Abstract

Introduction Erectile dysfunction (ED), which is common in patients with diabetes mellitus (DM), seriously affects quality of life . Previous studies on the treatment of DM–induced ED (DMED) involve autophagy, but the specific effect and mechanism of treatment are not yet clear. Aim To investigate the effect and mechanism of rapamycin , an autophagy inducer, in ameliorating DMED. Methods 45 male Sprague-Dawley rats (7 weeks old) were used in the experiment. 8 rats were randomly selected as the control group; the other rats were treated with streptozotocin to induce type 1 DM . After 10 weeks, an apomorphine test was used to confirm DMED. Rats with DMED were intraperitoneally injected with rapamycin or vehicle for 3 weeks. Rats in the control group were injected with saline. Erectile function in rats was measured by electrically stimulating the cavernous nerve. The penises were then harvested for histologic examinations, ribonucleic acid (RNA), and protein levels of related factors by immunohistochemistry , immunofluorescence, real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blot . Main Outcome Measure Erectile function was evaluated by maximum intracavernous pressure and mean arterial pressure . Penile tissues were used to perform histologic examinations and to determine the RNA and protein levels. Results Erectile function, which was impaired in rats with DMED, was significantly ameliorated in the DMED + rapamycin group. The nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway was inhibited in the DMED group, and rapamycin significantly reduced this inhibition. The DMED group showed increased autophagy and apoptosis level compared with the non-diabetic group, and rapamycin increased the autophagy level and decreased the apoptosis level in the penis. Penile fibrosis was more severe in the DMED group than in the control group and was partially but significantly improved in the DMED + rapamycin grou