Abstract
INTRODUCTION: Activation of endogenous somatic stem cells (SSCs) might help conservation intrinsic healing capacity of a healthy organism as well as rejuvenation of damaged erectile function. AIM: The aim of this study is to investigate the feasibility and mechanism of icarisideII (ICAII) in the treatment of ED in a rat model of bilateral cavernous nerves (CN) injury. METHODS: Sixty newborn male rats were intraperitoneally injected with 5-ethynyl-2-deoxyuridine (EdU; 50 mg/kg) for the purpose of tracking endogenous SSCs. Eight weeks later, forty-eight rats underwent CN crush injury and were randomized into gavage feeding of solvent (vehicle group), ICAII 0.5, ICAII 1.5 or ICAII 4.5 mg/kg/day. Twelve animals underwent sham surgery, received vehicle treatment and served as sham group. Treatment was continued for 4 weeks followed by a wash-out period of 72 h. MAIN OUTCOME MEASURES: Intracavernous pressure (ICP). Immunofluorescence of neuropathology, smooth muscle cells (MSCs) atrophy and endogenous SSCs differentiation. Western blot of neuronal nitric oxide synthase (nNOS), α-SMA, and signaling pathway proteins. RESULTS: Daily gavage feeding of ICAII resulted in a significant improvement of erectile function compared to vehicle group. ICAII treatment partially prevented distortion of normal nerve anatomy, SMC loss and collagen deposition in the penis. More label retaining cells (LRCs) differentiated into Schwann cells and MSCs in ICAII treated rats than in vehicle controls. In addition, the trend of p38 mitogen activated protein kinase (MAPK) activity between groups was similar as that of EdU-positive cells. All these changes were caused by ICAII in a dose-dependent manner.