ED 17. Effects of icariin on improving erectile function in Streptozotocin - induced diabetic rats

Introduction: Icariin has been shown to improve penile hemodynamics in animal models of erectile dysfunction from cavernous nerve injury and castration. The effects of icariin on penile hemodynamics in diabetic animals remain to be determined. Transforming growth factorβ1 (TGFβ1) has been implicated in the pathogenesis of diabetes-related erectile dysfunction. Aim: To investigate the effects of icariin in the penis of Streptozotocin (STZ)-induced diabetic rat.

Methods: 2-month-old Sprague-Dawley male rats received onetime intraperitoneal (IP) STZ (60 mg/kg) or vehicle injection after a 16 hours fast. Three days later, the STZ-induced diabetic rats were randomly divided into 4 groups and treated with daily gavage feedings of a 50:50 mix of normal saline and Dimethyl sulfoxide (DMSO) or icariin dissolved in DMSO at doses of 1, 5 and 10 mg/kg for three months. A positive control group underwent IP injection of saline followed by daily gavage of saline/DMSO solution. Treatment was stopped one week prior to functional assay and euthanasia.

Main outcome measures: Penile hemodynamics were assessed by electrical stimulation of the cavernous nerves with real time intracavernous pressure (ICP) measurement. After euthanasia, penile tissue was studied using immunohistochemistry, Western blot, and ELISA to assess the NO-cGMP and TGFβ1/Smad2 signaling pathway.

Results: Diabetes attenuated ICP response in control animals. Untreated diabetic animals had decreased smooth muscle/ collagen ratio and endothelial cell content in the corpora cavernosa; treatment with icariin partially attenuated these effects. Icariin-treated animals also had a significantly greater expression of NADPH positive nerves and the endothelial cell marker, PECAM-1. TGFβ1/Smad2 signaling pathway was down-regulated in the penis from icariin-treated models relative to what was observed in negative control animals.

Conclusions: Icariin treatment preserved penile hemodynamics, smooth muscle and endothelial integrity, and nNOS expression in the penis of diabetic rats. Down-regulation of TGFβ1/Smad2 signaling pathway might mediate this effect.