中文摘要：

以前的研究表明神經(jīng)元引導(dǎo)分子 netrin-1 有助于減輕心肌缺血再灌注損傷。然而，組織特異性來(lái)源和受體信號(hào)轉(zhuǎn)導(dǎo)事件仍然難以捉摸。中性粒細(xì)胞是最早對(duì)缺血性損傷做出反應(yīng)的細(xì)胞之一，可能與組織損傷或救援有關(guān)。我們發(fā)現(xiàn)心肌梗死患者血液中 netrin-1 水平升高，以及暴露于心肌缺血再灌注的小鼠。在 Ntn1loxP/loxP Lyz2 Cre+ 小鼠中發(fā)現(xiàn)選擇性增加的梗死面積和肌鈣蛋白水平，但在其他組織區(qū)室中條件性 netrin-1 缺失的小鼠中沒(méi)有發(fā)現(xiàn)。使用中性粒細(xì)胞耗竭的體內(nèi)研究確定，中性粒細(xì)胞是心肌損傷期間血液 netrin-1 升高的主要來(lái)源。最后，使用重組 netrin-1 治療的藥理學(xué)研究揭示了通過(guò)髓樣腺苷 A2b 受體的嘌呤能信號(hào)事件在介導(dǎo) netrin-1 誘導(dǎo)的心臟保護(hù)中的功能作用。這些發(fā)現(xiàn)表明，中性粒細(xì)胞來(lái)源的 netrin-1 在通過(guò)髓系腺苷 A2b 信號(hào)傳導(dǎo)減輕心肌缺血再灌注損傷中具有功能作用的自分泌信號(hào)回路。

英文摘要：

Previous studies implicated the neuronal guidance molecule netrin-1 in attenuating myocardial ischemia-reperfusion injury. However, the tissue-specific sources and receptor signaling events remain elusive. Neutrophils are among the first cells responding to an ischemic insult and can be associated with tissue injury or rescue. We found netrin-1 levels were elevated in the blood of patients with myocardial infarction, as well as in mice exposed to myocardial ischemia-reperfusion. Selectively increased infarct sizes and troponin levels were found in Ntn1loxP/loxP Lyz2 Cre+ mice, but not in mice with conditional netrin-1 deletion in other tissue compartments. In vivo studies using neutrophil depletion identified neutrophils as the main source for elevated blood netrin-1 during myocardial injury. Finally, pharmacologic studies using treatment with recombinant netrin-1 revealed a functional role for purinergic signaling events through the myeloid adenosine A2b receptor in mediating netrin-1–elicited cardioprotection. These findings suggest an autocrine signaling loop with a functional role for neutrophil-derived netrin-1 in attenuating myocardial ischemia-reperfusion injury through myeloid adenosine A2b signaling.

論文信息：

論文題目： PMN-derived netrin-1 attenuates cardiac ischemia-reperfusion injury via myeloid ADORA2B signaling

期刊名稱(chēng)：JEM- J Exp Med

時(shí)間期卷：J Exp Med (2021) 218 (6): e20210008.

在線時(shí)間：2021年4月23日

DOI：  //doi.org/10.1084/jem.20210008

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes見(jiàn)刊于JEM：

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體的材料和方法：

JEM期刊缺血再灌注模型外周血單核巨噬細(xì)胞清除解決方案

Monocyte and macrophage depletion