中文摘要：

背景：既往研究表明抵抗素可刺激软骨细胞产生大量趋化因子,在炎症性关节病变中具重要作用,但具体作用机制未明。目的：进一步探讨抵抗素刺激软骨细胞趋化因子CCL3及CCL4基因表达上调的机制。方法：培养人源性软骨细胞,T/C-28a2细胞及ATDC5细胞,采用q PCR检测抵抗素刺激趋化因子基因的作用,C/EBPβ表达,核因子κB亚型及软骨特异性mi RNAs。给予核因子κB抑制剂（IKK-NBD）和C/EBPβ抑制剂（SB303580）,对C/EBPβ及核因子κB的共同调节作用进行检测。在给予抵抗素刺激或无抵抗素刺激时分别进行亚细胞结构定位检测。结果与结论：①抵抗素可非依赖性上调趋化因子基因表达。②软骨细胞对抵抗素刺激应答具有非严格细胞特异性,通过C/EBPβ抑制剂、核因子κB及一些软骨细胞特异性miRNAs,可对趋化因子基因表达进行联合调控。③一过性核因子κB活性增高可增强C/EBPβ活性,且两个转录因子对趋化因子基因CCL3及CCL4的作用均为非依赖性。

英文摘要：

BACKGROUND： Previous studies have indicated that resistin stimulates a large set of chemokines in chondrocytes that are known to be important in inflammatory joint lesions. OBJECTIVE： To further investigate the mechanism of co-regulation roles of transcription and post-transcription in the up-regulation of two chemokine genes CCL3 and CCL4 in chondrocytes in response to resistin. METHODS： Human chondrocytes, T/C-28a2 and ATDC5 cells were cultured. The function of resistin on the chemokine genes, and the expression of C/EBPβ, nuclear factor-κB isoforms and chondrogenic specific mi RNAs were tested by q PCR. The co-regulation of C/EBPβ and nuclear factor-κB was investigated by nuclear factor-κB inhibitor（IKK-NBD） and C/EBPβ inhibitor（SB303580） treatments, and subcellular localization was detected with or without resistin stimulation. RESULTS AND CONCLUSION： Resistin could increase the expression of chemokine genes independently. Chondrocytes reacted in a non-restrictedly cell-specific manner to resistin; C/EBPβ inhibitor, nuclear factor-κB and some chondrogenic specific mi RNAs in a combinatorial manner regulated chemokine gene expression. Theactivity of C/EBPβ was augmented by a transient increase in activity of nuclear factor-κB, and both transcription factors acted independently on the chemokine genes, CCL3 and CCL4.