周期素依赖激酶抑制剂对大鼠局灶性脑梗死后胶质增生的影响

The effects of cyclin-dependent kinase inhibitor on reactive gliosis of the ipsilateral cortex following MCA occlusion

目的 通过抑制细胞周期素依赖激酶 (cyclin dependentkinase ,CDKs) ,对星形胶。质细胞增殖进行干预 ,以探讨其对胶质增生的影响。方法 建立大鼠大脑中动脉阻塞 (middlecerebralarteryocclusion ,MCAO)再灌流模型 ,随机分为脑缺血对照组和干预组 (分别于再灌流后第 3天、第 5天腹腔注射CDKs抑制剂 ) ,应用免疫印迹和免疫组织化学方法检测各组MCAO后第 4周损伤侧皮层胶质纤维酸性蛋白 (glialfibrillaryacidicprotein ,GFAP)的表达 ;并通过HE染色对皮层中风囊体积进行测定 ,观察CDKs抑制剂对胶质增生的影响。结果 MCAO后第 4周 ,皮层可形成明显的中风囊 ,并且在胶质瘢痕附近存在密集、活化的星形胶质细胞 ;损伤侧皮层GFAP蛋白的表达明显增强。经给予CDKs抑制剂处理后 ,可明显缩小中风囊体积 (P <0 0 5 ) ,并部分抑制了GFAP蛋白的表达 (P <0 0 5 )以及星形胶质细胞的过度增殖。结论 通过对细胞周期蛋白的调控 ,可部分抑制胶质增生 ,从而有可能为神经再生和功能重建提供更有利的生存环境。

Objective Functional significance of reactive gliosis may be beneficial or harmful for neuronal survival and regeneration after central nervous system (CNS) injupy.Cyclin-dependent kinases (CDKs) are commonly known to regulate cell proliferation. The present study aimed to determine whether the addition of CDK inhibitor could reduce astrocyte proliferation as well as limit progressive glial scar.Methods Ischemia/reperfusion injury was induced by temporary middle cerebral artery occlusion (MCAO). Olomoucine (4 mg/kg) was admincstered 3 and 5 days after MCAO. Four weeks post-injury, all rats were killed. Their brains were sectioned and sections were stained with H&E. In the cortex ipsilateral to the side of MCAO, the expression level of glial fibrillary acidic protein (GFAP) was analyzed by Western blot and the localization of GFAP was assessed by immunohistochemistry.Results All brains with temporary MCAO(4 weeks) had cavitation surrounded by glial scar tissue. Astrocytes appeared hypertrophic, with higher density near the glial scarring regions of the ipsilateral cortex.Application of olomoucine could reduce cortical cavitation (P<0.05) and partially inhibitthe astrocyte proliferative response. Western blot analysis from the ipsilateral cortex extractsof olomoucine treated animals also revealed a decrease of GFAP expression after 4 weeks of MCAO compared with control animals (P<0.05).Conclusion These results suggest the hypothesis that, by reducing glial proliferation, CDK inhibitor may help create an environment that is more suitable for neuronal survival and regeneration.