α2AR 活化调控肺巨噬细胞极性转换对AKI致ALI的保护作用及机制研究

急性肾损伤（AKI）所致急性肺损伤（ALI）是围术期多器官功能障碍或衰竭常见表现之一，AKI合并ALI时死亡率高达80%，探索相应肺保护手段和机制意义重大。肺内巨噬细胞（MФ）极性失稳态可能是AKI致ALI损伤性炎症反应的关键环节，M1Ф呈促炎活性，M2Ф具抗炎与组织修复功能，以其为靶标的防治研究具重要潜在价值。我们前期基金研究证实，α2肾上腺素受体（α2AR）活化通过肺微血管内皮细胞黏着斑激酶（FAK）信号通路减轻AKI所致肺血管高通透性，同时展现出机制不明的抗炎作用。进一步预实验显示小鼠肺泡MФ的α2AR活化，不仅可调控其极性转向M2Ф，还可逆转LPS所致极性变化从M1Ф到M2Ф。本研究拟通过建立AKI致ALI动物及体外肺血屏障模型，采用实时显微成像及相关分子生物学技术，阐明α2AR活化调控肺MФ保护性极性转换的具体机制及意义，以期为AKI所致ALI的防治提供一种新策略。

Acute lung injury(ALI) induced by Acute kidney injury(AKI) is one of common clinical manifestations of perioperative multiple organ dysfunction or failure. The mortality of combined AKI and ALI is as high as 80%. Therefore, it is of great significance to search for the related methods and mechanisms of lung protection. The imbalance of pulmonary macrophage (MФ) polarity homeostasis may be crucial to the damaged inflammation during ALI induced by AKI. M1Ф possesses pro-inflammatory function while M2Ф exerts anti-inflammatory and tissue repair properties. Macrophage polarity homeostasis-targeted interventions may be an importantly potential value to prevent ALI. The research supported by our previous foundation proved that α2 adrenoceptor(α2AR) activation could attenuate pulmonary vascular hyper-permeability caused by AKI through FAK signaling within pulmonary microvascular endothelial cells . Moreover, α2AR activation provided also the anti-inflammatory effect with an unclear mechanism. Besides, our preliminary experiments demonstrated that in the mice alveolar MФ, α2AR activation orchestrated its polarity from MФ or M1Ф to M2Ф in the presence or absence of LPS. Herein, the aim of the current study is to illustrate the mechanism of pulmonary MФ polarity switch modulated by α2AR activation as well as the value through the in vivo real-time microscopy and molecular biology techniques applied to the animal model with AKI-induced ALI or in vitro pulmonary blood barrier model. The novel strategy for relieving AKI-induced ALI may be anticipated.