四逆汤药物有效组分配伍对大鼠甲状腺功能减退症的治疗作用及蛋白质组学研究

Effects of Components Compatibility of Sini Decoction on Hypothyroidism in Rats

目的:研究有效组分配伍的四逆汤对甲状腺功能减退症的治疗作用。方法:用甲状腺过氧化物酶抑制剂丙基硫氧嘧啶制备SD大鼠甲减动物模型,以有效组分配伍的四逆汤高、中、低剂量组(9.6g生药/kg、4.8g生药/kg、2.4g生药/kg)对甲减动物进行治疗。实验过程中观察动物一般状态,并定期记录各组动物的饮食、饮水量,实验结束后,测定各组动物血清甲状腺激素水平;HE染色观察各组动物甲状腺病理损伤程度;采用双向凝胶电泳技术测定血清蛋白质组学差异。结果:与空白对照组相比,模型组动物饮食饮水量明显减少,出现倦卧、耸毛等症状,T3、T4水平显著降低,TSH水平显著升高,甲状腺组织病理损伤严重;与模型对照组相比,四逆汤药物有效组分配伍组饮食饮水量升高,一般状态有所改善,2.4、4.8g/kg组可显著升高模型动物的血清T3、T4水平,降低TSH水平;四逆汤药物有效组分配伍各剂量组均可显著改善甲状腺病理损伤程度;蛋白组学研究结果表明与空白组比较,模型组有34个蛋白表达上调、67个蛋白表达下调,四逆汤有效组分配伍9.6g/kg组可将上调蛋白中的14个蛋白表达下调2倍以上,下调蛋白中的7个蛋白表达上调2倍以上。结论:四逆汤药物有效组分配伍对大鼠甲状腺功能减退症有治疗作用。

Objective： To study the effect of components compatibility of Sini decoction on hypothyroidism. Methods： The hypothyroidism model was established by the thyroid peroxidase inhibitor propylthiouracil,and high,medium and low doses of components compatibility of Sini decoction groups（9. 6 g crude drug/kg,4. 8 g crude drug/kg,2. 4 g crude drug/kg） were used to treat hypothyroidism. General statuses of animals were observed,amounts of food consumption and drinking water were regularly recorded in each group. Levels of serum thyroid hormone were determined,and the degree of thyroid pathological damage was observed by HE staining. The difference in serum proteomics was measured by two-dimensional gel electrophoresis. Results： Compared with the control group,amounts of the food intake and drinking water were significantly reduced in the model group,symptoms such as drowsiness and shrub were observed,and levels of T3,T4 were significantly reduced（P〈0. 05）,TSH level（P〈0. 05） was increased,and thyroid tissues were serious damaged. Compared with the model group,rats in components compatibility of Sini decoction group consumed more food and more water,and general statuses were improved,levels of serum T3,T4 increased（P〈0. 05） and TSH level were decreased（P〈0. 05） in the middle and high doses of groups. Degrees of pathological damage were reduced in all treatment groups. Compared with the control group,34 proteins were up-regulated and 67 proteins were down-regulated in the model group. Compared with the model group,14 proteins were down 2 times among up-regulated proteins,and 7 proteins are up 2 times among down-regulated proteins in high dose of treatment group. Conclusion： Components compatibility of Sini decoction has the good effect on hypothyroidism.