ED 31. Adenoviral gene transfer of antisense cDNA of the human PDE5A1 promoter gene to penis augments erectille function in diabetic rabbits

Objective: To investigate whether the adenoviral-mediated expression of the antisense cDNA of the human PDE5A1 promoter gene can imp rove erectile function in rabbits with diabetes mellitus (DM).

Methods: Twenty-five male rabbits was randomly divided into 5 groups as follows: 4 treatment (n=5 in each group) and normal control (n=5) groups. Alloxan was injected intravenously into the treatment groups to establish diabetic erectile dysfunction in animal models. The pAd/CMV/V5/antisense-PDE5A1, pAd/ CMV/V5-GW2lacZ (β-gal group), vehicle and 0. 9% NaCl were transfected into the corpus cavernosum of the DM rabbits in the 4 treatment groups, respectively. Seven days after transfection, the intracavernosal pressure during pelvic nerve stimulation (NSICP) was compared with that in normal control animals. Adenoviral transfection efficiency ofβ-gal reporter gene was measured by Western blot analysis, and cGMP levels in cavernosal tissue were detected by EL ISA.

Results: Seven days after transfection with pAd /CMV/ V5/antisense-PDE5A1, cGMP level in cavernosal tissue (25.6±2.5) fmol/mg protein was significantly higher than those inβ-gal group [(8.8±0.9) fmol/mg protein], vehicle group [(8.3±1.1) fmol/mg protein], DM control group [(7.4±0.8) fmol/mg protein, P<0.05]. The increase in NSICP of the pAd/CMV/V5/antisense-PDE5A1-transfected rabbits [(66.2±3.6) mmHg] was significantly higher than those ofβ- gal group [(38.2±2.5) mmHg], vehicle group [(35.2±2.2) mmHg], and DM control group [(36.6±2.7) mmHg, P<0. 05]. There was no significant difference between the pAd/ CMV/V5/antisense-PDE5A1 group and normal control group [(65.2±3.2) mmHg, P>0.05]. Adenoviral exp ression of β-gal reporter gene was significantly higher in cavernosal tissue inβ-gal group than in other groups.

Conclusions: These results suggest that in vivo adenoviral gene transfer of antisense cDNA of the human PDE5A1 promoter gene to penis can improve erectile function in DM rabbits. The DE5A1 promoter gene may be a novel target gene for gene therapy of ED.