Abstract:

Objective To explore the therapeutic effect of transfecting the vascular endothelial growth factor (Vegf) gene in vivo on the mice with pulmonary hypertension induced by chronic hypoxia. Methods Thirty six male mice were randomly divided into 3 groups: P-V group, PAH group and control group, 12 mice per group. The mouse model was prepared using normal pressure intermittent hypoxia method. After four weeks, the mice in P-V group were transfected with pBudCE4.1-VegfEGFP by PEI-mediated in vivo, and the mice in other groups were treated with saline.Hypoxia was continued while transfection. The mean pulmonary artery pressure(mPAP), arterial gas analysis, right ventricular hypertrophy index［RV/(LV+S)］ as well as pulmonary microvascular changes were observed after 30 days. The RT-PCR, Real-time PCR, ELISA, and nitrate reductase method were used in order to detect expression of EGFP, amount of Vegf mRNA, the level of VEGF and NO for pulmonary tissues, respectively. Results Compared with the control group, mPAP, right ventricular hypertrophy and wall thinckness (WT) increased in the PAH group (P<0.05). The extent of mPAP increasing,right ventricular hypertrophy and pulmonary artery WT had reduced in P-V group compared with the PAH group(P<0.05). Vegf mRNA,VEGF and NO protein expressions increased in lung tissue of the P-V group compared with the PAH group(P<0.05). Conclusion After transfecting the exogenous Vegf gene into mice, Vegf mRNA and protein expressions increased in the lung tissue of the mice, reduced the thickening of the small arteries and decreased the right ventricular hypertrophy index, and mPAP in mice of pulmonary hypertension induced by chronic hypoxia.

Key words: Vascular endothelial growth factor, Pulmonary arterial hypertension, Transfection, Gene therapy, Real-time PCR, Mouse