时珍国医国药2025，Vol.36Issue(15)：2833-2839,7.DOI:10.70976/j.1008-0805.SZGYGY-2025-1506
基于PKA靶点探讨温阳开郁方对甲状腺功能减退大鼠的抗抑郁机制
To investigate the antidepressant mechanism of Wenyang Kaiyu Decoction(温阳开郁方)in hy-pothyroid rats based on PKA targets
摘要
Abstract
Objective To investigate the antidepressant mechanism of Wenyang Kaiyu Decoction(温阳开郁方,WYKYD)in hypothy-roidism rats based on the PKA targets.Methods The hypothyroid rat model was established via gavage with propylthiouracil.The SD rats were randomly divided into the normal group,model group,low/high-dose groups,thyroxine group,H-89 group,and H-89+high-dose group.The medication interventions were administered with WYKYD at low-dose and high-dose of 7.56 g·kg-1·d-1 and 15.12 g·kg-1·d-1,respectively,along with thyroxine at 4.5μg·kg-1·d-1,via gavage for consecutive 28 days.Additionally,H-89 at 2.0mg·kg-1·d-1 was injected intraperitoneally as the blocking intervention of PKA.Serum concentrations of T3,T4,and TSH,as well as brain protein content of cAMP,were measured using ELISA.The protein expressions of p-PKA,PKA,p-CREB,CREB,and BDNF in the brain tissues were assessed using Western blot(WB).Pathological changes in the hippocampal tissues were observed using HE staining.Results Compared with the model group,the rats treated with WYKYD exhibited a significantly shortened swimming immobility time(P＜0.01),an increased sucrose preference(P＜0.01),and a reduction in thyroid stimulating hormone(TSH)con-centration,while the levels of T3 and T4 were elevated(P＜0.01).Additionally,the expression of TSHR in the thyroid tissues were in-creased(P＜0.01).Simultaneously,the protein expressions of cAMP,p-PKA,PKA,p-CREB,CREB,and BDNF in the brain were significantly increased(P＜0.05).Conclusion WYKYD exerts its antidepressant effects through strengthening the binding of TSH to TSHR,improving the serum thyroid hormone levels in rats,increasing cAMP content to activate the PKA signaling pathway,up-reg-ulating the protein expressions of CREB/BDNF,and promoting the neural repair.关键词
甲状腺功能减退/抗抑郁/PKA/H-89Key words
Hypothyroidism/Antidepressant/PKA/H-89分类
医药卫生引用本文复制引用
吴春岚,王长德,陆逸莹,刘笑迎,李红..基于PKA靶点探讨温阳开郁方对甲状腺功能减退大鼠的抗抑郁机制[J].时珍国医国药,2025,36(15):2833-2839,7.基金项目
国家中医优势专科建设项目(20240511) （20240511）
上海中医药大学海外中心人才培养计划(RCPY008) （RCPY008）
第三批全国优秀中医临床人才研修项目培养(RCPYJ0013) （RCPYJ0013）
