Jeon Seung Hwan, Bae Woong Jin, Zhu Guan Qun, Tian Wenjie, Kwon Eun Bi, Kim Ga Eun, Hwang Sung Yeoun, Lee Kyu Won, Cho Hyuk Jin, Ha U-Syn, Hong Sung-Hoo, Lee Ji Youl, Kim Sae Woong
Department of Urology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Catholic Integrative Medicine Research Institute, The Catholic University of Korea, Seoul, Republic of Korea.
Transl Androl Urol. 2020 Apr;9(2):416-427. doi: 10.21037/tau.2020.01.23.
A Korean herbal formulation named KH-204 was reported to have an antioxidant effect in our previous study. We hypothesized that Low-intensity extracorporeal shockwave therapy (Li-ESWT) combined with KH-204 would accelerate the treatment of erectile dysfunction (ED) by enhancing antioxidant. We investigated the synergistic effect of Li-ESWT and KH-204 for ED and explored the mechanism.
Human umbilical vein endothelial cells (HUVEC) were treated with KH-204 and LI-ESWT in vitro. Fifty 5-week-old male Sprague Dawley rats received an intraperitoneal injection of 5-ethynyl-20-deoxyuridine (EdU) which can label live cells, and were randomly divided into five groups: (I) normal; (II) diabetes mellitus-associated erectile dysfunction (DMED); (III) DMED + KH-204; (IV) DMED + Li-ESWT; and (V) DMED + KH-204/Li-ESWT. Li-ESWT treatment was repeated three times a week every other day for four weeks in group 4 and 5. Meanwhile, rats in group 3 and 5 were orally fed 400 mg/kg of KH-204 daily for 1 month. Following a 1-week washout period, penile tissues were evaluated by immunostaining and Western blotting.
KH-204 combined with Li-ESWT improved intracavernosal pressure (ICP) in DMED rats. Li-ESWT/KH-204 stimulated HUVEC tube formation and promoted proliferation. Li-ESWT drove progenitor cells to migrate to penile tissue and KH-204 protected penile progenitor cells in the corpus cavernosum. Oxidative stress was relieved by KH-204/Li-ESWT. Treatment with KH-204/Li-ESWT protected penile progenitor cells, which were recruited to the corpus cavernosum by Li-ESWT, from apoptosis via its antioxidant activity. KH-204/Li-ESWT protected penile tissue from oxidative stress by improving the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), increasing superoxide dismutase (SOD), decreasing 8-hydroxy-20-deoxyguanosine (8-OHdG), and reducing apoptosis. KH-204/Li-ESWT promoted stromal derived factor-1 (SDF-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1) in DMED rats.
KH-204 protected penile progenitor cells, which were recruited to the corpus cavernosum by Li-ESWT, from apoptosis via its antioxidant activity. The combination of Li-ESWT and KH-204 as a synergy therapy could be a potential and effective treatment for DMED.
在我们之前的研究中，一种名为KH - 204的韩国草药配方被报道具有抗氧化作用。我们推测低强度体外冲击波疗法（Li - ESWT）联合KH - 204可通过增强抗氧化作用加速勃起功能障碍（ED）的治疗。我们研究了Li - ESWT和KH - 204对ED的协同作用并探索其机制。
在体外用人脐静脉内皮细胞（HUVEC）进行KH - 204和Li - ESWT处理。五十只5周龄雄性Sprague Dawley大鼠接受腹腔注射可标记活细胞的5 - 乙炔基 - 2′ - 脱氧尿苷（EdU），并随机分为五组：（I）正常组；（II）糖尿病相关性勃起功能障碍（DMED）组；（III）DMED + KH - 204组；（IV）DMED + Li - ESWT组；（V）DMED + KH - 204/Li - ESWT组。第4组和第5组每隔一天进行一次Li - ESWT治疗，每周重复三次，共四周。同时，第3组和第5组大鼠每天口服400 mg/kg的KH - 204，持续1个月。经过1周的洗脱期后，通过免疫染色和蛋白质印迹法评估阴茎组织。
KH - 204联合Li - ESWT改善了DMED大鼠的海绵体内压（ICP）。Li - ESWT/KH - 204刺激HUVEC管形成并促进增殖。Li - ESWT促使祖细胞迁移至阴茎组织，而KH - 204保护海绵体中的阴茎祖细胞。KH - 204/Li - ESWT减轻了氧化应激。KH - 204/Li - ESWT治疗通过其抗氧化活性保护被Li - ESWT募集到海绵体的阴茎祖细胞免于凋亡。KH - 204/Li - ESWT通过改善核因子红细胞2相关因子2（Nrf2）/血红素加氧酶 - 1（HO - 1）的表达、增加超氧化物歧化酶（SOD）、降低8 - 羟基 - 2′ - 脱氧鸟苷（8 - OHdG）以及减少凋亡来保护阴茎组织免受氧化应激。KH - 204/Li - ESWT促进了DMED大鼠的基质细胞衍生因子 - 1（SDF - 1）和血小板内皮细胞黏附分子 - 1（PECAM - 1）。
KH - 204通过其抗氧化活性保护被Li - ESWT募集到海绵体的阴茎祖细胞免于凋亡。Li - ESWT与KH - 204联合作为一种协同疗法可能是治疗DMED的一种潜在有效方法。
