关键词：关节炎；骨骨折；线粒体；软骨
摘 要：The purpose of this research is to investigate a novel therapeutic approach to preventing PTOA by addressing mitochondrial dysfunction and oxidative damage in cartilage. Thus far we have tested a number of compounds for therapeutic activity in a chondral injury model that involves a high energy impact to the medial femoral condyle of rabbits. The selection of compounds included an oxidant scavenger, (N-Acetylcysteine), a drug that reduces mitochondrial superoxide production by blocking electron flow through complex I (amobarbital), and two drugs that block actin and tubulin remodeling (cytochalasin B and nocodazole respectively). Treatments were administered acutely after injury (N-acetyl cysteine and amobarbital) or prior to injury (cytochalasin B and nocodazole). At seven days post-op the rabbits were euthanized and the injured cartilage was analyzed for viability, and ATP. While NAC at a low dose was effective in preventing injury-related chondrocyte losses, amobarbital, nocodazole, and cytochalasin B were more effective at sparing metabolic activity. With these data in hand we are ready to go forward with the long-term rabbit study, in which we will determine the effects of amobarbital and nocodazole on cartilage degeneration (Aim 2). The most effective treatment will be tested in a porcine intraarticular fracture model (Aim 3).