MiR-199a Expression In Rats With Cerebral Ischemic Tolerance Process

Purpose:Ischemic tolerance is a condition of increase resistance to ischemic injury as a result of the activation of endogenous adaptive mechanisms by preconditioning. Hypoxia inducible factor (Hif)-1a is an important transcription factor during ischemic tolerance. It accounts for the transcription of most of genes during ischemic tolerance. miRNAs are a kind of21-23nt small RNAs that specifically target mRNA and inhibit translation or induce its degradation. It is reported that miR-199a is downregulated by hypoxia, which is required for the upregulation of its target, HIF-1a. In our study, we induce cerebral ischemic tolerance by peritoneal injecting3-NPA to rats, and study the expression and function of miR-199a during cerebral ischemia.Method:i. Construction of rat cerebral ischemic tolerance model:The rats were administrated3-NPA or vehicle (saline)3days before permanent occlusion of the middle cerebral artery. The infarction volumes were measured the next day after operation and submitted to2-tailed t-test. Ii. Measurement of the expression of miR-199a and HIF-1a during rat cerebral ischemic tolerance:The rats fall in4groups randomly, and receive vehicle,3-NPA, vehicle+MCAO or3-NPA+MCAO respectively. All the rats were killed on the forth day, cerebral cortexes were take and submitted to real-time PCR for miR-199a and HIF-1a mRNA. The results were submitted to2-tailed t-tests.Result:i. The infarction volume of rats of3-NPA group (245.43+25.24mm3) is21.76%reduced compared to those of control group (313.67±26.29mm3), the difference is statistical significant, ii. The relative expression of miR-199a of3-NPA group (1.20±0.55) decreased64.3%compared to those of control group (3.39±0.78), the difference is statistical significant. The relative expressions of other groups have no significant difference. The expression of HIF-1a of all groups have no significant difference.Conclusion:During cerebral ischemia, the expression of miR-199a in rats cerebral cortex is significantly reduced, the relationship between the expressions of miR-199a and HIF-1a remain for further studies.