| Background:Diabetic erectile dysfunction(DMED)is mainly attributed to oxidative stress,and Nrf2 plays an important role in cellular antioxidation and regulates NO production in the vascular endothelium.Probucol maintains endothelial function through its antioxidant activity.Objective:To elucidate the effects of Nrf2/HO-1/DDAH/PPAR-y/eNOS pathway in corpus cavernosum of diabetic rats;③To provide theoretieal bases for ameliorating erectile dysfunction by investigating the mechanisms of probucol on erectile function.Methods:In our study,thirty 12-week-old Sprague-Dawley male rats were fasted for 12 hours.All rats received a 1-time injection of intraperitoneal streptozotocin(60mg/kg)or vehicle.After 72 hours,STZ-treated rats(with random blood glucose concentrations consistently greater than 16.7 mmol/L)were considered diabetic.The diabetic rats were randomly assigned into 2 groups and treated with daily gavage feedings of probucol at doses of 0 and 500 mg/kg for 12 weeks.A positive control group underwent intraperitoneal injection of normal saline followed by daily gavage of saline solution.Erectile function was assessed by electrical stimulation of the cavernous nerves with real-time intracavernous pressure measurement.After euthanasia,penile tissue was investigated using immunohistochemistry,Western blot,and ELISA to assess the proteins of Nrf2/HO-1/DDAH/PPAR-y/eNOS pathways.Results:After treatment,the rats in the probucol group presented significantly improved erectile function(P<0.05)than that of the diabetic group without probucol treatment(DM).Also,protein expression of Nrf2,DDAH,PPAR-y,HO-1 and eNOS was significantly higher than that of the DM group(P<0.05).CGMP concentrations and SOD concentrations of probucol-treated rats were higher than those of DM group(P<0.05).The MDA levels and ADMA levels were significantly lower than those of DM group rats(P<0.05).Conclusion:Probucol can improve erectile function via activation of Nrf2,which coordinates the HO-1/DDAH/PPAR-y/eNOS pathways in streptozotocin-induced diabetic rats.Background:Autophagy and apoptosis have been regarded important roles in the development of erectile dysfunction(ED).Probucol is considered to have anti-apoptotic mechanisms,but the relationship with autophagy has not been reported.The aim of this study was to investigate the effects and mechanisms of probucol on erecti e function.Objective ① To elucidate autophagy and apoptosis levels in the corpus cavernosum of diabetic rats.②To investigate the underlying mechanisms of probucol on erectile function.Methods:Thirty Sprague-Dawley male rats(12-week old)were fasted for 12 hours.20 SD rats were injected with a single intraperitoneal injection of 60 mg/kg STZ.10 rats were given vehicle only and used as sham group.After 72 hours,20 STZ-treated rats random blood glucose concentration were greater than 16.7mmol/L consistently,and diabetic rats were successfully established.The diabetic rats were divided into 2 groups randomly and were treated with daily gavage feedings of probucol at doses of 0 and 500 mg/kg for 12 weeks.After treatment,the intracavernous pressure(ICP)was used to measure erectile function by electrical stimulation of the cavernous nerve.After euthanasia,penile tissue was investigated using immunohistochemistry and Western blot to assess the protein of Bax,Bcl-2,LC3-Ⅱ,mTOR and P62.Caspase-3 activity was measured to determine apoptosis by Caspase-3 assay Kit(Biovision K106).Results:After 12 weeks treatment,the probucol group rats’ erectile function was significantly better than DM group rats(P<0.05).The protein expression of Bax and LC3-Ⅱ and Caspase-3 activity in probucol group were significantly lower than the DM group(P<0.05),while the protein expression of Bcl-2,mTOR and P62 were significantly higher than the DM group(P<0.05).Conclusion:We demonstrated that probucol inhibiting apoptosis and autophagy in STZ-induced diabetic rats. |
PDF Full Text Request