课题基金基金详情
Tubulin蛋白可逆性解离介导的钙稳态再平稳对急性炎症相关房颤的保护作用及机制研究
结题报告
批准号:
82000322
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
左嵩
依托单位:
学科分类:
心电活动异常与心律失常
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
左嵩
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中文摘要
急性炎症是心房颤动(房颤)的重要诱发因素,针对急性炎症的上游靶向治疗在房颤防治中至关重要。心脏外科术后房颤是急性炎症相关房颤的典型代表,研究显示术前给予秋水仙碱可大幅降低房颤发生率及发作时程,缩短住院及康复时间。然而,单一的抗炎机制并不足以解释其抗心律失常效应。前期研究证实急性炎症可造成心房细胞内钙紊乱并增加致心律失常性触发活动;而后者是急性房颤发生进展的重要机制。结合微管Tubulin蛋白可逆性解离对钙稳态的调控效应,课题组提出Tubulin蛋白可逆性解离介导的心房肌细胞内钙调控可能是秋水仙碱抗心律失常效应的潜在机制。本研究拟通过小鼠急性炎症模型,采用电生理、细胞荧光成像及分子生物学等技术,从整体、组织和细胞三个层次围绕心房细胞内钙转运及心房电重构进行研究,阐明Tubulin蛋白可逆性解离介导的钙稳态再平稳对房颤保护作用的新的分子机制,为房颤治疗的上游预防性策略提供理论依据。
英文摘要
Acute inflammation is an important predisposing factor of atrial fibrillation (AF), and upstream targeted therapy for acute inflammation is very important in the prevention and treatment of AF. Post-operative Atrial fibrillation is a typical representative of acute inflammation-related atrial fibrillation. The current clinical trial showed that colchicine could significantly reduce the incidence of atrial fibrillation and the duration of the attack, shorten the time of hospitalization and rehabilitation. However, a single anti-inflammatory mechanism is not enough to explain its antiarrhythmic effect. Previous studies have confirmed that acute inflammation can cause calcium disorder in atrial cells and increase arrhythmia triggering activities, which is an essential mechanism of the development of acute atrial fibrillation. Based on the fact that the reversible dissociation of microtubule tubulin has a regulatory effect on calcium homeostasis, we speculate that the reversible dissociation of tubulin protein in atrial cardiomyocytes may be a potential mechanism for the antiarrhythmic effect of colchicine. In this study, we first set up a mouse model of acute inflammation. Then, we make use of electrophysiology, cell fluorescence imaging, and molecular biology to study the calcium handling and electrical remodeling of the atrium from the whole, tissue, and cell levels. This project will elucidate a novel molecular mechanism for the protective effect of calcium homeostasis mediated by reversible dissociation of Tubulin protein on atrial fibrillation, and provide a theoretical basis for upstream preventive strategies for AF treatment.
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DOI:--
发表时间:2021
期刊:临床心血管病杂志
影响因子:--
作者:薄小雯;左嵩;何柳;黎旭;吴嘉慧;桑才华;龙德勇;杜昕;董建增;马长生
通讯作者:马长生
DOI:10.3760/cma.j.cn112148-20210113-00039
发表时间:2021
期刊:中华心血管病杂志
影响因子:--
作者:左嵩;桑才华;龙德勇;薄小雯;赖一炜;李梦梦;何柳;赵欣;李松南;蒋晨曦;汤日波;杜昕;董建增;马长生
通讯作者:马长生
DOI:10.3760/cma.j.cn112148-20210419-00351
发表时间:2022-03-24
期刊:Zhonghua xin xue guan bing za zhi
影响因子:--
作者:Bo, X W;Zuo, S;Ma, C S
通讯作者:Ma, C S
国内基金
海外基金