The Effects of Recombinant Adeno-Associated Virus Vector Delivery of Angiotensin Ⅱ Type 1 Receptor shRNA on Blood Pressure and Angiotensin Ⅱ Type 1 Receptor mRNA Expression in Renal Hypertensive Rats / 中华高血压杂志

ABSTRACT

Background Hypertension is a multigenetic inheritable disease.Gene therapy by regulating gene expression showed long term effects and less side effects,and has been emerged to be a potential and prospective treatment.Objective To investigate the effects of retroviraladeno-associated virus vector containing shRNA targeted on the AT1R gene (rAAV-AT1R-shRNA) on blood preesure(BP) in renal hypertensive rats,and the inhibitory effect of RNA interference (RNAi) on AT1R mRNA expression in renal hypertensive rats.Methods Two-kideny one-clip (2K1C) renal hypertension (RH) were established in SD rats and randomly to receive rAAV-AT1R-shRNA,1.5?109 particles/mL(n=12,ip),as treated group or retroviral vector (rAAV-EGFP),2.9?109 particles/mL,ip,as vehicle group,normal SD rats served as controls (n=12).SBP was measured before and after treatment.Animals were euthanized and blood,brain,heart,liver,kidney,aorta and adrenal gland were collected to identify the sites of rAAV-AT1R-shRNA expression by fluorescence microscope.Angiotensin Ⅱwas assessed by radioimmunology.Results 24 hours after single injection of rAAV-AT1R-shRNA,SBP was reduced by (22.3?5.5)mmHg compared to before intervention (P