西比灵对大鼠脑缺血边缘系统细胞凋亡及其调节基因转录的影响

Effect of sibelium on apoptosis and transcription of converting gene in limbic system of rats' cerebral ischemia

目的 研究西比灵对大鼠急性脑缺血边缘系统细胞凋亡及 bcl- 2家族、白介素 - 1β转化酶 (ICE)基因的影响及机制。方法 制作大鼠大脑中动脉阻塞 (MCAO)模型 ,监测生理盐水对照组、西比灵 5 0μg干预组和西比灵 10 0μg干预组的颞皮质、海马和下丘脑的凋亡细胞数、bcl- 2和 ICE基因阳性转录细胞数的动态变化。结果 西比灵 10 0μg干预组各时相的凋亡细胞数极显著低于其它两组 (P<0 .0 0 1)。生理盐水对照组和西比灵 5 0μg干预组各部位于再灌注 2 4小时 bcl- 2基因转录开始下降 ,急剧下降期位于再灌注 2 4～ 48小时。西比灵 10 0μg干预组于再灌注 2 4小时开始下降 ,并于以后各时相继续缓慢下降并始终未达谷底。西比灵5 0μg干预组与生理盐水对照组各时相点无显著差异 (P>0 .0 5 )。西比灵 10 0μg干预组各时相的 bcl- 2基因阳性转录细胞数显著高于其它两组 (P<0 .0 5 )。 ICE基因的同期转录水平几乎与 bcl- 2基因转录水平呈反向变化。结论 脑缺血及再灌注时 bcl- 2基因转录受抑制 ,而 ICE基因转录上调 ,西比灵能显著削弱这些基因转录的变化、减轻细胞凋亡。西比灵的这种作用有剂 -效依赖性。

Objective To study the effect and the mechanism of sibelium on apoptosis and transcription of bcl 2 clan and interleukin 1β converting enzyme(ICE) gene in limbic system after rats' middle cerebral artery occlusion(MCAO).Methods MCAO model was made, and determined the dynamic changes on the cell counts of apoptosis, bcl 2 clan and ICE gene positive transcription in temple ortex, hippocampus and hypothalamus in the controls of normal saline,sibelium 50 μg intervenient group and sibelium 100 μg intervenient group during rats MCAO or reperfusion.Results The apoptosis counts of every times in sibelium 100μg intervenient group was significant lower than another two groups( P <0.01). In the control group of normal saline and sibelium 50μg intervenient group, bcl 2 gene transcription began to decease at reperfusion 24 hours. Sharp falling period located during reperfusion 24 to 48 hours after MCAO.The sibelium 100μg intervenient group began to decrease at reperfusion 24 h,and slowly fell but no reaching to the lowest level all along.There was no remarkable difference at every times between sibelium 50 μg intervenient group and the controls (P>0.05).The bcl 2 gene positive transcription cell counts at every times in sibelium 100μg intervenient group were significant higher than another two gruops( P <0.05). ICE gene transcription level at the same period was almost opposite changes compared with those of bcl 2 gene.Conclusion During cerebral ischemia and reperfusion, bcl 2 gene transcription was restrained, while ICE gene transcription was up regulated. Sibelium could alleviate remarkably the transcription of these gene and apoptosis,which had dose effect dependence.