MOLICULAR BIOLOGICAL ANALYSIS ABOUT REGULATION OF INTRACRANIAL PRESSURE BY CNP AND ITS RECEPTOR

在基因水平上，颅内压（ICP）升高和/或脑积水对大脑的影响很少受到关注。本研究旨在探讨颅内压增高模型下大鼠即时早期基因（IEG、c-fos、c-jun）表达的变化；CNP及其受体调控颅内压的分子生物学分析；实验性脑积水中hsp、bax、bcl-2信使RNA的表达参与脑积水痴呆海马形成的机制。得到以下结果：选取ICP可控大鼠，评估中高ICP（1组，保持脑流量）和高ICP（2组，减少脑流量）时的eggs表达。2组大鼠皮层和齿状回c-fos mRNA表达增强。而第1组的c-fos与对照组无明显差异。第1组和第2组c-jun信号均未升高。更多的结果证实，在脑血流维持的条件下，神经元和非神经元细胞能够在基因水平上很好地将ICP增加的应激联系起来，但如果缺血性损伤是累积的，它可以作为IEG表达的中介。海马体的形成参与了脑积水性痴呆的实验数据。本研究的另一个目的是利用分子生物学方法澄清假设。采用原位杂交技术研究高岭土诱导脑积水大鼠脑下皮层形成过程中热休克蛋白（hsp） bax和bcl-2 mRNA的表达。我们的数据显示，hspand bax mRNA在亚急性期齿状回的表达增强。提示脑积水大鼠齿状回发生一定程度的神经损伤和/或细胞凋亡。hsp和bax在齿状回的选择性表达支持了海马形成可能导致脑积水痴呆的假设。少

Little attention has been given to influence of the intracranial pressure (ICP) elevation and/or hydrocephalus to the brain at the level of the gene. Present study was designed to investigate the follows, 1)Changes of immediate early gene (IEG,c-fos, c-jun) expression using increased intracranial pressure model in rat, 2)molicular biological analysis about regulation of intracranial pressure by CNP and its receptor, 3)Participation of the hippocampal formation in hydrocephalic dementia from expression of hsp, bax, bcl-2 messenger RNA in experimental hydrocephalus. Following results were obtained. Using ICP controllable rats, IEGs expression were evaluated in moderately high ICP (group1, CBF was maintained) and severly high ICP (group2, CBF was reduced). Expression of c-fos mRNA was enhanced in the cortex and dentate gyrus of group 2. However, c-fos in group 1 was not different from that of the control group. There was no increase of the signals of c-jun in either group 1 or 2. These re … More sults confirm that the neurons and non-neuronal cells are well able to torelate the stress of increased ICP at the level of the gene, under the condition that CBF is maintained, but if ischemic insult is cumulative, it acts as mediator of IEG expression.Participation of the hippocampal formation in hydrocephalic dementia has been suggested from experimental data. The other purpose of this study was to clarify hypothesis using a molecular biological method. We investigated the expression of heat shock protein (hsp) bax and bcl-2 mRNA in hypocampal formation using kaolin induced hydrocephalus by in situ hybridization technique. Our data showed that the expression of hspand bax mRNA were enhanced on the dentate gyrus in the subacute stage. These results suggest that some neural damage and/or apoptosis takes place in the dentate gyrus of hydrocephalic rat. The selective expression of hsp and bax in the dentate gyrus supports the hypothesis that the hippocampal formation could contribute to dementia in hydrocephalus. Less