(097) A Novel Therapeutic Strategy for Recovery from Cavernous Veno-Occlusive Dysfunction through Chronic Administration of Hepatocyte Growth Factor and a JNK Inhibitor in a Rat Model of Cavernous Nerve Injury

Abstract

Abstract Introduction Structural alterations of penis including cavernosal apoptosis and fibrosis induce venous leakage in the corpus cavernosum or cavernosal veno-occlusive dysfunction, a key pathophysiology of erectile dysfunction (ED) after radical prostatectomy. Objective We aimed to determine if JNK inhibition in combination with intracavernosal administration of hepatocyte growth factor (HGF) would completely restore cavernosal veno-occlusive function (CVOF) in a rat model of ED induced by bilateral CN crush injury (CNCI). Methods A total of forty-two male Sprague-Dawley rats were randomly assigned to sham control (S), CNCI (I) and CNCI treated with combination of JNK inhibitors and HGF (J+H) for 5 weeks after surgery. All rats in each group were evaluated by dynamic infusion cavernosometry (DIC), caspase-3 activity assay, Masson’s trichrome staining, immunohistochemical staining of α-smooth muscle actin (α-SMA) and immunoblotting at 5 weeks after surgery. Results Regarding CVOF, Group I showed a decreased papaverine response, an increased maintenance and drop rates compared to Group S. Group J+H showed significant improvements in the three DIC parameters compared to Group I. There were no differences in papaverine response and drop rate between Group J+H and Group S. Regarding the structural integrity of corpus cavernosum, Group I had an increased caspase-3 activity, decreased SM/collagen ratio, decreased content of SM, decreased protein expression of PECAM-1, and decreased phosphorylation of c-Jun and c-Met. Group J+H had significant alleviation in the histological and molecular derangement compared to Group I. There were no differences in caspase-3 activity, SM content, PECAM-1 protein expression, c-Jun phosphorylation and c-Met phosphorylation between Group J+H and Group S. Conclusions Our data indicate that chronic administration of JNK inhibitors and HGF may restore CVOF to the level comparable to sham control level through preservation of structural integrity of the corpus cavernosum. Combination of JNK inhibition and HGF might be a potential therapeutic option for recovering from CVOD. Disclosure No