大鼠激素性股骨头坏死脂代谢基因的作用通路  

Gene expression profiling and pathways related fat metabolisim in rats with glucocorticoid-induced avascular necrosis of the femoral head

作　　者：陈燕平[1] 薛延[2] 黄克勤[3] 张亮[4] 赵建晴[4] 贾丙申[1] 周重光[1] 张万强[1] 郎凤平 

机构地区：[1]中国中医科学院骨伤科研究所,北京100700 [2]北京积水潭医院骨研所,北京100035 [3]北京皇城股骨头坏死专科医院,北京102200 [4]生物芯片北京国家工程研究中心,北京102206

出　　处：《中华骨质疏松和骨矿盐疾病杂志》2010年第3期178-186,共9页Chinese Journal Of Osteoporosis And Bone Mineral Research

基　　金：国家自然科学基金(30472173)资助项目

摘　　要：目的了解脂代谢有关基因表达谱和通路的改变与激素性股骨头坏死发病的关系。方法采用脂多糖(12S 10μg/kg)与甲泼尼龙[20 mg/(kg·d)]连续4 d肌肉注射制作大鼠股骨头坏死动物模型,取模型组(M)和对照组(C)大鼠股骨头进行组织形态计量学分析;测定血清总胆固醇(TC)含量;采用微阵列技术,测定和分析2组大鼠股骨头基因表达。结果 (1)股骨头组织形态学检测显示模型组大鼠发生激素性股骨头坏死,与对照组比较空骨陷窝率明显升高(P<0.05);骨小梁体积、骨矿化速率、毛细血管面积均明显降低(P<0.01)。(2)模型组大鼠血清总胆固醇含量明显高于正常组(P<0.001)。(3)基因表达谱芯片检测结果显示,模型组有111个较对照组差异倍数大于2.0的表达基因。经MAS系统分析后发现有18个显著性变化的通路。(4)模型组大鼠6个与脂肪酸代谢通路(FAM)上调表达的关键基因、2个与脂肪酸在线粒体延长通路的基因(FAEM)、有3个与脂肪细胞分裂素信号通路上调表达的基因(ACK)。结论脂代谢有关基因的表达上调在大鼠激素性股骨头坏死发病机制中起重要作用。Objective To understand the changes of gene expression profiling and pathways related fat metabolism of glucocorticoid-induced avascular necrosis of the femoral head （GANFH） of rats in the contribution to pathogenesis of steroid-induced osteonecrosis. Methods GANFH model rat was given hppolysccharide （ LPS 10μg/kg body wight） and methylprednisolone （ after 24 hours MPSL 20 mg/kg body wight/d for d days） to estabilish a rat model of GANFH. Rats were divided into two groups： control （C） group and model （M） group. Histomorphometric analysis was performed and genes expression was measured and analyzed by genome wide cDNA microarry technology in femoral head of control （C） group and model （M） group. Serum levers of cholesterol （TC） were measured in two groups. Results （ 1 ） Osseous lacuna vacant rate （OLVR） of trabecular bone increased distinctly in model group compared with control group （P 〈0. 05 ）. However volume of trabecular bone （ VTB）, mineral apposition rate （MAR） and capillary surface （CS） significantly decreased in model group compared with control group （P 〈 0. 01 ）. （2） Serum levels of cholesterol significantly increased in model group compared with control group （P 〈0. 001 ）. （3） Total 111 genes expression was changed by a minimum of two-fold and also found that 18 pathways had significant changes in those differential genes by molecule annotation system （MAS） analysis in femoral head of model group compared with normal rats. （4） There were 6 upregulated genes related to fatty acid metabolism （FAM） pathway, 2 upregulated genes related to fatty acid elongation in mito- chondria （FAEM） pathway, 3 upregnlated genes related to adipocytokine signaling pathway （ACK） in femore head of model group compared with control group. Conclusion The data suggest that the upregulated genes related to fat metabolism in their pathways of femoral head of steroid-induced osteonecrotic rats might paly an important role in steroi

关 键 词：激素性股骨头坏死 微阵列技术 通路 脂代谢 基因 

分 类 号：R681[医药卫生—骨科学]