSH, increase the content of FT3 and FT4 in the serum of nodular goiter rats, alleviate the changes in thyroid tissue structure of nodular goiter rats, inhibit thyroid cell proliferation, and promote thyroid cell apoptosis.