假体松动是关节置换术后最主要的并发症，尚缺乏有效防治。已证实假体磨损颗粒刺激巨噬细胞导致慢性炎症，ROS过量产生可加重炎症反应，均与假体松动密切相关。申请者前期发现,松动假体的界膜中促进ROS生成的酶类表达增高，导致ROS产生过量从而加重假体松动。最新研究表明，ECSIT泛素化是mtROS产生的重要途径，可导致ROS总量增加并促进炎症反应。申请者预实验表明：磨损颗粒可上调ECSIT的表达及mtROS的产生。由此假设，ECSIT介导了磨损颗粒诱发的炎症反应并参与假体松动的发生。本研究拟利用免疫荧光技术检测假体界膜中ECSIT的表达情况；同时，通过建立shRNA巨噬细胞模型，观察ECSIT基因沉默对mtROS水平、MAPK与NF-κB通路活性的影响；并进一步探究ECSIT基因缺陷小鼠的假体松动情况，综合分析ECSIT调控mtROS在假体松动中的作用，为防治假体松动提供新靶点。

Prosthesis loosening is the main complication of joint arthroplasty. Its pathogenesis and mechanism have not been identified. Recently, prosthetic wear particles has been shown to stimulate macrophages leading to chronic inflammation. In addition , excessive production of ROS can intensify the inflammatory response.These are closely related to prosthesis loosening. Our previous study has indicated that enzymes promoting the generation of ROS are highly expressed in membrane tissues at the interface of aseptic loosening , which may results in the overproduction of ROS and aggravates prosthesis loosening. Lastest research shows that the ubiquitination of ECSIT is an important way of mitochondrial ROS (mtROS) produced , which results in an increase of the total amount of ROS and promotes inflammation.Our further experiment shows that wear particles can increase the expression of ECSIT and production of mtROS. We hepothesize that ECSIT can enhance the inflammatory response induced by wear particles and participate in the occorrence of prosthesis loosening. Based on our previous study and latest researches, we planned to: (1) collect tissues of interface membranes around implants to analyze ECSIT expression by immunofluorescence method; (2)shRNA macrophage model is constructed to test whether MAPK pathway or NF-κB pathway is involved in the regulation of mtROS by ECSIT; (3) animal model of ECSIT-/- mice is required to explore the effection of ECSIT gene defect on the prosthesis loosening situation . After the researches above, we hope to find out the correlation between ECSIT and mtROS in local periprosthetic inflammation and verify the mechanism of regulation of ECSIT on mtROS in the development of loosening .Therefore it may provide a scientific basis for ECSIT and mtROS as a target for prevention and cure of loosening.