期刊
BJU INTERNATIONAL
卷 111, 期 1, 页码 159-170出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1464-410X.2012.11278.x
关键词
bilateral cavernosal nerve resection; GFR-alpha 2; main pelvic ganglia; neurturin; nNOS; sildenafil
资金
- National Institute of Neurological Disorders and Stroke
- National Institute of General Medicine NINDS/NIGMS [SC1NS064611]
- National Center for Research Resources (NCRR) [1U54RR026138]
- Research Centers in Minority Institutions, Translational Research Network (RTRN) [U54RR022762]
- NATIONAL CENTER FOR RESEARCH RESOURCES [U54RR022762, U54RR026138] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [SC1NS064611] Funding Source: NIH RePORTER
- National Institute on Minority Health and Health Disparities [U54MD007598, S21MD000103, U54MD008149] Funding Source: NIH RePORTER
Objective To determine the gene expression profile of pelvic ganglia neurones after bilateral cavernosal nerve resection (BCNR) and subsequent treatment with sildenafil in relation to neurotrophic-related pathways. Materials and Methods Fisher rats aged 5 months were subjected to BCNR or sham operation and treated with or without sildenafil (20 mg/kg body-weight in drinking water) for 7 days. Total RNA isolated from pelvic ganglia was subjected to reverse transcription and then to quantitative reverse transcriptase-polymerase chain reaction (PCR) with the RAT-neurotrophic array. Results were corroborated by real-time PCR and western blotting. Another set of animals were injected with a fluorescent tracer at the base of the penis, 7 days before BCNR or sham operation, and were sacrificed 7 days after surgery. Sections of pelvic ganglia were used for immunohistochemistry with antibodies against neurturin, neuronal nitric oxide synthase, tyrosine hydroxylase and glial cell line-derived neurotrophic factor receptor alpha 2. Results A down-regulation of the expression of neuronal nitric oxide synthase accompanied by changes in the level of cholinergic neurotrophic factors, such as neurturin and its receptor glial cell line-derived neurotrophic factor receptor alpha 2, artemin, neurotrophin-4 and cilliary neurotrophic factor, was observed 7 days after BCNR in pelvic ganglia neurones. Treatment with sildenafil, starting immediately after surgery, reversed all these changes at a level similar to that in sham-operated animals. Conclusions Sildenafil treatment promotes changes in the neurotrophic phenotype, leading to a regenerative state of pelvic ganglia neurones. The present study provides a justification for the use of phosphodiesterase 5 inhibitors as a neuroprotective agent after BCNR.
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