| Summary: | 博士 === 國防醫學院 === 生命科學研究所 === 95 === Prostaglandin I2（PGI2, prostacyclin）, a potent vasodilator and inhibitor of platelet aggregation and leukocyte activation, is crucial in vascular disease such as stroke. Although the expression of PGIS is validated in the brain, its expression after ischemia-reperfusion remains to be studied. Studies have shown the protective effects exerted by PGI2 analogues on ischemia induced neuronal damages in vivo. We have also demonstrated that gene transfer of COX-1 or COX-1/PGIS protect brain against ischemic injury, however, the functions of COX-1/PGIS gene transfer or PGI2 in vitro remain unclear.
We reported the increase of temporal expression of PGIS mRNA and protein are delayed and transient after ischemia followed by reperfusion of 24 hrs and 72hrs. PGIS mRNA and protein are spatially expressed on penumbra area, pyriform cortex, hippocampal region and leptomeninges. PGIS protein colocalization can be seen at different regions. First, it is colocalized with PECAM-1 in endothelial cells at leptomeninges and large and small vessels; secondly, it is colocalized with NeuN in neuronal cells at penumbra areas; finally, it is also colocalized with OX-42 in microglia cells at penumbra area and GFAP in astrocytes at hippocampal regions. To evaluate its role against ischemic infarct, we found after virus infection for 72hrs and then followed by ischemia-reperfusion, the infarct volume is decreased and only the prostacyclin in the eicosanoids is markedly increased. However, administrating virus infection of PGIS at the same time as carrying out ischemia-reperfusion will have no effect on the infarct volume. PGI2 and TXB2, a metabolite of TXA2, are markedly increased; and the ratio of PGI2 / TXA2 is decreased from 10 to 4.
In vito study, we also demonstrated following results. ( 1 ) OGD led to a time-dependent increase in LDH and decrease in MTT. ( 2 ) OGD induces increases COX-1 and COX-2 protein level, but has no change on PGIS protein level. ( 3 ) Adenovirus mediated over-expression of COX-1/ PGIS ( COP ) upregulates COX-1 and PGIS expression time and dose dependently. ( 4 ) Gene transfer of COP suppresses the increase of LDH and decrease of MTT induced by H/R. ( 5 ) PGI2 or its analogues, iloprost, pretreatment protects CE cells from H/R injury. ( 6 ) Adenovirus mediated gene transfer of COP down-regulated the expression of H/R induced apoptotic related molecules. ( 7 ) PGI2 or iloprost up-regulated of Bcl-2 and Bcl-xL protein levels. In conclusion, PGI2 protects brain injury through upregulating Bcl-2.
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