急性肺损伤（ALI）迄今尚无安全有效的药物干预手段，肺血管内皮细胞损伤是ALI的关键发病机制，有可能成为药物干预新靶点。课题组前期构建的ICAM-1单抗辛伐他汀纳米载体具有肺血管内皮细胞和肺组织靶向性，并显示一定的ALI抗炎作用。更重要的是，我们发现纳米载体可成功输送DNA至细胞核并表达。基于此，为进一步提高ALI的早期干预能力，本项目拟通过联合用药方式，即构建Ang-1基因与辛伐他汀纳米共传递系统，研究其理化性质及靶向性，并以成功建立的ALI细胞模型和动物模型为基础，研究纳米共传递系统对ALI的细胞药效学与动物药效学，评估其抗炎作用及抗细胞凋亡作用等，最后通过探讨纳米共传递系统ALI作用与PI3K/Akt信号通路等的相关性，明确纳米共传递系统对ALI作用的关键机制。本项目旨在将基因治疗与化学药物治疗相结合，从ALI的发病机制出发，以肺血管内皮细胞为干预靶点，探寻一种ALI靶向治疗新途径。

Acute lung injury (ALI) is a disease without safe and effective therapy drugs till now, the injury of pulmonary vascular endothelial cells is the key pathogenesis of ALI, and may become a new target for drug interventions. The simvastatin nanocarriers modified with anti-ICAM-1 are found targeted to pulmonary vascular endothelial cells and lung tissue, and displayed ALI anti-inflammatory effect in our previous studies. Moreover, we found that the nanocarriers can successfully transport DNA to the nucleus and express of protein. In order to further enhance the ability of early intervention to ALI, we introduced combined drug therapy method to ALI, namely, to preparing Ang-1 gene and simvastatin combined nanocarrier in this study. The purposes are to study the physicochemical properties of the combined nanocarrier and its target ability to ALI induced pulmonary vascular endothelial cell and lung tissue. Furthermore, based on the ALI cell model and animal model successfully developed, the cellular pharmacology and animal pharmacology of the combined nanocarrier will be evaluated by determining its anti-inflammatory effect and anti apoptosis effect to ALI. Lastly, the correlation of the combined nanocarrier between PI3K / Akt signaling pathway and Ang-1 protein expression are evaluated. In all, this study aims to develop a new ALI treatment method, which combined gene therapy and chemotherapy, and from the pathogenesis of ALI, and targeted to pulmonary vascular endothelial cells.