Status Plus




Inhibition of microRNA-92a improved erectile dysfunction in streptozotocin-induced diabetic rats via suppressing oxidative stress and endothelial dysfunction

Tang, Z1; Yang, J1; Yu, Z1; Cui, K1; Wang, T1; Wang, SG1; Liu, JH1

1: Tongji 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. In previous study, we found that miR-92a was significantly upregulated in diabetic rats. Our study aimed at exploring the effect of microRNA-92a-3p (miR-92a) antagomir on erectile dysfunction (ED) in streptozotocin (STZ)-induced diabetic rats and the potential mechanisms.

Methods: Type 1 DM was induced by using streptozotocin. 8 weeks later, we conducted an apomorphine test to confirm diabetes mellitus related erectile dysfunction (DMED). Rats with DMED were divided into 3 groups with 10 rats in each group: DMED, DMED + miR-92a antagomir, DMED + sildenafil, and rats as control group (n=10) were fed in the same condition. 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, endothelial cells of rat aorta were cultured in vitro under different conditions: normal glucose (NG), high glucose (HG), high glucose + miR-92a mimic (HG + mimic), high glucose + miR-92a inhibitor (HG + inhibitor), and related molecular biological parameter were detected.

Results: Compared with the other three groups, 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) lower expression levels of eNOS/NO/cGMP signaling pathway; (3) lower expression levels of heme oxygenase-1 (HO-1) (4) Experiment in vitro demonstrated that miR-92a was upregulated in HG group, overexpression of miR-92a (HG + mimic) impairs endothelial function, and inhibition of miR-92a (HG + inhibitor) could increase the ratio of p-eNOS/eNOS and the expression levels of HO-1.

Conclusion: Our study provides evidence that miR-92a was upregulated in diabetic rats and in endothelial cells of rat aorta under HG condition. miR-92a inhibition improved erectile function through inhibiting endothelial dysfunction and oxidative stress via increasing the expression levels of eNOS/NO/cGMP and HO-1. Our results showed the ameliorative effect of miR-92a inhibition in diabetic ED and provided a new potential therapy method.


Work supported by industry: no.

Go Back