The Studies Of RAAV9Vector-Targeted HIF-1αGene Therapy For Myocardial Ischemia In Vivo

Objective:Wistar rat myocardial ischemia model by coronary artery ligation was constructed.To evaluate the effect of Hypoxia Inducible Factor-1α(HIF-la) gene to acute myocardial infarction of rat through tail vein injection of rAAV9-MHC-TnT-HIF1α.Methods:Wistar rat ischemic heart animal model was constructed by left anterior descending coronary artery ligation.36ligated animals were divided into3groups(12each).1day later,2groups were injected at the tail vein with rAAV9-MHC-TnT-HIF1α(Gene group), rAAV9-MHC-TnT-LacZ(Control group).The left one(Model-assessment group) was served as model assessing.Another12rats without ligated were used as a sham operation group.4weeks after the injection, the rat cardiac function was measured by TM_WAVE system.CD31factor were identified by immunohistochemical stain;size of infarcted area was calculated by Evan’s blue stain.HIF-1α gene expression was evaluated by RT-PCR.Results:83.7%(36/43) of the ischemic models, constructed by coronary artery ligation, were qualified for the next study.2weeks after the ligation, the animals had smaller infarcted area (P<0.05) and better heart performance than those of4weeks.4weeks after the transplantation, the gene group animals’infareted heart size was smaller than that of control group’s(P<0.05); the heart function, measured by TM_WAVE system, was better than that of control group; the capillary density was more than control group. The expression of HIF-la in gene group was higher than that of control group.Conclusion:Tail vein injection of rAAV9-MHC-TnT-HIF1can iNerease HIF-la gene expression. It also can decrease the infarct size of AMI rats and inerease capillary density signifIcantly.it has obvious protection to AMI in rats.