胶原诱导性关节炎大鼠滑膜基因表达谱特征研究

Study on the Gene Expression Profiles of Synovialis in Rats with Collagen-Inducing Arthritis

目的:运用基因芯片技术研究胶原诱导性关节炎(collagen-inducing arthritis,CIA)大鼠滑膜基因表达谱特征,探讨CIA相关致病基因。方法:选用健康雄性Wistar大鼠40只,随机分为造模组、正常对照组(n=8,简称正常组),造模组采用牛Ⅱ型胶原乳剂于大鼠尾根部注射,建立CIA模型。在造模成功大鼠中随机选取8只作为模型组(n=8)。于造模成功后30天,提取各大鼠滑膜总RNA,运用Illumina基因表达谱芯片分析每个样本基因变化。结果:正常组与模型组大鼠滑膜差异表达基因有271条,其中上调基因131条,下调基因140条。差异表达基因主要涉及细胞凋亡、基质金属蛋白酶、癌基因、热休克蛋白、骨桥蛋白、细胞周期、代谢、信号传导通路、趋化因子、黏附分子等。结论:CIA是一涉及多基因表达异常的自身免疫性疾病,筛选到的差异基因如上调表达基因Map3k11、Mmp8、OPN5、Rgs5、Hsph1、Ccl20、Robo4、Hyal4及下调表达基因Cabp1等,有利于阐释RA分子机制,提供RA防治新靶点。

Objective：To study the gene expression profiles of synovialis in rats with Collagen - Inducing Arthritis （CIA） by microarray and to explore genes associating with CIA. Methods ：40 Healthy Wistar rats were randomly divided into making model group and control group（ n = 8 ）. Rats of making model group were injected 0.5mL BC lI （ type 1I col- legan of bovine, BC 11 ） emulsion in the tail to establish CIA model. 8 succeeded CIA rats were randomly selected as model group（n =8）. Rats were sacrificed after 30 days. Total RNA was extracted from synoviocytes of two groups rats,Illumina oligonucleotide microarray was used to characterize geue expression profiles of each sample. Results ：271 differentially ex- pressed genes were identified in CIA rats,including 131 genes up- regulated and 140 down- regulated. The differential genes were associated with apoptosis, matrix metallopeptidase, oncogene, heat shock protein, opsin, cell cycle, metabolism, chemokines, adhesionmolecules, signal transduction passage, etc. Conclusion ： RA is an immunogenic disorder with many abnormal expression genes. The selected genes such as up- regulating expressions of Map3kll, MmpS, OPN5, Rgs5, Hsphl, Cc120, Robo4, Hyal4 and down -regulating expression of Cabpl are benefit to explain the molecule mechanisms of RA,those can provide new target points of preventing and treating RA.