基于SOCS1\3\JAK-STATS信号通路探讨软坚消瘿颗粒治疗肝郁脾虚型桥本甲状腺炎模型大鼠的实验研究

Experimental Study of Ruanjian Xiaoying Granules(软坚消瘿颗粒)in Treatment of Hashimoto's Thyroiditis Model Rats with Liver Stagnation and Spleen Deficiency Based on SOCS1\3\JAK-STATS Signaling Pathway

目的探究软坚消瘿颗粒对肝郁脾虚型桥本甲状腺炎(Hashimoto's thyroiditis,HT)大鼠甲状腺组织SOCS1\3\JAK-STATS信号通路表达的影响。方法SD大鼠40只,随机取10只作为正常对照组,剩余大鼠采用高碘饮水与皮下注射甲状腺球蛋白联合方案建立桥本甲状腺炎大鼠模型,通过慢性束缚应激、过度疲劳、饮食失节复合方法建立肝郁脾虚大鼠模型。模型复制成功后,随机分为模型对照组(n=10)、雷公藤多苷片组(n=10)以及软坚消瘿颗粒组(n=10)。正常对照组给予常规饲养,模型对照组予以蒸馏水2 mL,雷公藤多苷片组给予雷公藤多苷片9.45 mg/kg,软坚消瘿颗粒组给予软坚消瘿颗粒16.17 g/kg,各组干预时间为8周。干预结束后比较各组大鼠一般情况、HE染色情况、甲状腺功能指标、SOCS1\3\JAK-STATS相关蛋白表达情况。结果实验过程中无大鼠死亡,与模型组相比,软坚消瘿颗粒组大鼠血清TPOAb、TGAb、FT3、FT4水平较低,TSH水平较高(P<0.05);与雷公藤多苷片组相比,软坚消瘿颗粒组大鼠血清TPOAb、TGAb、FT3、FT4水平较低(P<0.05),TSH水平较高(P<0.05)。与模型组相比,软坚消瘿颗粒组大鼠SOCS1、SOCS2、p-JAK2、p-STAT1蛋白表达水平较高(P<0.05);与雷公藤多苷片组相比,软坚消瘿颗粒组大鼠SOCS1、SOCS2、p-JAK2、p-STAT1蛋白表达水平较高(P<0.05)。结论软坚消瘿颗粒能够有效改善肝郁脾虚型HT大鼠的甲状腺功能,提高组织SOCS1、SOCS3表达水平,抑制炎性物质传导,推测与JAK-STST信号通路异常激活有关。

Objective To investigate the effect of Ruanjian Xiaoying Granules(软坚消瘿颗粒)on the expression of SOCS1\3\JAK-STATS signaling pathway in thyroid tissue of liver stagnation and spleen deficiency type of Hashimoto's thyroiditis(HT)rats.Methods Among Forty SD rats,10 were randomly selected as normal control group.The remaining rats were treated with high iodine drinking water combined with subcutaneous injection of thyroglobulin to establish the rat model of HT and the rat model of liver stagnation and spleen deficiency was established by chronic restraint stress,excessive fatigue and diet failure.After successful model replication,the rats were randomly divided into model control group(n=10),Tripterygium Wilfordii Polyglycoside Tablet group(n=10)and Ruanjian Xiaoying Granules group(n=10).The normal control group was given conventional feeding,the model control group was given 2 mL distilled water,the Tripterygium Wilforgium Polyside Tablet group was given 9.45 mg/kg Tripterygium Wilforgium Polyside Tablet and the Ruanjian Xiaoying Granules group was given 16.17 g/kg Ruanjian Xiaoying Granules.The intervention time of each group was 8 weeks.After the intervention,the general condition,HE staining,thyroid function indexes and SOCS1\3\JAK-STATS related protein expressions were compared among the groups.Results No rats died during the experiment.Compared with those of the model group,the serum levels of thyroid peroxidase antibody(TPOAb),anti thyroglobulin antibody(TGAb),free triiodothyronine(FT3)and free thyroxine(FT4)of rats in the Ruanjian Xiaoying Granules group were lower,and the thyrotropin(TSH)level was higher(P<0.05).Compared with those of the Tripterygium Wilfordii Polyside Tablet group,the serum levels of TPOAb,TGAb,FT3 and FT4 in Ruanjian Xiaoying Granules group were lower(P<0.05),and the serum levels of TSH were higher(P<0.05).Compared with those of the model group,the protein expression levels of SOCS1,SOCS2,p-JAK2 and p-STAT1 in the Ruanjian Xiaoying Granules group were higher(P<0.05).Compared with those of the Tripterygium Wilfordii Polyglycoside Tablet group,the protein expression levels of SOCS1,SOCS2,p-JAK2 and p-STAT1 in Ruanjian Xiaoying Granules group were higher(P<0.05).Conclusions Ruanjian Xiaoying Granules can effectively improve the thyroid function of HT rats with liver stagnation and spleen deficiency,increase the expression levels of SOCS1 and SOCS3 and inhibit the conduction of inflammatory substances,which may be related to the abnormal activation of JAK-STST signaling pathway.