Effect of probucol on autophagy and apoptosis in the penile tissue of streptozotocin-induced diabetic rats.

Abstract

Autophagy and apoptosis have been regarded as important processes in the development of diabetic erectile dysfunction (DMED). Probucol is considered to have anti-apoptotic effects, but its relationship with autophagy has not been reported. The aim of this study was to investigate the effects and mechanisms of probucol on erectile function. Thirty Sprague–Dawley (SD) male rats (12 weeks old) were fasted for 12 h. Twenty SD rats were injected with a single intraperitoneal injection of 60 mg kg−1 streptozotocin (STZ). Ten rats were given vehicle only and used as a sham group. After 72 h, 20 STZ-treated rats with random blood glucose concentrations consistently greater than 16.7 mmol l−1 were used as successfully established diabetic rats. The diabetic rats were divided randomly into two groups and treated with a daily gavage of probucol at a dose of 0 or 500 mg kg−1 for 12 weeks. After treatment, the intracavernous pressure (ICP) was used to measure erectile function upon electrical stimulation of the cavernous nerve. After euthanasia, penile tissue was examined using immunohistochemistry and Western blot to assess the protein levels of B-cell lymphoma-2 (Bcl-2), BCL2-associated X (Bax), microtubule-associated protein light chain 3-II (LC3-II), mammalian target of rapamycin (mTOR), and sequestosome 1 (P62). Caspase-3 activity was measured to determine apoptosis using a caspase-3 assay kit. After 12 weeks of treatment, the erectile function of the probucol group was significantly better than that of the DM group (P < 0.05). Bax and LC3-II protein expression and caspase-3 activity were significantly lower in the probucol group than those in the DM group (all P < 0.05), while Bcl-2, mTOR, and P62 protein expression levels were significantly higher than those in the DM group (all P < 0.05). We demonstrated that probucol inhibited apoptosis and autophagy in STZ-induced diabetic rats.