Melatonin receptor-mediated ameliorative effect against erectile dysfunction in rats with streptozotocin-induced type 1 diabetes
Tang, Z1; Cui, K1; Song, JY1; Ruan, YJ1; Wang, T1; Yang, J1; Wang, SG1; Liu, JH2
1: Tongji Hospital, Tongji Medical College, HUST, China; 2: Tongji Hospital, Tongji Medical College, HUST, ChinaTongji Hospital, Tongji Medical College, HUST, China
Objective: Considering 35%–90% of patients with diabetes mellitus (DM) suffer erectile dysfunction (ED), which starts about 10–15 years earlier than in the population without DM. Moreover, these patients showed a poor response to the first-line oral phosphodiesterase type 5 inhibitors. Thus, a novel treatment method is urgently needed. We tried to demonstrate whether melatonin could improve erectile function in diabetic rats and the underlying mechanisms.
Methods: Type 1 DM was induced by using streptozotocin. 8 weeks later, we conducted an apomorphine test to confirm diabetes mellitus erectile dysfunction (DMED). Only rats with DMED (n=20) were administered melatonin (n=10) in a dose of 10mg/kg or vehicle (n=10) intraperitoneally each day for 4 weeks, rats as control group (n=10) were fed in the same condition for 4 weeks. Then, cavernous nerve electrostimulation was used to evaluate the erectile function of all rats. Histologic and molecular alterations of the corpus cavernosum also were analyzed. Furthermore, corpus cavernosum smooth muscle cells of rats were cultured under different conditions: normal glucose (NG), high glucose (HG), high glucose + melatonin (HG+M), high glucose + melatonin + melatonin receptor antagonist luzindole(HG+M+L), and related molecular biological parameter were detected.
Results: Compared with the control group and the melatonin-treated group, the DMED group showed (1) lower erectile function: lower intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio and lower total ICP (area under curve, AUC); (2) higher levels of ROS and MDA, but lower levels of SOD activity; (3) higher levels of apoptosis proved by the expression levels of Bax, Bcl-2, caspase 3 and apoptosis index; (4) In vitro study demonstrated that melatonin treatment increased Bcl-2 expressions, and p-eNOS/eNOS ratio and decreased p-gp91, Bax, and caspase-3 expressions. However, these protective eﬀects conferred by melatonin were partially blocked by luzindole (the antagonist of melatonin membrane receptors).
Conclusion: Melatonin supplementation improved erectile function of diabetic rats via inhibiting oxidative stress and apoptosis in a receptor-dependent manner. Our finding provided evidences for a potential therapy method for DMED.
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