酸敏感离子通道（ASICs）属于DEG/ENaC超家族一员，激活可导致胞外Ca2+内流，参与某些病理反应过程。我们前期实验研究证实在AA大鼠关节软骨细胞上有ASIC1a、ASIC2a、ASIC3三个亚基表达，药物抑制其表达及通道开放对关节软骨损伤有保护作用，这种保护作用与抑制软骨细胞凋亡有关。在此基础上试图（1）通过转染特异性小干涉RNA技术，分别使ASICs亚基表达沉默，分析其参与细胞凋亡的作用及亚基类型。（2）建立全细胞膜片钳记录H+ 激活ASICs电流，Fura-4/AM探针与激光共聚焦显微镜检测细胞Ca2+浓度，分析细胞内Ca2+的超载对细胞早期凋亡的影响。（3）用特异性和／或非特异性阻断剂阻断软骨细胞ASICs，分析ASICs开放程度与细胞钙离子依赖性凋亡相关酶的关系。初步阐明Ca2+通透的ASICs在AA大鼠关节软骨细胞凋亡中的作用机制，为RA的临床治疗提供新的策略。

Acid-sensing ion channels (ASICs) are members of the degenerin/epithelial sodium channel (DEG/ENaC) protein superfamily. Activation or sensitization of Ca2+-permeable ASICs has also been demonstrated to be responsible for acidosis-mediated diseases, including ischaemia, inflammation, epilepsy, cancer. However, it is largely unknown how the sensors adjust to these pH changes in RA. Previous studies have indicated that three ASICs subunits are expressed in articular chondrocytes of rats with adjuvant arthritis. In addition, blockade of ASICs attenuates articular cartilage destruction in rats with adjuvant arthritis, which relate to inhibition of apoptosis in articular chondrocytes. On this basis, the stable ASICs-silenced articular chondrocytes, built with RNA interference technology. We analyse the roles of different subunits in apoptosis processing of articular chondrocytes. Furthermore, ASIC currents are recorded with whole-cell patch-clamp and fast-perfusion techniques and intracellular calcium ([Ca2+]i) in chondrocytes, are recorded by using the laser scanning confocal microscopy. We analyzed the effect of Ca2+ overload on early cell apoptosis, and relationship between ASICs activation level and calcium dependence apoptosis enzymes, after suppression the ASICs with a nonspecific blocker or (and) a specific blocker. In this research proposal, we try to clarify the role of ASICs in the apoptosis of articular chondrocytes of rats with adjuvant arthritis, We therefore hypothesized that inhibiting ASICs would provide protection for the articular cartilage in adjuvant arthritis (AA) rats, and can be used as potent therapeutic targets for the treatment of acid-mediated cartilage degenerative diseases in the near future.