CDK抑制剂olomoucine对星形胶质细胞增殖活化的影响

目的 观察体外培养的星形胶质细胞(astrocyte，AS)对物理损伤的反应，探讨细胞周期调控对AS活化及增殖的影响。方法 建立体外培养大鼠纯化的AS机械损伤模型，利用免疫细胞化学方法观察损伤区的细胞增殖细胞核抗原(PCNA)、5-溴脱氧尿苷(BrdU)的动态变化；以及周期素依赖的蛋白激酶(CDK)选择性抑制剂olomoucine干预后PCNA、BrdU表达的变化。结果 物理损伤后24h，损伤边缘区AS明显活化，细胞数目增加、胞体肥大，且交织成网状；PCNA表达增强，BrdU阳性细胞比率增加，大量AS进入增殖期。特异性细胞周期抑制剂olomoucine干预后，AS的PCNA表达增强被抑制，胞体肥大程度减轻，BrdU阳性细胞比率减少。结论 损伤刺激可促使胶质细胞细胞周期(cell cycle)启动、反心性增殖活化：olomoucine可以通过抑制CDK调控反应性AS的肥大、增殖。

Effect of Olomoucine on Proliferation and Activation of Astrocytes

Objective To observe the responses of in vitro cultured astrocytes (AS) to mechanical injury,and the effect of cell cycle regulation on the activation and proliferation of AS.Methods The model of mechanical injury on in vitro cultured and purified AS was made. The dynamic changes of proliferating cell nuclear antigen (PCNA),5-bromodeoxyuridine (BrdU) in the AS in the injured region were observed by using immunochemistrical method in the presence or absence of olomoucine.Results 24 h after injury,AS in the injured region had hypertrophy,proliferation,and the expression of PCNA and the percent of the BrdU-positive cells were increased. After treated with olomoucine,the hypertrophy of AS was attenuated and the expression of PCNA and the percent of the BrdU-positive cells were decreased.Conclusion Mechanical injury can promote the initiation of AS cell cycle and activation of responsive proliferation. Olomoucine could modulate the hypertrophy and proliferation of AS effectively by regulating cyclin-dependent protein kinase.