Circulating low thyroid hormone levels are considered to be independent risk factor in patients with heart failure and increased mortality.Thyroid hormone-thyroid hormone receptor axis function gradually weakened with the increase of age, the elderly population multiple subclinical hypothyroidism syndrome.Autophagic death often appeared in the myocardial ischemia reperfusion injury, myocardial infarction and heart failure and other pathological process, excessive autophagy and Caspase3 mediated cleavage of Beclin-1 can increase myocardial cell death.For our previous work has demonstrated that thyroid protection of ischemic myocardium and the regulation of BCL-2 expression, the T3 was found to inhibit the myocardial autophagy, and thyroid hormone-thyroid hormone receptor alpha1 axis through the regulation of Beclin-1 combined with BCL-2 and PI3K-mTOR-Akt pathway is considered to be the main mechanism, we planned to use in heart failure rats in vivo and cultured primary myocardial cells in vitro,study on thyroid hormone effect on pathological myocardial autophagic death and its regulation mechanism, and to provide new ideas for clinical treatment of heart disease.
循环低甲状腺素水平被认为是心衰患者增加病死率的独立风险因子。甲状腺素-甲状腺素受体轴功能随着年龄增长而逐步减弱,中老年人群多发亚临床甲状腺功能低下综合征。心肌缺血再灌注损伤、心梗和心衰等病理过程中常出现自噬相关性死亡,心肌过度自噬和caspase3剪切Beclin-1均可增加心肌细胞死亡。申请者前期工作证明甲状腺素保护缺血心肌并调控BCL-2表达,预实验发现T3抑制心肌自噬,而甲状腺素-甲状腺素受体alpha1轴通过调控Beclin-1与BCL-2结合和PI3K-mTOR-Akt途径被认为是主要潜在机制,我们拟采用心衰大鼠在体实验和离体培养原代心肌细胞探讨甲状腺素对病理心肌自噬相关性死亡的作用及其调控机制,为临床心脏疾病治疗提供新的思路。
{{i.achievement_title}}
数据更新时间:2023-05-31
甘丙肽对抑郁症状的调控作用及其机制的研究进展
氧化应激与自噬
血管内皮细胞线粒体动力学相关功能与心血管疾病关系的研究进展
栀子苷对RAW264.7细胞胞饮和噬菌功能双向调节作用的初步观察
小鼠髓样细胞触发受体-2基因小发卡状RNA慢病毒载体构建
NO介导甲状腺素调节大鼠卵泡发育机制的研究
促甲状腺素(TSH)受体及其抗体的研究
胎盘甲状腺素受体信号介导拟除虫菊酯诱发胎儿生长受限的机制
垂体-甲状腺轴起源探索:文昌鱼促甲状腺素β亚基及其受体的相互作用和功能鉴定