Juhyun Park1, Ji Sun Chai2, Soo Woong Kim2, Jae-Seung Paick2, Min Chul Cho3. 1. Department of Urology, Seoul National University College of Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea. 2. Department of Urology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea. 3. Department of Urology, Seoul National University College of Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea. Electronic address: cmc1206@empal.com.
Abstract
OBJECTIVE: To determine whether Jun N-terminal kinase (JNK) inhibition could alleviate erectile dysfunction (ED) through suppressing cavernosal apoptosis in a rat model of carvernosal nerve crush injury (CNCI), thereby providing potential therapeutic strategy for alleviating postradical prostatectomy ED. MATERIALS AND METHODS: Fifty-six 11-week-old male Sprague-Dawley rats were categorized equally into the following 4 groups: (1) sham surgery (S), (2) CNCI (I), (3) CNCI treated with low-dose JNK inhibitor (L), and (4) CNCI treated with high-dose JNK inhibitor (H). The L and H groups received daily intraperitoneal injection of JNK inhibitors (1.0 mg/kg for the L group and 10.0 mg/kg for the H group) for 2 weeks starting from the following day after surgery. Erectile response, Western blot, and immunohistochemistry were assessed. RESULTS: At 2 weeks after surgery, intracavernous pressure-mean arterial pressure and area under the curve-mean arterial pressure in group I were significantly decreased compared with those in group S. Erectile responses in group H were significantly improved compared with those in group I. Group I showed decreased smooth muscle (SM) content, increased apoptosis, increased apoptotic or SM cells positive for phosphorylated c-Jun, increased c-Jun phosphorylation, and decreased Bcl2-to-Bax ratio compared with group S. Group H showed significant improvements in histologic alterations and dysregulation of the JNK-driven pathway. CONCLUSION: Our data suggest that JNK inhibition can improve erectile function by alleviating cavernosal apoptosis through restoring the JNK-related pathway toward normal. Thus, an early therapeutic strategy targeting the JNK pathway might be able to alleviate cavernosal SM apoptosis and postradical prostatectomy ED caused by cavernous nerve injury.
OBJECTIVE: To determine whether Jun N-terminal kinase (JNK) inhibition could alleviate erectile dysfunction (ED) through suppressing cavernosal apoptosis in a rat model of carvernosal nerve crush injury (CNCI), thereby providing potential therapeutic strategy for alleviating postradical prostatectomy ED. MATERIALS AND METHODS: Fifty-six 11-week-old male Sprague-Dawley rats were categorized equally into the following 4 groups: (1) sham surgery (S), (2) CNCI (I), (3) CNCI treated with low-dose JNK inhibitor (L), and (4) CNCI treated with high-dose JNK inhibitor (H). The L and H groups received daily intraperitoneal injection of JNK inhibitors (1.0 mg/kg for the L group and 10.0 mg/kg for the H group) for 2 weeks starting from the following day after surgery. Erectile response, Western blot, and immunohistochemistry were assessed. RESULTS: At 2 weeks after surgery, intracavernous pressure-mean arterial pressure and area under the curve-mean arterial pressure in group I were significantly decreased compared with those in group S. Erectile responses in group H were significantly improved compared with those in group I. Group I showed decreased smooth muscle (SM) content, increased apoptosis, increased apoptotic or SM cells positive for phosphorylated c-Jun, increased c-Jun phosphorylation, and decreased Bcl2-to-Bax ratio compared with group S. Group H showed significant improvements in histologic alterations and dysregulation of the JNK-driven pathway. CONCLUSION: Our data suggest that JNK inhibition can improve erectile function by alleviating cavernosal apoptosis through restoring the JNK-related pathway toward normal. Thus, an early therapeutic strategy targeting the JNK pathway might be able to alleviate cavernosal SM apoptosis and postradical prostatectomy ED caused by cavernous nerve injury.
Authors: Qinyu Zeng; Shuhua He; Liren Zhong; Li Wang; Fengzhi Cheng; Haibo Zhang; Jialiang Hui; Anyang Wei Journal: Nan Fang Yi Ke Da Xue Xue Bao Date: 2019-11-30