132 Reduce Corporal Fibrosis to Protect Erectile Function by Inhibiting the Smad and Non-smad Pathway in the Aged Transgenic Rat Harboring Human Tissue Kallikrein 1

Our previous studies have demonstrated erectile function was preserved in aged transgenic rats (TGR) harboring the Human Kallikrein 1 (hKLK1), while the molecular level of hKLK1 reducing corporal fibrosis to inhibit aged-related dysfunction (ED) is poorly understood. Male wild-type Sprague-Dawley rats (WTR) and TGR harboring the hKLK1 gene were fed to 4 or 18 months old and divided into three groups: young WTR as the control, aged WTR (aWTR) and aged TGR (aTGR). Erectile function of all rats was assessed by cavernous nerve electrostimulation method. Masson’s trichrome was used to evaluate corporal fibrosis in the corpus cavernosum. Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) was conducted to detect the level of apoptosis in all rats. Immunohistochemistry, immunofluorescence, RT-PCR and western blot were used to detect the expression of target proteins. Compared with the yWTR group and aTGR group, the aWTR group showed: 1. Lower erectile function: the lower ratio of intracavernous pressure (ICP)/ mean arterial pressure (MAP); 2. Severe corporal fibrosis: the lower ratio of smooth muscle/collagen, the lower expression of α-SMA and the higher TGF-β; 3. Higher expression of Smad and non-Smad pathway: the higher expression of TGF-β/Smad/CTGF pathway and TGF-β/ROCK/LIMK2/Cofilin pathway. 4. Higher level of apoptosis: TUNEL showed higher level of apoptosis and expression of Bax, and lower Bcl-2.