The effect of low‐intensity extracorporeal shockwave therapy in an obesity‐associated erectile dysfunction rat model
Objectives To investigate the feasibility of the Zucker fatty (ZF) rat as a model for research in to obesity‐associated erectile dysfunction (OAED) and to determine the effect of low‐intensity extracorporeal shockwave therapy (Li‐ESWT) on penile tissue and function in these rats. Materials and metho...
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| Veröffentlicht in: | BJU international 2018-07, Vol.122 (1), p.133-142 |
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| creator | Ruan, Yajun Zhou, Jun Kang, Ning Reed‐Maldonado, Amanda B. Tamaddon, Arianna Wang, Bohan Wang, Hsun Shuan Wang, Guifang Banie, Lia Lin, Guiting Liu, Jihong Lue, Tom F. |
| description | Objectives
To investigate the feasibility of the Zucker fatty (ZF) rat as a model for research in to obesity‐associated erectile dysfunction (OAED) and to determine the effect of low‐intensity extracorporeal shockwave therapy (Li‐ESWT) on penile tissue and function in these rats.
Materials and methods
Eight new‐born male Zucker lean (ZL group) rats (ZUC‐Leprfa 186) and 16 new‐born male ZF rats (ZUC‐Leprfa 185) were injected with 5‐ethynyl‐2’‐deoxyuridine (EdU) at birth to identify and monitor endogenous stem cells. Insulin tolerance testing was performed at 10 weeks of age. Beginning at 12 weeks of age, eight ZF rats were kept as controls, and the remaining eight ZF rats were treated with Li‐ESWT (0.02 mJ/mm2, 3 Hz, 500 pulses; ZF + SW group) twice a week for 4 weeks. Following a 1‐week washout period, erectile function was evaluated by measuring intracavernosal pressure (ICP) and mean arterial pressure (MAP). Penile tissues were then harvested for histological study to assess smooth muscle/collagen content and endothelium content in the corpora cavernosum. LipidTOX™ staining was used to evaluate lipid accumulation. EdU, as a marker of cell activation, and phosphorylated histone 3 (H3P), as a marker of cell mitosis, were also assessed.
Results
The ICP/MAP indicated that erectile function was severely impaired in the ZF group as compared with the ZL group. In the ZF + SW group, erectile function was significantly improved (P < 0.05). Muscle atrophy was seen in the ZF group, while Li‐ESWT increased the muscle content in ZF + SW group. Moreover, the penile endothelium was damaged in the ZF group, and Li‐ESWT enhanced the regeneration of endothelial cells (P < 0.01) in the ZF + SW group. Lipid accumulation was seen in the penile tissue of ZF rats. Li‐ESWT significantly reduced both the amount and the distribution pattern of LipidTOX, suggesting decreased overall lipid infiltration. Furthermore, Li‐ESWT increased EdU‐positive cells and markedly enhanced the phosphorylation level of H3P at Ser‐10 in the ZF + SW group. Most H3P‐positive cells were located within smooth muscle cells, with some located in the endothelium suggesting that these tissues are the reservoirs of penile stem/progenitor cells.
Conclusion
ZF rats can serve as an animal model in which to study OAED. This study reveals that obesity impairs erectile function by causing smooth muscle atrophy, endothelial dysfunction, and lipid accumulation in the corpus cavernosum. Li‐ESWT restored penile haemod |
| doi_str_mv | 10.1111/bju.14202 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2018031142</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2053434114</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3882-60f40dd61d749b1c7ef644b7024deef0f39a83f92161041d57b7d980fc6d92233</originalsourceid><addsrcrecordid>eNp1kbtOwzAUhi0E4lIYeAFkiQWGgm91khEqrkJiaSW2yLGP1ZQ0LnZCm41H4Bl5EgwtDEh48ZH1-dPR_yN0SMkZjee8mLZnVDDCNtAuFVL0BSVPmz8zyeQO2gthSkh8kINttMOyQcIpkbtoOZoABmtBN9hZXLnFx9t7WTdQh7LpMCwbr7Tzc-dBVThMnH5eqFfAzQS8mne4rLGqsSvgC49fVQhOl6oBg8FHaVkBNl2wbR1nV2OvGjxzBqp9tGVVFeBgfffQ-PpqNLztPzze3A0vHvqapynrS2IFMUZSk4isoDoBK4UoEsKEAbDE8kyl3GaMSkoENYOkSEyWEqulyRjjvIdOVt65dy8thCaflUFDVakaXBtyRmhKOI3xRfT4Dzp1ra_jdpEacMFFxCJ1uqK0dyF4sPnclzPlu5yS_KuOPNaRf9cR2aO1sS1mYH7Jn_wjcL4CFjGo7n9Tfnk_Xik_AQ1jlzo</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2053434114</pqid></control><display><type>article</type><title>The effect of low‐intensity extracorporeal shockwave therapy in an obesity‐associated erectile dysfunction rat model</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Ruan, Yajun ; Zhou, Jun ; Kang, Ning ; Reed‐Maldonado, Amanda B. ; Tamaddon, Arianna ; Wang, Bohan ; Wang, Hsun Shuan ; Wang, Guifang ; Banie, Lia ; Lin, Guiting ; Liu, Jihong ; Lue, Tom F.</creator><creatorcontrib>Ruan, Yajun ; Zhou, Jun ; Kang, Ning ; Reed‐Maldonado, Amanda B. ; Tamaddon, Arianna ; Wang, Bohan ; Wang, Hsun Shuan ; Wang, Guifang ; Banie, Lia ; Lin, Guiting ; Liu, Jihong ; Lue, Tom F.</creatorcontrib><description>Objectives
To investigate the feasibility of the Zucker fatty (ZF) rat as a model for research in to obesity‐associated erectile dysfunction (OAED) and to determine the effect of low‐intensity extracorporeal shockwave therapy (Li‐ESWT) on penile tissue and function in these rats.
