title: Calpain Inhibition Improves Erectile Function in a Rat Model of Cavernous Nerve Injury.
abstract: BACKGROUND
  Erectile dysfunction (ED) after cavernous nerve (CN) injury remains difficult to treat. Calpain plays a critical role in causing neurodegenerative diseases. This study aimed to evaluate whether calpain inhibition preserves erectile function in a rat model of CN injury.
  
  
  METHODS
  Rats underwent sham surgery or CN crush injury. The CN-crushed rats were treated with vehicle or MDL-28170, a specific calpain inhibitor. At 1, 2, 3, and 7 days post-surgery, major pelvic ganglia (MPG) were harvested, followed by the measurement of erectile function, respectively. At 28 days, penile tissue and distal CN were harvested, followed by the measurement of erectile function in rats. Calpain activity in MPG and corpus cavernosum, as well as TGF-β1/Smad2 and collagen content in corpus cavernosum, were measured by western blot. Neuronal nitric oxide synthase (nNOS) was observed by immunohistochemistry.
  
  
  RESULTS
  Increased calpain activity was observed in MPG and corpus cavernosum. CN crush markedly attenuated the erectile responses and nNOS expression in CN, and these were improved by MDL-28170 treatment. Furthermore, treatment prevented increased TGF-β1/Smad2 and collagen expression in corpus cavernosum.
  
  
  CONCLUSIONS
  Our results suggested that calpain activation plays a role in pathogenesis of CN injury-associated ED. Calpain inhibition could be a novel approach for preventing the development of ED following CN injury.
authors: Department of Urology, the Central Hospital of Wuhan, Wuhan, Hubei, PR China.
authors: Zhi-Hua
authors: ZH
authors: Wan
authors: Guo-Hao
authors: GH
authors: Li
authors: Yong-Lian
authors: YL
authors: Guo
authors: Wen-Zhou
authors: WZ
authors: Li
authors: Lin
authors: L
authors: Chen
mesh_terms: D000818:Animals; D002154:Calpain / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004151:Dipeptides / Q000627:therapeutic use; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000188:drug therapy*; D006023:Glycoproteins / Q000627:therapeutic use; D007150:Immunohistochemistry; D008297:Male; D009409:Nerve Crush; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D017777:Parasympathetic Fibers, Postganglionic / Q000293:injuries*; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000473:pathology; D011468:Prostatectomy / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D051899:Smad2 Protein / Q000378:metabolism; D013049:Spectrin / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D004151:Dipeptides; D006023:Glycoproteins; D051899:Smad2 Protein; C497784:Smad2 protein, rat; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; C039304:calpain inhibitors; D013049:Spectrin; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D002154:Calpain; C058076:calpain inhibitor III