Research on prevention and treatment effect of rAAV-PR39-ADM in cerebral ischemia reperfusion injury in rats / 中国药理学通报

ABSTRACT

Aim To investigate the curative effect of rAAV-PR39-ADM,which co-expressed the gene of an-tibacterial peptide (PR39 ) and adrenomedullin (ADM),in a rat cerebral ischemia/reperfusion (I/R) injury.Methods In vitro,Matrigel angiogenesis as-say was made with human umbilical vein endothelial cells.In vivo,the cerebral 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 in-to 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 I/R group.MRI,neurological deficit score,TTC and HE staining were measured respective-ly 1 ,2,3 and 4 weeks after the injection in order to e-valuate the therapeutic efficacy.Results In vitro, rAAV-PR39-ADM group had significant angiogenic effect compared with sham group and null virus group. In vivo,successful I/R model was verified by the ima-ges of MRI.Compared with sham group,the nerve function defect score and the cerebral infarction size in each time nodes were significantly raised in I/R groups (P<0.01).There was no significant difference in in-farct 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 compared with 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.Conclusion The treat-ment of rAAV-PR39-ADM promotes vascular forma-tion,neuron protection and reduces the infarct size in the model of cerebral ischemia/reperfusion.