南京中医药大学学报2026，Vol.42Issue(8)：1161-1173,13.DOI:10.14148/j.issn.1672-0482.2026.1161
阳和汤改善自身免疫性甲状腺炎大鼠认知障碍的作用及机制研究
Effects and Mechanisms of Yanghe Decoction in Ameliorating Cognitive Impairment in Rats with Autoim-mune Thyroiditis
摘要
Abstract
OBJECTIVE To investigate the effects and mechanisms of Yanghe Decoction(YHD)in ameliorating cognitive dys-function associated with experimental autoimmune thyroiditis(EAT)in rats through modulation of the thyroid-brain axis.METHODS EAT was induced in female Sprague-Dawley rats by repeated immunization with porcine thyroglobulin and Freund's adjuvant,while 0.5%Lugol's iodine was supplied in drinking water.Following successful model establishment,rats received low-dose(5 g·kg⁻¹)or high-dose(15 g·kg⁻¹)YHD by gavage for 6 weeks.Serum TPOAb and TgAb were measured by ELISA.Hippocampal IL-1β,IL-6,TNF-α,and COX-2 levels were quantified.Thyroid histopathology was assessed by hematoxylin-eosin(HE)staining,and cognitive function was evaluated with the Morris water maze.Network pharmacology,molecular docking,and untargeted LC-MS/MS metabolo-mics were used to identify the bioactive components of YHD and the pathways through which it ameliorates EAT-related cognitive im-pairment.Hippocampal protein expression of epidermal growth factor receptor(EGFR),caspase-3(CASP3),tumor necrosis factor(TNF),synapsin-1,postsynaptic density protein-95(PSD-95),and glutamate ionotropic receptor AMPA type subunit 1(GluA1)was measured by Western blot.RESULTS YHD reduced thyroid lymphocytic infiltration and lowered serum TPOAb and TgAb levels in a dose-dependent manner.In the Morris water maze,YHD shortened escape latency and increased platform crossings and target-quadrant dwell time,indicating improved cognitive performance.Network pharmacology showed that intersecting targets were enriched in EGFR and insulin signaling pathways.Further molecular docking experiments demonstrated strong binding affinities between β-si-tosterol and EGFR,β-sitosterol and CASP3,quercetin and EGFR,quercetin and TNF,and kaempferol and TNF.Hippocampal metabo-lomics further revealed that YHD downregulated arachidonic acid,linoleic acid,and palmitic acid,restored docosahexaenoic acid,and corrected polyunsaturated fatty acid dysregulation.Mechanistically,compared with the model group,both low and high doses of YHD significantly reduced the expression levels of hippocampal COX-2 and its effector prostaglandin E2,inhibited the expression of IL-1β,IL-6,and TNF-α,and downregulated the protein levels of TNF,EGFR,and CASP3;ultimately,the treatment restored hippocampal protein expression of Synapsin-1,PSD-95,and GluA1,thereby maintaining synaptic function.CONCLUSION YHD alleviates cog-nitive dysfunction in EAT rats,likely by reducing thyroid autoantibodies,correcting polyunsaturated fatty acid metabolic disturbances,suppressing hippocampal inflammation,and restoring synaptic plasticity.These findings provide network pharmacology,metabolomic,and molecular evidence that YHD acts through the thyroid-brain axis to mitigate AIT-associated cognitive impairment.关键词
阳和汤/自身免疫性甲状腺炎/认知障碍/突触可塑性/神经炎症Key words
Yanghe Decoction/autoimmune thyroiditis/cognitive impairment/synaptic plasticity/neuroinflammation分类
医药卫生引用本文复制引用
江亮,费宗奇,王建华,马丙娥..阳和汤改善自身免疫性甲状腺炎大鼠认知障碍的作用及机制研究[J].南京中医药大学学报,2026,42(8):1161-1173,13.基金项目
国家自然科学基金青年科学基金项目(82405404) （82405404）
江苏省中医药管理局自然科学基金(JD2023SZX03) （JD2023SZX03）
江苏省中医药研究院自然科学基金(2024YZRKXJJ02) （2024YZRKXJJ02）
