Nitro-oleic acid (NO 2 -OA) ameliorates erectile dysfunction in a rat model of diabetes mellitus via modulation of fibrosis, inflammation and autophagy

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 (NO -OA) in a streptozotocin-induced rat model of DMED was evaluated. Sixty rats were randomly divided into four groups: control, DMED, DMED + Vehicle and DMED + NO -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 NO -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. We found that NO -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 NO -OA significantly reduced inflammatory factors and the expression of nuclear factor kappa B (NF-κB). In addition, Masson staining results indicated that NO -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, NO -OA treatment increased the expression of the autophagy marker, LC3, while P62 was decreased, effects suggesting that one of the underlying mechanisms of NO -OA may involve an activation of the PI3K/AKT/mTOR pathway to enhance the capacity for autophagy within this tissue. NO -OA enhances erectile function within a rat model of DMED by inhibiting inflammation and fibrosis along with activating autophagy.