Lee Seung-Ryeol, Kim Ki-Ho, You Ho-Song, Fu Johnny, Hsieh Tung-Chin Mike, Bhargava Valmik, Raj Rajasekaran M
Departments of Urology and Medicine, VA San Diego Health Care System University of California, San Diego, California.
Department of Urology, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
Physiol Rep. 2017 Nov;5(21). doi: 10.14814/phy2.13481.
Current technology for penile hemodynamic evaluations in small animals is invasive and has limitations. We evaluated a novel laser speckle contrast imaging (LSCI) technique to determine age-related changes in penile microvascular perfusion (PMP) and tested the role of cavernosal muscle (CC) fibrosis mediated by Wnt-TGF 1 signaling pathways in a mouse model. Ten young (2-3 months) and old (24-28 months) wild-type C57BL6 male mice were subjected to PMP measured using a LSCI system. Penile blood flow (PBF, peak systolic velocity, PSV) was also measured using a color Doppler ultrasound for comparison. Measurements were made before and after injection of vasoactive drugs: prostaglandin E (PGE) and acetylcholine (ACh). CC was processed for immunohistochemical studies for markers of endothelium and fibrosis. Protein levels were quantified by Western blot.PMP and PBF increased significantly from baseline after injection of vasoactive drugs. Peak PMP after PGE and ACh was higher in young mice (225.0 ± 12.0 and 211.3 ± 12.1 AU) compared to old (155.9 ± 7.1 and 162.6 ± 5.1 AU, respectively). PSV after PGE was higher in young than old mice (112.7 ± 8.5 vs. 78.2 ± 4.6 mm/sec). PSV after ACh was also higher in young (112.7 ± 5.6 mm/sec) than older mice (69.2 ± 7.1 mm/sec). PMP positively correlated with PSV ( = 0.867, = 0.001). Immunostaining and Western blot showed increased protein expression of all fibrosis markers with aging. LSCI is a viable technique for evaluating penile hemodynamics. Increased cavernosal fibrosis may cause impaired penile hemodynamics and increased incidence of erectile dysfunction in older men.
目前用于小动物阴茎血流动力学评估的技术具有侵入性且存在局限性。我们评估了一种新型激光散斑对比成像（LSCI）技术，以确定阴茎微血管灌注（PMP）与年龄相关的变化，并在小鼠模型中测试了由Wnt-TGF 1信号通路介导的海绵体肌（CC）纤维化的作用。对10只年轻（2 - 3个月）和年老（24 - 28个月）的野生型C57BL6雄性小鼠进行PMP测量，使用LSCI系统进行检测。还使用彩色多普勒超声测量阴茎血流量（PBF，收缩期峰值流速，PSV）以作比较。在注射血管活性药物前列腺素E（PGE）和乙酰胆碱（ACh）之前和之后进行测量。对CC进行处理，用于内皮和纤维化标志物的免疫组织化学研究。通过蛋白质印迹法定量蛋白质水平。注射血管活性药物后，PMP和PBF较基线显著增加。与年老小鼠（分别为155.9±7.1和162.6±5.1 AU）相比，年轻小鼠注射PGE和ACh后的峰值PMP更高（分别为225.0±12.0和211.3±12.1 AU）。年轻小鼠注射PGE后的PSV高于年老小鼠（112.7±8.5对78.2±4.6毫米/秒）。年轻小鼠注射ACh后的PSV也高于年老小鼠（112.7±5.6毫米/秒对69.2±7.1毫米/秒）。PMP与PSV呈正相关（r = 0.867，P = 0.001）。免疫染色和蛋白质印迹显示，随着年龄增长，所有纤维化标志物的蛋白质表达增加。LSCI是评估阴茎血流动力学的一种可行技术。海绵体纤维化增加可能导致老年男性阴茎血流动力学受损和勃起功能障碍发生率增加。
