Background
Inflammation, fibrosis and autophagy represent closely related factors associated with the pathogenesis of diabetes mellitus erectile dysfunction (DMED). In this study, the therapeutic effect of nitro-oleic acid (NO2-OA) in a streptozotocin-induced rat model of DMED was evaluated.
Conclusions
NO2-OA enhances erectile function within a rat model of DMED by inhibiting inflammation and fibrosis along with activating autophagy.
Methods
Sixty rats were randomly divided into four groups: control, DMED, DMED + Vehicle and DMED + NO2-OA. DMED was induced by intraperitoneal injection of streptozotocin in male rats. Blood glucose and body weight were measured every 2 weeks. After 4 weeks of NO2-OA treatment, erectile function was measured by electrical stimulation of cavernous nerve (CN). Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), immunofluorescence and Masson's trichrome staining were used to verify the related factors and protein expression levels.
Results
We found that NO2-OA could significantly increase erectile pressure in the corpus cavernosum of DMED rats. Results of western blot, confocal immunofluorescence and qRT-PCR assays revealed that NO2-OA significantly reduced inflammatory factors and the expression of nuclear factor kappa B (NF-κB). In addition, Masson staining results indicated that NO2-OA significantly reduced the display of fibrotic tissue in the corpus cavernosum. These beneficial effects may be related to reductions in the expression of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) and the increase in the expression of α-smooth muscle actin (α-SMA). Finally, NO2-OA treatment increased the expression of the autophagy marker, LC3, while P62 was decreased, effects suggesting that one of the underlying mechanisms of NO2-OA may involve an activation of the PI3K/AKT/mTOR pathway to enhance the capacity for autophagy within this tissue. Conclusions: NO2-OA enhances erectile function within a rat model of DMED by inhibiting inflammation and fibrosis along with activating autophagy.