Materials and methods
Eight new‐born male Zucker lean (ZL group) rats (ZUC‐Leprfa 186) and 16 new‐born male ZF rats (ZUC‐Leprfa 185) were injected with 5‐ethynyl‐2’‐deoxyuridine (EdU) at birth to identify and monitor endogenous stem cells. Insulin tolerance testing was performed at 10 weeks of age. Beginning at 12 weeks of age, eight ZF rats were kept as controls, and the remaining eight ZF rats were treated with Li‐ESWT (0.02 mJ/mm2, 3 Hz, 500 pulses; ZF + SW group) twice a week for 4 weeks. Following a 1‐week washout period, erectile function was evaluated by measuring intracavernosal pressure (ICP) and mean arterial pressure (MAP). Penile tissues were then harvested for histological study to assess smooth muscle/collagen content and endothelium content in the corpora cavernosum. LipidTOX™ staining was used to evaluate lipid accumulation. EdU, as a marker of cell activation, and phosphorylated histone 3 (H3P), as a marker of cell mitosis, were also assessed.
Results
The ICP/MAP indicated that erectile function was severely impaired in the ZF group as compared with the ZL group. In the ZF + SW group, erectile function was significantly improved (P < 0.05). Muscle atrophy was seen in the ZF group, while Li‐ESWT increased the muscle content in ZF + SW group. Moreover, the penile endothelium was damaged in the ZF group, and Li‐ESWT enhanced the regeneration of endothelial cells (P < 0.01) in the ZF + SW group. Lipid accumulation was seen in the penile tissue of ZF rats. Li‐ESWT significantly reduced both the amount and the distribution pattern of LipidTOX, suggesting decreased overall lipid infiltration. Furthermore, Li‐ESWT increased EdU‐positive cells and markedly enhanced the phosphorylation level of H3P at Ser‐10 in the ZF + SW group. Most H3P‐positive cells were located within smooth muscle cells, with some located in the endothelium suggesting that these tissues are the reservoirs of penile stem/progenitor cells.
Conclusion
ZF rats can serve as an animal model in which to study OAED. This study reveals that obesity impairs erectile function by causing smooth muscle atrophy, endothelial dysfunction, and lipid accumulation in the corpus cavernosum. Li‐ESWT restored penile haemodynamic parameters in the ZF rats by restoring smooth muscle and endothelium content and reducing lipid accumulation. The underlying mechanism of Li‐ESWT appears to be activation of stem/progenitor cells, which prompts cellular proliferation and accelerates penile tissue regeneration. Our findings are of interest, not just as a validation of this emerging treatment for erectile dysfunction, but also as a novel and potentially significant method to modulate endogenous stem/progenitor cells in other disease processes.</description><identifier>ISSN: 1464-4096</identifier><identifier>EISSN: 1464-410X</identifier><identifier>DOI: 10.1111/bju.14202</identifier><identifier>PMID: 29573106</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Andrology ; Animals ; Atrophy ; Blood Glucose - metabolism ; Blood pressure ; Cell activation ; Cell proliferation ; Cell Proliferation - physiology ; Collagen ; Collagen - physiology ; Disease Models, Animal ; endogenous stem cells ; Endothelial cells ; Endothelium ; Endothelium, Vascular - physiology ; Erectile dysfunction ; Erectile Dysfunction - blood ; Erectile Dysfunction - etiology ; Erectile Dysfunction - therapy ; ErectileDysfunction ; Extracorporeal Shockwave Therapy - methods ; histone 3 ; Hypoglycemic Agents - pharmacology ; Insulin ; Insulin - pharmacology ; Lipid Metabolism - physiology ; Lipids ; Li‐ESWT ; Male ; Mitosis ; Muscle, Smooth, Vascular - physiology ; Obesity ; Obesity - complications ; obesity‐associated erectile dysfunction ; Penis ; Penis - physiology ; Phosphorylation ; Progenitor cells ; Rats, Zucker ; Rodents ; Smooth muscle ; Stem cell transplantation ; Stem cells ; Stem Cells - physiology ; Zucker Fatty rats</subject><ispartof>BJU international, 2018-07, Vol.122 (1), p.133-142</ispartof><rights>2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd</rights><rights>2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.