失血性/感染性休克患者易发生急性肺损伤（ALI），发病机制复杂，临床防治效果不佳。II型肺泡上皮细胞(AECII)的细胞学行为是ALI的关键转折点。冷诱导RNA结合蛋白(CIRP)是近年发现的危险信号分子，其表达在急性炎症反应后迅速上调。课题组前期研究发现：1.“二次”打击（失血性休克+感染）小鼠AECII内CIRP显著上调；2.CIRP体外刺激AECII，自噬活性下降、caspase-1激活伴部分细胞焦亡，促炎因子分泌增加。据此我们推测CIRP可能通过抑制自噬、促进焦亡放大炎症反应导致ALI。本课题拟通过体内、外实验及临床样本分析，探讨CIRP作为胞内RNA结合蛋白及胞外DAMP（damage-associated molecular pattern）分子调节AECII自噬和焦亡，参与失血性/感染性休克继发ALI的可能机制，为ALI防治提供新的作用靶点和理论依据。

Hemorrhagic or septic shock is often complicated by acute lung injury (ALI), while the pathogenesis remains obscure and the medical intervention proves challenging. The cytological behavior of type II alveolar epithelial cells (AECII) is the key turning point for ALI. In recent years, it is found that the Cold-inducible RNA-binding protein (CIRP) is up-regulated in these patients, which acts as a pro-inflammatory DAMP molecule. Our preliminary experiments showed that 1. CIRP is significantly up-regulated in hemorrhage-lipopolysaccharides (LPS) “two hits” mice, 2.AECII stimulated by CIRP experienced pyroptosis and weakened autophagy. Previous studies have found that pyroptosis can promote inflammation while autophagy can alleviate inflammation. Therefore we hypothesized that ALI might be related with CIRP 1. as a DAMP molecule to induce pyroptosis accompanied with activation of IL-1β - IL-1RI (IL-1β receptor I) positive feedback pathway ; 2. as a RNA binding protein (RBP) to regulate the transcription and translation of inflammation associated proteins such as hypoxia inducible factor-1 alpha, telosome enzymes, adhesion to inhibit autophagy. In this project we try to explore the participation of CIRP in ALI via regulation of autophagy and pyroptosis. Our research may elucidate the vital roles of CIRP and AECII in the progress of pulmonary inflammation, and provide new therapeutic targets for the prevention and treatment of ALI secondary to hemorrhagic or septic shock.