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Sources of Funding: This work was supported by grants from the National Natural Science Foundation of China (NSFC #81471451)

Introduction

Soluble epoxide hydrolase (sEH) can catalyze epoxyeicosatrienoic acids (EETs) to dihydroxyepoxytrienoic acids (DHETs), thereby reduces their biological activity, such as vasodilation and anti-apoptosis. We performed this study to investigate the effect of inhibition of sEH on the diabetic erectile dysfunction in mice.

Methods

Diabetes was induced in 8-week old male mice by introperitoneal injection of streptozotocin with the dose of 60mg/kg for 5 consecutive days. 16 weeks after the induction the mice were divided into 3 groups (8 mice in each group): (1) nondiabetic control group, (2) diabetic mice + vehicle group which were given tap water containing 0.01% DMSO for 4 weeks, and (3) diabetic mice + trans-4-[4- (3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t- AUCB) group, which received t- AUCB (an inhibitor of sEH, 2mg/L in drinking water containing 0.01% DMSO) for 4 weeks. Then erectile function of mice was measured by electrical stimulation of the cavernous nerve and ratio between intracavernosal pressure (ICP) and mean systemic arterial blood pressure (MAP) at the peak of erectile response was calculated. After that penis tissue was harvested. Expression of sEH, transforming growth factor beta 1 (TGF?-1) and collagen IV in corpus cavernosum were measured by western blot. The deposition of extracellular collagen was determined by Masson trichrome staining, while the content of ?-smooth muscle actin (?-SMA) was measured by immunofluorescence. Apoptosis was detected by terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL).

Results

The ICP/MAP was reduced in diabetic mice compared with control group, but was improved by t-AUCB treatment (p<0.05). The expression of sEH, TGF?-1 and collagen IV were all decreased by giving t-AUCB in diabetic mice (p<0.05). The ratio of smooth muscle to collagen and the content of ?-SMA were both increased in t-AUCB group compared with vehicle group (p<0.05). Besides, less apoptotic cells were found in t-AUCB group than in the vehicle group (p<0.05).

Conclusions

sEH might play a role in the development of diabetic erectile dysfunction. Inhibition of sEH could improve the erectile function in diabetic mice by reducing the fibrosis and apoptosis in corpus cavernosum.

Funding

This work was supported by grants from the National Natural Science Foundation of China (NSFC #81471451)