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模拟微重力会阻碍 Notch 信号通路在对抗心肌缺血再灌注损伤中的作用。

Simulated microgravity hampers Notch signaling in the fight against myocardial ischemia‑reperfusion injury.

机构信息

Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.

出版信息

Mol Med Rep. 2018 Apr;17(4):5150-5158. doi: 10.3892/mmr.2018.8489. Epub 2018 Jan 25.

Abstract

The gravitational field is an important determinant of cardiovascular function. Exposure to microgravity during spaceflight may lead to a series of maladaptive alterations in the cardiovascular system. The authors have previously demonstrated that microgravity can increase the susceptibility to myocardial ischemia‑reperfusion (IR) injury under simulated microgravity. Although Notch1 signaling protects against myocardial IR injury, whether Notch1 protects against myocardial IR injury under simulated weightlessness remains unknown. The present study is designed to investigate the role of the Notch1 receptor in myocardial IR injury under simulated weightlessness. The differences in Notch signaling expression and myocardial infarct size following myocardial IR were compared between normal rats and tail‑suspended rats that were kept in 30˚ head‑down tilt and hindlimb unloading position. The data revealed low expression levels of Notch1 receptor and its endogenous ligand Jagged1 in normal adult rat hearts. However, significantly higher expression of Notch1 was observed in the border zone compared with the infarcted area and the remote zone following myocardial IR. Notch1 expression was notably reduced in the infarcted hearts of tail‑suspended rats compared with the control group. Conversely, the myocardial infarct size was significantly increased in tail‑suspended rats compared with the control rats. In conclusion, these data suggested that the proper function of Notch signaling may be hampered under simulated microgravity.

摘要

重力场是心血管功能的重要决定因素。在太空飞行中暴露于微重力下可能导致心血管系统发生一系列适应性改变。作者先前已经证明,微重力可以增加模拟微重力下心肌缺血再灌注(IR)损伤的易感性。尽管 Notch1 信号通路可以保护心肌免受 IR 损伤,但 Notch1 是否可以保护模拟失重下的心肌免受 IR 损伤尚不清楚。本研究旨在探讨 Notch1 受体在模拟失重下心肌 IR 损伤中的作用。比较了正常大鼠和 30°头低位倾斜和后肢去负荷位尾部悬吊大鼠心肌 IR 后 Notch 信号表达和心肌梗死面积的差异。结果显示,正常成年大鼠心脏中 Notch1 受体及其内源性配体 Jagged1 的表达水平较低。然而,在心肌 IR 后,与梗死区和远隔区相比,交界区 Notch1 的表达显著升高。与对照组相比,尾部悬吊大鼠的梗死心脏中 Notch1 的表达明显降低。相反,与对照组相比,尾部悬吊大鼠的心肌梗死面积显著增加。总之,这些数据表明,在模拟微重力下 Notch 信号的正常功能可能受到阻碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5672/5865980/0c755d3b49ac/MMR-17-04-5150-g00.jpg

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