The Effects Of Inosine On Expressionof Cyclin D1 And CDK4 In Brain After Cerebral Ischemia Reperfusion In Rats

Objective To investigate the relationship between the expression of Cyclin Dl and CDK4mRNA and neuronal apoptosis or gliosis after focal cerebral ischemic reperfusion in rats and to explore the intervention of Inosine.Methods The model of the focal ischemic reperfusion in SD rats was induced by intraluminalmiddle cerebral artery occlusion (MCAO) with a nylon monofilament suture. The Inosine group of rats was treated with Inosine (100mg/kg) intraperitoneally twice before and 12 hours after reperfusion. In situ hybridization was performed to examine the expression of Cyclin D1 and CDK4 mRNA at 2h, 6h, 12h and 1d, 2d, 3d, 7d, 14d of reperfusion and in shame controls. At the same time, the neuronal apoptosis was also detected by TUNEL staining.Results (1)TUNEL-positive neurons appeared from reperfusion 2h and peaked at 1d and 2d incortex and striatum respectively. The difference of TUNEL staining between controlled group and Inosine group was also significant (p<0.05) at 12h, 1d, 2d, 3d, 7d after reperfusion. (2) Cyclin Dl mRNA expression was detected in cortex and striatum of ischemic hemisphere as early as 2h after reperfusion and reached a peak at 12h and 1d in cortex and striatum respectively. (3) CDK4 mRNA was detected at 6h after reperfusion. The expressions of Cyclin Dl mRNA and CDK4 mRNA in the fields were same as apoptosis almostly. The difference of Cyclin Dl and CDK4 mRNA expression between controlled group and Inosine group was significant ( p<0.05 ) at 12h , 1d , 2d , 3d , 7d after reperfusion. (4) Cyclin Dl mRNA expression began to increase significantly in gliosis at 14d after reperfusion between controlled group and Inosine group was significant (p<0.05).Conclusions The induction of Cyclin Dl and CDK4 mRNA expression early at the ischemiapenumbra indicated that they might involve in the mechanism of neuronal apoptosis . Inosine might reduce the neuronal apoptosis through down-regulating expression of Cyclin Dl mRNA and might be involved in the glosis through upregulating expression of Cyclin Dl mRNA.3...