关节纤维化是关节创伤及外固定后常见的严重并发症，目前发病机制未明确。我们的前期研究发现，内质网应激和氧化应激均参与了关节纤维化的发病过程，但两者具体的调控机制仍未清楚。我们进一步的研究表明，关节纤维化过程中内质网应激关键通路PERK/Nrf2信号通路被磷酸化激活，而磷酸化的Nrf2可抑制氧化应激反应。因此，我们提出内质网应激激活PERK/Nrf2信号通路负性调节氧化应激，从而抑制关节纤维化的假说。本研究拟采用免疫共沉淀、蛋白芯片等检测方法，旨在探索在关节纤维化发病过程内质网应激和氧化应激的相互作用机制及PERK/Nrf2信号通路的调控机制，明确Nrf2通过负性调控氧化应激抑制关节纤维化的作用，为确立关节纤维化新治疗靶点带来新的突破。

Joint contracture is a severe complication of post-trauma and external fixation. The pathogenesis of joint contracture is still obscure. Our preliminary experimental results demonstrated that endoplasmic reticulum stress (ERS) and oxidative stress would be involved in the pathogenesis of joint contracture. Furthermore, we figured out that ERS-related PERK/Nrf2 signaling pathway was activated by phosphorylation in joint contracture. Since phosphorylated Nrf2 is the inhibitor of oxidative stress, we infer that ERS-activated PERK/Nrf2 signaling pathway negatively regulates joint contracture by surpressing oxidative stress. Based on our previous study, we will systematically employ the technics including immunoprecipitation and protein array, to analyze the mechanisms of ERS, oxidative stress and PERK/Nrf2 signaling pathway in joint contracture, and to figure out the negative effect of Nrf2 by surpressing oxidative stress. New data from these experiments, not only help to elucidate the mechanisms of joint contracture, but also shed new light on the biological treatment for joint contracture.