选择性CDK抑制剂对大鼠局灶性脑缺血后胶质增殖及疤痕形成的抑制作用

目的:探讨选择性周期素依赖性蛋白激酶抑制剂Olomoucine对局灶性脑缺血后星形胶质细胞增殖及胶质疤痕形成的抑制作用。方法:将72只SD大鼠随机分为假手术组12只、模型组27只和干预组33只。3组均手术暴露颅骨,模型组和干预组建立光化学法诱导大鼠局灶性脑缺血模型,之后干预组腹腔注射Olomoucine,分别将3组大鼠于处理后3、7、30 d处死,应用免疫组织化学法检测梗死灶周围胶质纤维酸性蛋白(GFAP)的表达;Western blot法观察损伤侧皮质GFAP、增殖细胞核抗原(PCNA)、周期素蛋白A(CyclinA)和周期素蛋白B1(Cy-clinB1)的表达。结果:缺血后各组梗死灶边缘区GFAP表达明显增强,缺血后7和30 d模型组GFAP表达明显强于干预组(P<0.05),并且7和30 d对照组缺血边缘区可见胶质疤痕形成,尤以30 d最为明显;GFAP、PCNA、Cy-clinA和CyclinB蛋白的表达,模型组明显高于干预组(P<0.05)。结论:Olomoucine可部分抑制胶质细胞的活化增殖及疤痕的形成。该结果提示调控细胞周期可能是治疗脑缺血新的方向。

Effect of Olomoucine on Astrocyte Proliferation and Scar Formation after Focal Cerebral Ischemia

Objective: The effect of a cell cycle inhibitor,olomoucine,on astrocytic proliferation was studied by measuring astrocytic proliferation and scar formation after focal cerebral ischemia in rats.Methods: An ischemic rat model was generated by photochemistry method.The expression of glial fibrillary acidic protein(GFAP) was studied by immunofluorescence.Protein levels for GFAP,proliferation cell nuclear antigen(PCNA),cyclin A and cyclin B1 were investigated by Western blot at days 3,7 and 30 after operation. Results: Olomoucine significantly reduced the expression of GFAP.In parallel study,glial scar tissue was observed near infarct regions in control rats at 7 and 30 days,and its density of scar formation was significantly greater at 30 days than at 7 days.Olomoucine significantly inhibited scar formation.Western blot showed increased protein levels for GFAP,PCNA,CyclinA and CyclinB1 in control rats,while the up-regulation of the proteins above was inhibited by olomoucine.Conclusion: The study suggested that olomoucine could significantly inhibit activation,proliferation and scar formation of astrocytes.Regulating cell cycles may provide a new method for treating cerebral ischemia.