摘要
目的通过基因芯片寻找大鼠激素性股骨头坏死（steriod—induced necrosis of femoralhead，SINFH）组织中表达变化的氧化应激相关基因，探究氧化应激诱发或加重SINFH的始动因素和分子机制。方法20只成年健康Wistar大鼠随机分为对照组和模型组，每组10只。模型组大鼠腹腔注射大肠杆菌内毒素后，于左侧臀肌注射大剂量甲基泼尼松龙，建立SINFI-I模型；正常对照组大鼠腹腔注射大肠杆菌内毒素后，于左侧臀肌注射相同剂量生理盐水。6周后取两组大鼠的左侧股骨头标本进行组织病理学观察，并抽提各组大鼠股骨头组织的mRNA，经反转录获得大鼠股骨头组织cDNA，进行基因芯片检测。检测结果经荧光定量PCR验证。结果组织病理学观察显示模型组大鼠股骨头出现骨小梁紊乱、变细，骨细胞坏死，空骨陷窝率增加；对照组大鼠未见股骨头坏死。模型组基因芯片检测发现27条氧化应激相关基因存在差异表达，其中COX6A2、COX412、SOD3和DUSPl等4条基因的表达与对照组存在显著差异，且均呈下调表达。这些显著差异表达基因的功能涉及抑制活性氧自由基（ROS）生成，加速ROS清除以及保护组织免受氧化损伤等方面。结论大鼠SINFH组织中氧化应激相关基因的表达存在变化，初步提示COX6A2、COX412、SOD5和DUSPl基因是氧化应激在SINFH发生、发展过程中起作用的关键基因。
Objective To identify significantly differentially expression of rat by genes chip, try to find out the initiating factors and molecular mechanisms that oxidative stress originate or strengthen the steriod-induced necrosis of femoral head （SINFH）. Methods Twenty Wistar rats were dived into experimental group and control group randomly. The rats were injected intraperitoneally whith endotoxin, and then injected intramuscularly with high-dose methylprednisolone or saline in experimental group and control group respectively. The mRNA was extracted from the femoral head of rats inevery group, and the cDNA probes were obtained by inverse transcript, and then carried out microarray detection. The quantitative RT-PCR was used to cotffirrn the results of the microarray. Results Histopathological findings revealed that the experimental group rats had femoral head necrosis, trabecular bone disorders, thinning, bone cell necrosis, and the rate of empty lacunae increased, and in control group no femoral head osteonecrosis was found. Total of 27 differentially expressed genes were found, and of which 4 genes （COX6A2, COX412, SOD3, and DUSP1） were significantly different. The expression of these 4 genes were down-regulated. The functions of these four genes involved in inhibition of reactive oxygen species （ROS） generation, accelerated removal of ROS and protection tissue from oxidative damage and so on. Conclusion The expression of oxidative stress-related genes in SINFH of rats exist change. COX6A2, COX412, SOD3, and DUSP1 are key genes in process of oxidative stress originate or strengthen the SINFH.
出处
《中华骨科杂志》
CAS
CSCD
北大核心
2011年第7期794-799,共6页
Chinese Journal of Orthopaedics
基金
国家自然科学基金资助项目（30672702）
