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目的观察重组人内抑素(rhEndostatin)对佐剂性关节炎(AA)大鼠滑膜组织p21,细胞周期素D1(cyclin D1)及细胞周期素依赖性激酶4(CDK4)基因表达的影响,探讨rhEndostatin抑制AA大鼠成纤维样滑膜细胞(FLS)增殖的分子机制。方法雄性SD大鼠36只,随机分为正常组(n=12)、AA模型组(n=12)和rhEndostatin(2.5mg/kg)治疗组(n=12)。制备AA大鼠模型,分别采用实时荧光定量PCR和Western blotting方法,定量分析rhEndostatin对AA大鼠滑膜组织p21、cyclin D1、CDK4 mRNA及cyclin D1蛋白表达的影响。结果rhEndostatin治疗组大鼠滑膜组织p21、cyclin D1 mRNA和cyclin D1蛋白表达水平降低,CDK4 mRNA表达水平增加,与AA模型组比较,差异均有统计学意义(P<0.01)。结论rhEndostatin降低AA大鼠滑膜组织cyclin D1表达水平可能是其抑制AA FLS增殖的分子机制之一。
Objective To observe the effects of rhEndostatin on gene expression of p21, cyclin D1 and CDK4 in synovial tissue of rats with adjuvant arthritis (AA) To investigate the molecular mechanism of rhEndostatin inhibiting proliferation of AA rat fibroblast-like synoviocytes (FLS). Methods Thirty - six male SD rats were randomly divided into normal group (n = 12), AA model group (n = 12) and rhEndostatin (2.5 mg / kg) treatment group (n = 12). The AA rat model was established. The effects of rhEndostatin on the expression of p21, cyclin D1, CDK4 mRNA and cyclin D1 in synovial tissue of AA rats were quantitatively analyzed by real-time fluorescence quantitative PCR and Western blotting respectively. Results The expressions of p21, cyclin D1 mRNA and cyclin D1 protein in synovial tissue of rhEndostatin-treated group were significantly increased, while the levels of CDK4 mRNA were increased in the rhEndostatin-treated group. The differences were statistically significant (P <0.01). Conclusion rhEndostatin may reduce the expression of cyclin D1 in synovial tissue of AA rats, which may be one of the molecular mechanisms by which rhEndostatin inhibits the proliferation of AA FLS.