title: Low-intensity Pulsed Ultrasound Improves Erectile Function in Streptozotocin-induced Type I Diabetic Rats.
abstract: OBJECTIVE
  To investigate the effect of low-intensity pulsed ultrasound (LIPUS) as a treatment for erectile dysfunction (ED) in a rat model of type I diabetes mellitus (DM) induced by streptozotocin (STZ).
  
  
  METHODS
  Seventy male Sprague-Dawley rats were randomly assigned to 2 cohorts: a normal control (NC) group and an STZ-induced DM group, which was further subdivided into DM, DM+LIPUS 100, DM+LIPUS 200, and DM+LIPUS 300 groups and a DM+LESWT (low-energy shock wave therapy) 300 positive control group. Animals in the LIPUS subgroups were treated at different energy levels (100, 200, and 300 mW/cm(2)) for 3 minutes, and animals in the LESWT group received 300 shocks at 0.09 mJ/mm(2). All procedures were repeated 3 times per week for 2 weeks. After a 2-week wash-out period, intracavernous pressure (ICP) was measured; the midpenile region was examined histologically; and VEGF, αSMA, eNOS, and nNOS expression, and activity of the TGF-β1/Smad/CTGF signaling pathway were examined in penile tissue by Western blot analysis.
  
  
  RESULTS
  LIPUS therapy significantly improved erectile function in diabetic rats, as evidenced by enhanced ICP levels, increased endothelial and smooth muscle content, a higher collagen I/collagen III ratio, increased quantity of elastic fibers, and elevated eNOS and nNOS expression. Interestingly, LIPUS was also associated with downregulation of the TGF-β1/Smad/CTGF signaling pathway in penile tissue, whose activation is correlated with ED pathology.
  
  
  CONCLUSIONS
  LIPUS therapy improved erectile function and reversed pathologic changes in penile tissue of STZ-induced diabetic rats. LIPUS therapy has potential as a noninvasive therapy for diabetic ED in the clinic.
authors.affiliation: Andrology Center, Peking University First Hospital, Peking University, Beijing, China.
authors.forename: Hongen
authors.initials: H
authors.lastname: Lei
authors.affiliation: Department of Ophthalmology, Beijing ChaoYang Hospital, Capital Medical University, Beijing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xin
authors.affiliation: Andrology Center, Peking University First Hospital, Peking University, Beijing, China.
authors.forename: Ruili
authors.initials: R
authors.lastname: Guan
authors.affiliation: Andrology Center, Peking University First Hospital, Peking University, Beijing, China.
authors.forename: Yongde
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Andrology Center, Peking University First Hospital, Peking University, Beijing, China; Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA.
authors.forename: Huixi
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Urology, The Second Hospital of Jilin University, Jilin University, Changchun, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Tian
authors.affiliation: Andrology Center, Peking University First Hospital, Peking University, Beijing, China; Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Andrology Center, Peking University First Hospital, Peking University, Beijing, China.
authors.forename: Zhezhu
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Andrology Center, Peking University First Hospital, Peking University, Beijing, China.
authors.forename: Yinglu
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA.
authors.forename: Tom F
authors.initials: TF
authors.lastname: Lue
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA.
authors.forename: Guiting
authors.initials: G
authors.lastname: Lin
authors.affiliation: Andrology Center, Peking University First Hospital, Peking University, Beijing, China. Electronic address: xinzc@bjmu.edu.cn.
authors.forename: Zhongcheng
authors.initials: Z
authors.lastname: Xin
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000150:complications*; D004727:Endothelium / Q000473:pathology; D007172:Erectile Dysfunction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D005355:Fibrosis; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010413:Penis / Q000473:pathology / Q000503:physiopathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D013311:Streptozocin; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D000069453:Ultrasonic Waves; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000199:Actins; D055513:Connective Tissue Growth Factor; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D051785:Smad Proteins; D013311:Streptozocin; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; C526316:CCN2 protein, rat; C498862:Acta2 protein, rat; C496316:Nos3 protein, rat