Effect Of Probucol On PRMT1/DDAH/ADMA/NOS Pathway In The Penile Tissue Of Diabetic Rats

Objective ①To create the diabetic induced erectile dysfunction rat model; ②To elucidate the effects of PRMT1/DDAH/ADMA/NOS pathway in corpus cavernosum of diabetic rats and the structure changes of corpus cavernosum; ③To investigate the underlying mechanisms of probucol on erectile function, so as to provide theoretieal bases for ameliorating erectile dysfunction.MethodsDiabetes were induced in 20 SD rats by intraperitoneal injection of streptozotocin (60 mg/Kg), in which 18 DM rats were accompanied with erectile dysfunction by detecting apomorphine-induced erections. Diabetic rats were then randomly divided into the diabetic mellitus group (n=9) and the probucol group (n= 9) with daily gavage feedings of probucol at doses of 300mg/kg for 12 weeks. None diabetic SD rats were used as controls (n=10). After 12 weeks, the fasting plasma glucose and weight were determined, then the erectile function of the rats were assessed through measuring the mean arterial pressure (MAP) and the maximal intracavernous pressure (Max ICP). The protein levels of PRMT1, DDAH1, DDAH2, eNOS, nNOS and a-SMA were evaluated by immunohistochemistry and Western blot. The levels of ADMA and cGMP in corpus cavernosum were assessed by ELISA. The contents of MDA and the activities of SOD in corpus cavernosum were also detected. The structure changes of corpus cavernosum were revealed by Masson’s trichrome stain.Results Compared with control group, the Max ICP/MAP, the levels of DDAH1, DDAH2, eNOS, nNOS and α-SMA, the cGMP contents and the activities of SOD in the diabetic mellitus group were significantly decreased (all P<0.05), while the levels of ADMA and MDA and the degree of cavernous tissue fibrosis were significantly increased (all P<0.05). Compared with the diabetic mellitus group, the Max ICP/MAP, the levels of DDAH1, DDAH2, eNOS, nNOS and a-SMA, the cGMP contents and the activities of SOD in the probucol group were significantly increased (all P<0.05), while the levels of ADMA and MDA and the degree of cavernous tissue fibrosis were significantly decreased (all P< 0.05).Conclusion①PRMT1/DDAH/ADMA/NOS metabolism pathway may contribute to erectile dysfunction in diabetic induced rats. ②Probucol treatment could ameliorate erectile function in diatebic rats via regulation of PRMT1/DDAH/ADMA/NOS metabolism pathway by inhibiting oxidative stress.③The degree of cavernous tissue fibrosis may also contribute to erectile dysfunction in diabetic induced rats.