| Background:The four most important pathophysiologies of cerebral ischemia are the release of excitory amino acids,Ca2+overload,ischemia/reperfusion injuries because of the release of reactive oxygen radicals,the inflammatory responses after ischemia. However,these changes are related to gene expression and modulation.Therefore,it’s helpful for us to deeply understand the mechanism of this disease to make researches on gene expression profile.So we studied the gene expression profile of cerebral ischemia in rats.Objective:To explore the dynamic characteristics of gene expression profile after acute cerebral ischemia/reperfusion injuries in rats.Methods:30SD rats were randomly divided into6groups:sham control,1h ischemia group(Timepoint at1hour after ischemia, below were similar),3h ischemia group,6h ischemia group and24h ischemia group. Cerebral ischemic model induced by Using distal middle cerebral artery occlusion (dMCAO). Brain tissuses including pneumbra and ischemic core were dissected at timepoint after ischemia. Gene chip hybridization was used to detect the differently expressed genes. The standards for differently expressed genes was that p-value was lower than0.05and absolute fold change was above2.Results:We controlled the quality of extracted mRNA from the ischemic brain tissues by using Agilent2100Bioanalyzer, and found that partial mRNA dissoluted in ischemia for24hours group,but the rest of mRNAs in other groups are qualified. With time of ischemia extending, differently expressed genes increased gradually. These genes encoding inflammatory factors, chemokines and transcription factors were activated after the start of transcription. Onset of transcription activated by ischemia, the expression of the major histocompatibility complex genes related to adaptive immune response dramatically decreased in the penumbra of ischemia1hour group. We used GO (Gene Ontology) functional annotation to classify genes,and found the classification of the function of differently expressed genes in the ischemic penumbra for1hour and the penumbra of ischemia3h/6h/24h groups were markedly different, and the classification of the function of differently expressed genes in the core of ischemia1hour group and the penumbra of ischemia3h/6h/24h groups were similar. We found a large number of genes were up-regulated in the inflammation related channels, we found in apoptosis pathway, before ischemia for6hours, the expression of apoptosis factors and receptors, apoptosis inhibitory factors raised drammatically, but apoptotic key enzymes Casp family members were rarely expressed. And then the expression of Casp family members increased after ischemia for longer than6hours, when the expression of inhibitor of apoptosis protein was abate and the expression of apoptosis factors and receptors were less than earlier. The genes of MHC in antigen processing and presenting pathway were down-regulated in penumbra of ischemia1h group, but had no differences between ischemia3hours group and the sham control group, parts of genes encoding MHC were up-regulated in penumbra of ischemia6h group, and all genes encoding MHC were up-regulated in penumbra of ischemia24h group.Conclusion:With the time of ischemia extending, there were more differently expressed genes. Time put more impose on the gene expression than space. A number of genes associated with inflammation were dramatically up-regulated. Before cerebral ischemia for6hours, ischemic brain tissues were apt to inhibit apoptosis, and after ischemia for6hours, ischemic brain tissues were apt to proapoptosis. Onset of cerebral ischemia, the innate immune was activated, and then the adaptive immune response was activated. The adaptive immune response was inhibitted at the beginning of cerebral ischemia, and then continued to be activated. Gene expression profile analysis not only provided us with interesting studying points,but also a broad research background, we can understand the pathophysiology of diseases basing on the background of the entire study. |
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