肺微血管内皮细胞(PMVECs)受损是脓毒症急性肺损伤(ALI)发病的核心环节。内源性非受体型Tec蛋白酪氨酸激酶参与TLR受体的信号转导，是调节机体免疫功能的重要信号分子。我们预实验发现脓毒症肺组织中Tec激酶呈高表达，体外LPS刺激PMVECs后Tec激酶活化，且细胞通透系数明显增加。因此，我们推测Tec激酶可能增强脓毒症TLR受体途径的信号转导，活化炎性信号通路，引起PMVECs的损伤，参与脓毒症ALI的发生发展。本项目采用脓毒症ALI小鼠模型，并以PMVECs为主要研究对象，应用基因敲除、RNA干扰等技术，观察Tec激酶活化与脓毒症PMVECs通透性增加、细胞因子产生及凋亡的相关性，并明确与其互相作用的TLR4下游信号分子，深入探讨Tec激酶介导脓毒症PMVECs损伤的分子机制。本项目的实施将有助于阐明脓毒症PMVECs损伤的发生机理，并为预防和治疗脓毒症ALI提供新的思路和靶点。

Pulmonary microvascular endothelial cells (PMVECs) play a key role in sepsis-induced acute lung injury (ALI). Endogenous Tec tyrosine kinase, involving in TLR signaling pathway, is an important immunoregulatory molecular. Our preliminary experiments showed that Tec kinase was activated not only in lung tissue of sepsis model, but also in PMVECs stimulated by LPS, which correlated with the increased cell permeability coefficient. Therefore, we hypothesize that Tec kinase can activate TLR-mediated proinflammatory signaling pathways, resulting in PMVECs injury, and involves in the development and progress of ALI induced by sepsis. In this study, a mouse model of CLP-induced ALI is utilized. The main object of the present study is PMVECs and gene knockout and RNA interference techniques are also used. We aim to study the correlation of Tec kinase activation to the increased cell permeability coefficient, cytokine production and cell apoptosis, and to investigate the relation of Tec kinase to the downstreams of TLR4 as well. Based on the above experiments, the molecular mechanism of Tec kinase in sepsis-induced PMVECs injury will be deeply studied. The results of this study will clarify the mechanisms of sepsis-induced PMVECs injury, and provide new ideas and targets in the prevention and management of ALI following sepsis.