摘要
目的:探讨活血消瘿方(HXXYF)调控Notch/调节性T细胞(Treg)/辅助性T细胞17(Th17)通路对桥本甲状腺炎(HT)大鼠甲状腺功能和病理形态的影响。方法:将84只大鼠随机分为对照组(NC组)、模型组(Model组)、低剂量HXXYF组(HXXYF-L组,0.5 g/kg)、高剂量HXXYF组(HXXYF-H组,2 g/kg)、左旋甲状腺素钠组(LTSD组,0.1 mg/kg)、Jagged1(Notch激活剂)组(0.67 mg/kg Jagged1)、HXXYF-H+Jagged1组(2 g/kg+0.67 mg/kg),每组12只。除NC组外,其他组大鼠均构建HT模型。全部造模成功后,进行给药处理,1次/d,持续4周。ELISA法检测大鼠血清中游离三碘甲状腺原氨酸(FT_(3))、游离甲状腺素(FT_(4))、促甲状腺激素(TSH)、甲状腺过氧化物酶抗体(TPOAb)、甲状腺球蛋白抗体(TGAb)、白细胞介素(IL)-17、IL-10水平;流式细胞术检测大鼠外周血中Treg、Th17比例;HE染色检测大鼠甲状腺组织病理变化;Western blotting检测甲状腺组织中叉头框蛋白P3(Foxp3)、维甲酸相关孤核受体γt(RORγt)、Notch1蛋白表达。结果:与NC组比较,Model组大鼠甲状腺组织病理损伤严重,FT_(3)、FT_(4)、IL-10水平,Treg比例,Foxp3蛋白表达均降低(P<0.05),TSH、TPOAb、TGAb、IL-17水平,Th17比例,RORγt、Notch1蛋白表达均升高(P<0.05);与Model组比较,HXXYF-L组、HXXYF-H组、LTSD组大鼠甲状腺组织病理损伤均减轻,FT_(3)、FT_(4)、IL-10水平,Treg比例,Foxp3蛋白表达均升高(P<0.05),TSH、TPOAb、TGAb、IL-17水平,Th17比例,RORγt、Notch1蛋白表达均降低(P<0.05),Jagged1组对应指标变化趋势与上述相反(P<0.05);Jagged1减弱了高剂量HXXYF对HT大鼠甲状腺功能和病理形态的改善作用。结论:HXXYF可能通过抑制Notch通路来调节Treg/Th17平衡进而改善HT大鼠甲状腺功能和病理形态。
Objective:To investigate the influences of Huoxue Xiaoying Fang(HXXYF)on thyroid function and pathological morphology of Hashimoto thyroiditis(HT)rats by regulating Notch/regulatory T cell(Treg)/T helper 17 cell(Th17)pathway.Methods:A total of 84 rats were randomly divided into control group(NC group),model group,low-dose HXXYF group(HXXYF-L group,0.5 g/kg),high-dose HXXYF group(HXXYF-H group,2 g/kg),levothyroxine sodium group(LTSD group,0.1 mg/kg),Jagged1(Notch activator)group(0.67 mg/kg Jagged1),HXXYF-H+Jagged1 group(2 g/kg+0.67 mg/kg),with 12 rats in each group.Except NC group,rats in other groups were all built with HT model.After successful modeling,the drug was administered once a day for 4 weeks.The levels of free triiodothyronine(FT_(3)),free thyroxine(FT_(4)),thyroid stimulating hormone(TSH),thyroid peroxidase antibody(TPOAb),thyroglobulin antibody(TGAb),interleukin(IL)-17 and IL-10 in rat serum were detected by ELISA.The ratios of Treg and Th17 in peripheral blood of rats was detected by flow cytometry.HE staining was used to detect the pathological changes of thyroid tissue in rats.Western blotting was applied to detect the expression of forkhead box protein P3(Foxp3),retinoic acid-related orphan receptorγt(RORγt)and Notch1 proteins in thyroid tissue.Results:Compared with the NC group,the pathological damage of thyroid tissue in the Model group was severe,the levels of FT_(3),FT_(4) and IL-10,the proportion of Treg and the expression of Foxp3 protein were decreased(P<0.05),the levels of TSH,TPOAb,TGAb and IL-17,the proportion of Th17,the expression of RORγt and Notch1 protein were increased(P<0.05).Compared with the Model group,the pathological damage of thyroid tissue in HXXYF-L group,HXXYF-H group and LTSD group was reduced,the levels of FT_(3),FT_(4) and IL-10,the proportion of Treg,the expression of Foxp3 protein were increased(P<0.05),the levels of TSH,TPOAb,TGAb and IL-17,the proportion of Th17,the expression of RORγt and Notch1 protein were decreased(P<0.05),and the change trend of the corresponding indexes in Jagged1 group was opposite to the above(P<0.05).Jagged1 attenuated the effect of high-dose HXXYF on thyroid function and pathological morphology in HT rats.Conclusion:HXXYF may regulate Treg/Th17 balance by inhibiting Notch pathway to improve thyroid function and pathological morphology in HT rats.
作者
岳思恩
狄岩
陈晓珩
YUE Sien;DI Yan;CHEN Xiaoheng(Dongzhimen Hospital of Beijing University of Chinese Medicine,Beijing 100700,China)
出处
《中医药导报》
2023年第9期7-11,42,共6页
Guiding Journal of Traditional Chinese Medicine and Pharmacy
基金
北京中医药大学东直门医院创新课题(DZMKJCX-2022-012)。
