经上轮面上基金资助，我们发现：1）我们在研治疗ALI新药(HA1600)能明显增加肺SOCS1表达。细胞转染SOCS1表达质粒后，毒烟诱导的细胞凋亡和炎症反应减少；2）毒烟诱导的肺损伤在MiR155敲除鼠明显减少。HA1600能明显抑制毒烟诱导的肺MiR155表达；3）毒烟使MiR155敲除鼠肺SOCS1增加。我们推测：HA1600通过抑制MiR155促进SOCS1, 从而抑制毒烟诱导肺损伤。我们提出五个目标去检验我们的推测:1）确定HA1600通过SOCS1抑制毒烟诱导的肺DISC形成以及炎性小体组装；2）确定MiR155靶向作用SOCS1参与毒烟诱导的肺损伤；3）确定MiR155经DISC形成参与毒烟诱导的上皮细胞凋亡；4）确定MiR155参与毒烟诱导的炎性体形成；5）确定HA1600通过抑制MiR155促进SOCS1，进而抑制毒烟诱导的肺DISC形成以及炎性小体组装。

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are among the most devastating causes of fatality in critically ill patients. Smoke-induced severe ALI/ARDS is often fatal. During the last cycle of our grant, we discovered that: 1) HA1600, a new ALI drug candidate, can significantly increase lung SOCS1 expression. Smoke-induced apoptosis and inflammatory responses were reduced in the cells transfected with SOCS-1 expression plasmids.2) MiR-155 deficiency protects against smoke-induced lung injury. HA1600 can significantly decrease smoke-induced lung MiR-155 expression. 3) Smoke induces increased lung SOCS-1 expression in MiR-155-/- mice. 5) We hypothesize that HA1600 decreases smoke-induced apoptosis and inflammation via SOCS-1 by inhibiting MiR-155. We propose the following specific aims to investigate our hypothesis: 1) To elucidate that HA1600 suppresses DISC formation and inflammasome assembly in smoke-induced lung injury via SOCS-1; 2) To elucidate whether MiR-155 targets the SOCS-1 in smog-induced lung injury; 3) To determine that MiR-155 is involved in smoke-induced epithelial apoptosis through DISC formation; 4) To determine that MiR-155 is involved in smoke-induced inflammasome assembly; 5) To determine that HA1600 inhibits DISC formation and inflammasome assembly via SOCS1 by inhibiting MiR-155 in smoke-induced lung injury.