Flavopiridol对大鼠局灶性脑缺血后神经元cyclin D_1蛋白表达的影响  

Effects of Flavopiridol on the expression of cyclin D_1 in focal cerebral ischemia in rats

作　　者：张家堂[1] 郎森阳[1] 匡培根[1] 张风英[1] 刘洁晓[1] 王俊华[2] 

机构地区：[1]解放军总医院神经内科,北京100853 [2]解放军总医院微循环室,北京100853

出　　处：《中风与神经疾病杂志》2001年第6期332-334,共3页Journal of Apoplexy and Nervous Diseases

摘　　要：目的 观察大鼠局灶性脑缺血后神经元内细胞周期蛋白 Ｄ １（ｃｙｃｌｉｎ Ｄ１）的蛋白表达与神经细胞凋亡的关系以及Ｆｌａｖｏｐｉｒｉｄｏｌ对其的影响。方法 采用线栓法大鼠大脑中动脉持续栓塞模型，应用免疫组化和ＴＵＮＥＬ染色方法观察缺血组、Ｆｌａｖｏｐｉｒｉｄｏｌ治疗组（分高剂量ＦＨ组和低剂量ＦＬ组）和假手术组神经元阳性细胞染色数量及分布情况。结果 ｃｙｃｌｉｎ Ｄ１蛋白和凋亡细胞分别自缺血后 ６ｈ和１２ｈ开始表达，前者缺血后４８ｈ达高峰；后者缺血后７２ｈ 达高峰，ＦＨ组和ＦＬ组各相应时间点ｃｙｃｌｉｎ Ｄ１蛋白表达均明显减少（Ｐ＜０．０１）；ＦＬ组各相应时间点凋亡细胞明显减少（Ｐ＜０．０１）；ＦＨ组仅在缺血４８ｈ凋亡细胞明显减少。相邻切片可见ｃｙｃｌｉｎ Ｄ１蛋白表达和凋亡细胞染色区域基本相同。结论 ｃ ｙｃｌｉｎ Ｄ１的蛋白表达可能诱发缺血神经细胞的凋亡，Ｆｌａｖｏｐｉｒｉｄｏｌ通过抑制ｃｙｃｌｉｎ Ｄ１的表达而减少缺血后神经细胞的损害，但同时Ｆｌａｖｏｐｉｒｉｄｏｌ本身也可能引起神经细胞凋亡。Objective To investigate the effects of Flavopiridol on expression of eyclin D1 protein and neu- ronal apoptosis in permanent focal cerebral ischemia in rats. Methods A model of middle cerebral artery occlu- sion (MCAO) in rats was performed with intraluminal filament occlusion. The rats of Flavopiridol group (Flavopiridol concentration: 1mmol/L. FH group: 200μl/kg; FL group: 100μl/kg) were treated 30 minutes before and 2d, 3d after the operation. The immunohistochemistry and TUNEL staining was respectively used to observe the distribution and quantities of cyclin D1 protein and neuronal apoptosis in the brain tissues following the shamed operation and permanent MCAO for 3h, 6h, 12h, 24h, 48h, 72h and 7d respectively. Results A significant in- crease in cyclin D1 immunostaining and TUNEL positive staining began to be detected at 6h and 12h after MCAO in the neurons of the ischemia penumbra respectively. The immunoreactivity of cyclin D1 was most marked at 48h, as the TUNEL staining was at 72h. The difference of immunoreactivity of cvclin D1 among ischemic group and FH or FL group was significant (P <0. 01). The difference of TUNEL staining among ischemic group and FL group was also significant (P <0.01). But FH group decreased TUNEL staining remarkably only at 48h after MCAO (P < 0.01). Conclusion The induction of cyclin D1 protein at the ischemia penumbra indicated they might involve in the mechanism of neuronal apoptosis. Flavopiridol reduced the neuronal apoptosis through down-regulating cyclin D1 expression. But Flavopiridol itself might induce neuronal apoptosis.

关 键 词：脑缺血 细胞周期蛋白D1 FLAVOPIRIDOL 蛋白表达 神经元 细胞凋亡 

分 类 号：R743.31[医药卫生—神经病学与精神病学]