摘要
目的基于PKA靶点研究温阳开郁方对甲状腺功能减退大鼠的抗抑郁机制。方法采用丙基硫氧嘧啶灌胃法制造甲状腺功能减退大鼠模型。将SD大鼠随机分为正常组、模型组、温阳开郁方低剂量组、高剂量组、甲状腺素组、H-89组、H-89组+高剂量组。分别给予温阳开郁方低、高剂量7.56g·kg^(-1)·d^(-1)和15.12g·kg^(-1)·d^(-1),甲状腺素4.5μg·kg^(-1)·d^(-1),连续灌胃28d作为药物干预,以H-89组2.0mg·kg^(-1)·d^(-1)腹腔注射作为PKA阻断干预。ELISA法测治疗前后血清三碘甲状腺原氨酸(T3)、四碘甲状腺原氨酸(T4)、促甲状腺激素(TSH)和治疗后脑组织cAMP含量;Western blot法测甲状腺组织促甲状腺激素受体(TSHR)和脑组织p-PKA、PKA、p-CREB、CREB、BDNF蛋白表达;HE染色观察大鼠海马组织病理变化。结果与模型组比较,温阳开郁方干预大鼠强迫游泳实验不动时间缩短(P<0.01),糖水偏好度增加(P<0.01),血清TSH浓度降低伴血清T3、T4浓度提高(P<0.01),甲状腺组织TSHR表达减少(P<0.01);伴脑组织cAMP、p-PKA、PKA、p-CREB、CREB、BDNF蛋白表达增加(P<0.05)。结论温阳开郁方是通过促进TSH与TSHR结合,改善大鼠血清甲状腺功能,增加cAMP含量以激活PKA靶点,上调CREB/BDNF蛋白表达,促进神经修复以实现其抗抑郁的作用。
Objective To investigate the antidepressant mechanism of Wenyang Kaiyu Decoction(温阳开郁方,WYKYD)in hypothyroidism 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)concentration,while the levels of T3 and T4 were elevated(P<0.01).Additionally,the expression of TSHR in the thyroid tissues were increased(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-regulating the protein expressions of CREB/BDNF,and promoting the neural repair.
作者
吴春岚
王长德
陆逸莹
刘笑迎
李红
WU Chunlan;WANG Changde;LU Yiying;LIU Xiaoying;LI Hong(Shanghai Hospital of Integrated Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chi-nese Medicine,Shanghai 200082,China;Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China)
出处
《时珍国医国药》
北大核心
2025年第15期2833-2839,共7页
JOURNAL OF LI-SHIZHEN TRADITIONAL CHINESE MEDICINE
基金
国家中医优势专科建设项目(20240511)
上海中医药大学海外中心人才培养计划(RCPY008)
第三批全国优秀中医临床人才研修项目培养(RCPYJ0013)。
