细胞周期调控对局灶性缺血性脑损伤后的保护作用

目的通过抑制细胞周期素依赖激酶(Cyclindependentkinases,CDKS)来对神经元凋亡进行干预,以探讨细胞周期调控与细胞凋亡的关系。方法建立光化学法诱导大鼠局灶性脑缺血模型,并随机分为脑缺血组(对照组和干预组)和假手术组,采用HE染色显示梗死灶,并测定其面积占脑片面积百分率的平均值;通过TUNEL方法检测神经元凋亡;免疫印迹(Westernblot)观察损伤侧皮层周期素蛋白A(CyclinA)和周期素蛋白B1(CyclinB1)的表达。结果缺血后24h对照组梗死灶面积占脑片面积百分率的平均值明显大于干预组(P<0.05),缺血后梗死灶周围可见大量TUNEL阳性染色细胞,且对照组数量明显多于干预组(P<0.05),二者均多于假手术组(P<0.05);缺血后24h干预组大鼠NeuN TUNAL双标阳性表达率明显弱于对照组大鼠(P<0.05);Westernblot显示对照组CyclinA和CyclinB1的表达明显高于干预组(P<0.05)。结论细胞周期抑制剂可部分抑制缺血边缘区神经元的凋亡及减小脑梗死面积,这提示细胞周期调控可能参与了神经细胞的凋亡过程。

Cell cycle regulation provides neuroprotection after focal cerebral ischemia brain damage

Objective The effects of cell cycle modification on neuronal apoptosis were studied by observing neuronal apoptosis after focal cerebral ischemical brain damage (FCIBD) in rats. Methods FCIBD model was induced by photochimistry method. The average area of infarction was calculated by HE staining. The expression of neuronal apoptosis was observed by TUNEL and immunofluorescence technique, protein levels for CyclinA and CyclinB1 was measured by Western blot from the damaged and sham animals finished at 24 h,7 and 3 days. Results The average infarct area of treated rats was smaller than that of control anamals (P< 0.05). Olomoucine significantly reduced the number of apoptotic cells. In parallel studies, Western blot showed incerased protein levels of CyclinA and CyclinB1 after damage in control rats, which was inhibited when Olomoucine was administed. Conclusions Our results suggested that cell cycle inhibitor could partially inhibit neuronal apoptosis as well as decrease area of infarction after FCIBD.