Effect And Mechanism Of Beraprost Sodium On Brain Injury In Global Cerebral Ischemia Reperfusion Rats

Aim: To study the time course change of PGIS-PGI2-IP signalpathway in rat hippocampus after global cerebral ischemia reperfusioninsult at the different reperfusion time points, and to investigate theprotective effect of beraprost sodium on global cerebral ischemiareperfusion injury in rats.Methods: The rat model of global cerebral ischemia reperfusioninjury was established by bilateral common carotid arteries occlusioncombined with systemic hypotension. The cerebral blood flow wascontinuously monitored by moorVMS-LDF laser Doppler blood flowduring the operation phase. The activities of SOD, contents of PGI2andMDA, and expressions of PGIS and IP were detected at the reperfusiontime points of30min,2h,6h,24h,48h,7d and15d, respectively.Beraprost sodium(50and100ug·kg-1) was intragastrically administered30min before the operation. Spatial learning and memory function of ratswere tested with Morris Water Maze. HE staining was employed tomeasure the morphologic change of hippocampal neurons. The SOD activity and MDA content in rat hippocampus were detected by the methodof xanthinoxidase and TBA，respectively. The alteration of PGI2content inrat hippocampus was measured by enzyme-linked immunosorbent assay.The changes of PGIS and IP mRNA expression in rat hippocampus weredetected by RT-PCR.Results: The cerebral blood flow decreased74.45%of the baselineduring the cerebral ischemia phase. Compared with that in the shamoperation group, the spatial learning and memory function in the ischemiagroup were significantly impaired. Hippocampus neurons in the modelgroup showed obviously disordered cell structure and karyopyknosis. TheSOD activity significantly decreased, whereas the MDA and PGI2contentsignificantly increased. The expression of PGIS and IP mRNA in thehippocampus significantly increased in the ischemia reperfusion rathippocampus. Beraprost sodium significantly improved the spatial learningand memory function of global cerebral ischemia reperfusion rats, andobviously prevented the hippocampus neurons from karyopycnosis and loss.In addition, beraprost sodium significantly blunted the decrease of SODactivity and the increase of MDA content and PGI2level in the rathippocampus with global cerebral ischemia reperfusion injury. Beraprostsodium also caused a significantly down-regulation of PGIS and IP mRNAexpression in global cerebral ischemia reperfusion rat hippocampus.Conclusions: Global cerebral ischemia and reperfusion insult results in the change of PGIS-PGI2-IP signaling pathway. Beraprost sodium has aprotective effect on global cerebral ischemia reperfusion injury. Theremodeling of balance of PGIS-PGI2-IP signal pathway may involve inthe neuroprotective mechanism of beraprost sodium.