Research On The Effect Of RAAV Co-expressed Angiogenic Peptide (PR39) And Vasodilator Peptide (ADM) In The Cerebral Ischemia Reperfusion Injury In Rats

AimTo investigate the curative effect of rAAV-PR39-ADM,which co-expressed the gene of antibacterial peptide(PR39)and adrenomedullin(ADM),on a rat cerebral ischemia reperfusion injury model.MethodsIn vitro: cell proliferation assay and matrigel angiogenesis assay were performed on human umbilical vein endothelial cells.In vivo: The cerebral ischemia reperfusion(Ischemia/ reperfusion,I/R)model was established by the occlusion of the cerebral artery for 2h and then reperfused for 24 h.SD rats were randomly divided into Sham group,I/R+ normal saline group,I/R+ null virus(AAV)group,and IR + rAAV-PR39-ADM group.rAAV-PR39-ADM,saline and null virus were administered through the femoral vein after 24 h of the reperfusion in the I/R groups.MR,neurological deficit score,TTC and HE staining were measured respectively at 1,2,3and 4weeks after the injection in order to evaluate the therapeutic efficacy.ResultsIn vitro: rAAV-PR39-ADM group has significant proliferative and angiogenic effect compared with sham group and null virus group.In vivo: I/R model was successful which verified by the images of MR.Compared with the Sham group,the nerve function defect score and the cerebral infarction size in each time nodes were significantly raised in the I/R groups(P<0.01).There was no significant difference in infarct size and nerve function defect score between I/R+ normal saline group and I/R+ null virus(AAV)group,and obviously,the IR + rAAV-PR39-ADM group lowered these indexes versus the other two groups.HE staining showed that the number of neurons,new capillaries vessels of I/R+PR39-ADM group were significantly more than those in group I/R and group I/R+ null virus.ConclusionThe treatment of rAAV-PR39-ADM promotes vascular formation,endothelial cells proliferation,neuron protection,blood supply and reduces the infarct size in the rat model of cerebral ischemia / reperfusion.