黏液高分泌是PM2.5长期暴露所致气道炎症的重要表现，此高分泌粘蛋白（MUC）的表型主要为MUC5AC。目前PM2.5对气道的致炎效应及上皮损害作用已有较明确认知，但对其导致黏液中高分泌的认识仍停滞于源自炎症因子的继发效应，此只限于转录水平提升的机制无法解释MUC5AC后期加工能力大幅提升的需求。考虑到氧化应激是PM2.5的主要致炎机制，故气道上皮细胞应可藉氧化应激诱导内质网整合应激反应（ISR）提升蛋白加工负荷，该效应系通过影响信号识别颗粒（SRP）和亲水性移位通道复合体Sec61介导雏形肽向内质网移位这两个节点实现的。本研究采用体外培养细胞，观察PM2.5刺激下ISR相关效应蛋白的表达及分布特点，以及SRP和Sec61的变化特征，并观测两组蛋白间的相互作用。并籍缺陷基因转染、RNA干扰等节点抑制的方法，验证此两个门控因子的地位，了解ISR对其介导作用的影响，有望为防治提供有效靶点。

Airway mucus hypersecretion is the major pathologic feature of chronic airway inflammation induced by PM2.5 exposure. It is known that PM2.5 could induce inflammation and airway epithelia injury, Mucin(MUC) 5AC is the secondary effects induced by inflammation, the regulation of mucin secretion, which is known related to the regulation of MUC5AC transcription, can not well explain the substantial increasing of mucus hypersecretion. We speculate that under the stimulation of PM2.5, post-translational MUC5AC protein modifications are altered by oxidative stress-induced endoplasmic reticulum integrated stress response(ISR). This effect is achieved by affecting the signal recognition particle (SRP) and the endoplasmic reticulum (ER) membrane protein translocator Sec61, which interacted to mediate prototype peptide transferring to endoplasmic reticulum. In this research, we will detect the expression and distribution of ISR-related protein in airway epithelial cell cultured in vitro, the alteration of SRP and Sec61 protein and their interaction will be observed by co-immunoprecipitation. Then we will verify the effects of SRP and Sec61 on MUC5AC protein secretion by negative-gene transfection, postive-gene transfection, and RNA interference, also the effect of ISR on the interaction of SRP and Sec61 will be elucidated. This study will improve our understanding of the mechanism involved in mucus hypersecretion under PM2.5 exposure, also it may provide some effective targets for the prevention and intervention of mucus secretion.