关节挛缩是关节炎症、创伤及术后常见的并发症，目前发病机制未明确。我们的前期研究表明，分子伴侣CCT-7和GRP78在关节挛缩组织中高表达，提示内质网应激可能参与关节挛缩的发病；进一步研究发现，关节挛缩组织中XBP-1蛋白高表达，且氧化应激也处于高水平，而IRE1/XBP-1信号通路是内质网应激的关键通路。据此，我们提出IRE1/XBP-1信号通路可能参与关节挛缩的调控。本研究拟采用免疫共沉淀、慢病毒转染等方法，探讨IRE1/XBP-1信号通路对成纤维细胞功能的影响，研究XBP-1乙酰化/去乙酰化表观修饰对成纤维细胞活化程度的调控在挛缩进程中发挥的作用，观察在关节挛缩病程中内质网应激与氧化应激的交互作用形式，明确XBP-1通过表观修饰调控关节挛缩的分子机制，阐明内质网应激在关节挛缩发病中的作用模式，为探索治疗关节挛缩的新靶点提供科学依据。

Joint contracture is a common post-arthritis, trauma and operative complication. The pathogenesis of joint contracture is still obscure. Our preliminary experimental results demonstrated that chaperone CCT-7 and GRP78 from the contractive tissue were increasingly expressed with the relation to the severity of joint contracture, indicating that endoplasmic reticulum stress (ERS) would be involved in the pathogenesis of joint contracture. Furthermore, we figured out that XBP-1 as well as ROS levels were increasingly expressed in joint contractive tissue. Since IRE1/XBP-1 signaling pathway is the crucial pathway in ERS, we infer that IRE1/XBP-1 signaling pathway plays an important role in regulating the joint contracture. Based on our previous study, we will systematically compare the variation of fibrous markers, ERS markers and IRE1/XBP-1 signaling pathway expressions in human joint contractive tissue with technics including immunoprecipitation and plasmid vector transfection. Furthermore, we will discuss the effects of IRE1/XBP-1 signaling pathway on fibroblast function, and the effects of acetylation modification of XBP-1 in joint contracture. The interactions of ERS and ROS will also be analyzed to clarify the mechanisms of regulation in joint contracture by XBP-1, and the effects of ERS in the pathogenesis of joint contracture. 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.