在急性心肌梗塞后,下丘脑中催产素神经元驱动的心脏保护的结果
Kathryn J Schunke1,2, Jeannette Rodriguez3, Jhansi Dyavanapalli4
1Department of Biomedical Engineering, George Washington University, Suite 5000 Science and Engineering Hall, 800 22nd Street NW, Washington, DC, 20052, USA. kschunke@hawaii.edu.
Basic research in cardiology
|October 6, 2023
概括
副腹腔内核中催产素神经元的化学遗传激活在心肌梗塞 (MI) 后保护心脏. 这种方法通过刺激副交感神经系统来提高生存率并减少心律失常.
科学领域:
- 神经科学是一个神经科学.
- 心脏病学 心脏病学
- 分子生物学分子生物学
背景情况:
- 自主失衡在心血管疾病中很常见,例如心肌梗塞 (MI).
- 目前基于设备的阴道刺激对于慢性疾病是有效的,但急性心脏病发作缺乏快速,非侵入性的方法.
- 下丘脑的副腹腔核 (PVN) 含有催产素 (OXT) 和谷氨酸联合释放的神经元,这些神经元激发心神经元 (CVN).
研究的目的:
- 调查PVN-OXT神经元的化学遗传激活是否可以在MI后立即提供心脏保护.
- 探索针对PVN-OXT网络用于早期心脏病发作治疗的治疗潜力.
主要方法:
- 新生小鼠被移植到PVN-OXT神经元中,以表达DREADDs (仅由设计者药物激活的设计者受体).
- 在6周大的老鼠中诱导心肌梗塞 (MI),随后用克洛扎-N-氧化物激活DREADD.
- 进行了补丁电生理学,生存分析,三色蓝色染色,海马测定和心肌转录组分析.
主要成果:
- 化学遗传激活显著增加了从PVN-OXT神经元到CVN控制核的刺激性神经传递.
- 治疗改善了生存率,减少了炎症和纤维化,增强了线粒体功能,并且明显减少了心室的发生率.
- 转录组分析显示,在接受治疗的动物中,保留了有益的信号通路,例如肌肉蛋白受体激活.
结论:
- 在大鼠模型中,PVN-OXT网络的化学遗传激活在心脏病发作后提供了显著的心脏保护.
- 这种策略有效地刺激了副交感通路,改善了心脏功能和存活率.
- PVN-OXT网络代表了急性心脏病发作管理的有前途的治疗目标.
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