World J Mens Health.  2017 Dec;35(3):186-195. 10.5534/wjmh.17024.

Effects of Next-Generation Low-Energy Extracorporeal Shockwave Therapy on Erectile Dysfunction in an Animal Model of Diabetes

• Jeong HC
• Jeon SH
• Qun ZG
• Kim KS
• Choi SW
• Bashraheel F
• Bae WJ
• Kim SJ
• Cho HJ
• Ha US
• Hong SH
• Lee JY
• Moon DG
• Kim SW

• KMID: 2398568
• DOI: http://doi.org/10.5534/wjmh.17024

Abstract

PURPOSE
Gene therapy, stem cell therapy, and low-energy extracorporeal shockwave therapy (ESWT) have been investigated as treatments for refractory erectile dysfunction (ED), but inconclusive evidence has been obtained. We investigated the effect of a next-generation electromagnetic cylinder ESWT device on an animal model of ED.
MATERIALS AND METHODS
Diabetes mellitus (DM)-induced rats were divided into 3 groups: group 1, control; group 2, DM; and group 3, DM+ESWT. Rats were treated with ESWT 3 times a week for 2 weeks. After the treatment course, intracavernous pressure was measured and the corpus cavernosum and cavernous nerve were evaluated.
RESULTS
In the DM group, all parameters predicted to be significantly lower in the ED model had statistically significantly decreased (p < 0.01). As a measurement of erectile function, intracavernous pressure was evaluated. The DM+ESWT group exhibited significantly restored erectile function compared to the DM group (p < 0.05). Moreover, ESWT treatment restored smooth muscle content, as assessed by Masson's trichrome staining (p < 0.05). Finally, corporal tissue and the dorsal nerve were evaluated by immunohistochemistry, Western blotting, and ELISA. After ESWT treatment, vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), platelet endothelial cell adhesion molecule-1, cyclic guanosine monophosphate, and neuronal nitric oxide synthase (nNOS) expression levels were restored to levels in the DM group (p < 0.05).
CONCLUSIONS
Electromagnetic cylinder ESWT device resulted in increased VEGF, nNOS, and eNOS expression; reduced smooth muscle atrophy; and increased endothelial cell regeneration in a DM-associated ED model. Our data suggest that safe and effective application could be possible in future clinical studies.

Keyword

Animals; Diabetes mellitus; Erectile dysfunction; Vascular endothelial growth factor

MeSH Terms

Animals*
Antigens, CD31
Atrophy
Blotting, Western
Diabetes Mellitus
Endothelial Cells
Enzyme-Linked Immunosorbent Assay
Erectile Dysfunction*
Genetic Therapy
Guanosine Monophosphate
Immunohistochemistry
Magnets
Male
Models, Animal*
Muscle, Smooth
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type III
Rats
Regeneration
Stem Cells
Vascular Endothelial Growth Factor A
Antigens, CD31
Guanosine Monophosphate
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type III
Vascular Endothelial Growth Factor A

Figure

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  Fig. 1 Extracorporeal shockwave therapy (MT2000H) application to the rat penis. Under anesthesia, the prepuce was degloved and sutured to fix it.

• 

  Fig. 2 Intracavernosal pressure (ICP), ICP/mean arterial pressure (MAP), and area under the curve (AUC)/MAP measurements of each group. (A) ICP recordings after cavernous nerve stimulation. (B) Comparison of ICP/MAP ratios of the different groups. (C) Comparison of AUC/MAP ratios. Data are expressed as mean±standard deviation. aStatistical significance in comparison with the diabetes mellitus (DM)+extracorporeal shockwave therapy (ESWT) group. bStatistical significance in comparison with the DM group.

• 

  Fig. 3 Smooth muscle content evaluation of each group by Masson's trichrome staining (×100). The graph shows comparison of the smooth muscle and collagen fiber ratios of the different groups. Data are expressed as mean±standard deviation. aStatistical significance in comparison with the diabetes mellitus (DM)+extracorporeal shockwave therapy (ESWT) group. bStatistical significance in comparison with the DM group.

• 

  Fig. 4 (A) Immunohistochemical staining (×200) of vascular endothelial growth factor (VEGF) expression in the corpus cavernosum of each group. The graph shows comparison of VEGF expression in the different groups. (B) Immunohistochemical staining (×400) of neuronal nitric oxide synthase (nNOS) expression in the dorsal penile nerve of each group. The graph shows a comparison of nNOS expression levels of the different groups. Data are expressed as mean±standard deviation. aStatistical significance in comparison with the diabetes mellitus (DM)+extracorporeal shockwave therapy (ESWT) group. bStatistical significance in comparison with the DM group.

• 

  Fig. 5 (A) Western blot images of platelet endothelial cell adhesion molecule-1 (PECAM-1).The graph shows a comparison of the relative PECAM-1/β-actin band densities of the different groups. (B) Pho-endothelial nitric oxide synthase (eNOS) expression in the corporal tissue of each group assessed by Western blotting. The graph shows a comparison of the relative band densities of Pho-eNOS/eNOS. (C) Cyclic guanosine monophosphate (cGMP) levels in the corporal tissue of each group as assessed by ELISA. Data are expressed as mean±standard deviation. aStatistical significance in comparison with the diabetes mellitus (DM)+extracorporeal shockwave therapy (ESWT) group. bStatistical significance in comparison with the DM group.

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