</rights><rights>BJUI © 2018 BJU International</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3882-60f40dd61d749b1c7ef644b7024deef0f39a83f92161041d57b7d980fc6d92233</citedby><cites>FETCH-LOGICAL-c3882-60f40dd61d749b1c7ef644b7024deef0f39a83f92161041d57b7d980fc6d92233</cites><orcidid>0000-0001-7518-0788 ; 0000-0001-7767-7309 ; 0000-0003-3561-9367 ; 0000-0003-1063-9089</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fbju.14202$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fbju.14202$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29573106$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ruan, Yajun</creatorcontrib><creatorcontrib>Zhou, Jun</creatorcontrib><creatorcontrib>Kang, Ning</creatorcontrib><creatorcontrib>Reed‐Maldonado, Amanda B.</creatorcontrib><creatorcontrib>Tamaddon, Arianna</creatorcontrib><creatorcontrib>Wang, Bohan</creatorcontrib><creatorcontrib>Wang, Hsun Shuan</creatorcontrib><creatorcontrib>Wang, Guifang</creatorcontrib><creatorcontrib>Banie, Lia</creatorcontrib><creatorcontrib>Lin, Guiting</creatorcontrib><creatorcontrib>Liu, Jihong</creatorcontrib><creatorcontrib>Lue, Tom F.</creatorcontrib><title>The effect of low‐intensity extracorporeal shockwave therapy in an obesity‐associated erectile dysfunction rat model</title><title>BJU international</title><addtitle>BJU Int</addtitle><description>Objectives
To investigate the feasibility of the Zucker fatty (ZF) rat as a model for research in to obesity‐associated erectile dysfunction (OAED) and to determine the effect of low‐intensity extracorporeal shockwave therapy (Li‐ESWT) on penile tissue and function in these rats.
Materials and methods
Eight new‐born male Zucker lean (ZL group) rats (ZUC‐Leprfa 186) and 16 new‐born male ZF rats (ZUC‐Leprfa 185) were injected with 5‐ethynyl‐2’‐deoxyuridine (EdU) at birth to identify and monitor endogenous stem cells. Insulin tolerance testing was performed at 10 weeks of age. Beginning at 12 weeks of age, eight ZF rats were kept as controls, and the remaining eight ZF rats were treated with Li‐ESWT (0.02 mJ/mm2, 3 Hz, 500 pulses; ZF + SW group) twice a week for 4 weeks. Following a 1‐week washout period, erectile function was evaluated by measuring intracavernosal pressure (ICP) and mean arterial pressure (MAP). Penile tissues were then harvested for histological study to assess smooth muscle/collagen content and endothelium content in the corpora cavernosum. LipidTOX™ staining was used to evaluate lipid accumulation. EdU, as a marker of cell activation, and phosphorylated histone 3 (H3P), as a marker of cell mitosis, were also assessed.
Results
The ICP/MAP indicated that erectile function was severely impaired in the ZF group as compared with the ZL group. In the ZF + SW group, erectile function was significantly improved (P < 0.05). Muscle atrophy was seen in the ZF group, while Li‐ESWT increased the muscle content in ZF + SW group. Moreover, the penile endothelium was damaged in the ZF group, and Li‐ESWT enhanced the regeneration of endothelial cells (P < 0.01) in the ZF + SW group. Lipid accumulation was seen in the penile tissue of ZF rats. Li‐ESWT significantly reduced both the amount and the distribution pattern of LipidTOX, suggesting decreased overall lipid infiltration. Furthermore, Li‐ESWT increased EdU‐positive cells and markedly enhanced the phosphorylation level of H3P at Ser‐10 in the ZF + SW group. Most H3P‐positive cells were located within smooth muscle cells, with some located in the endothelium suggesting that these tissues are the reservoirs of penile stem/progenitor cells.
Conclusion
ZF rats can serve as an animal model in which to study OAED. This study reveals that obesity impairs erectile function by causing smooth muscle atrophy, endothelial dysfunction, and lipid accumulation in the corpus cavernosum. Li‐ESWT restored penile haemodynamic parameters in the ZF rats by restoring smooth muscle and endothelium content and reducing lipid accumulation. The underlying mechanism of Li‐ESWT appears to be activation of stem/progenitor cells, which prompts cellular proliferation and accelerates penile tissue regeneration. Our findings are of interest, not just as a validation of this emerging treatment for erectile dysfunction, but also as a novel and potentially significant method to modulate endogenous stem/progenitor cells in other disease processes.</description><subject>Andrology</subject><subject>Animals</subject><subject>Atrophy</subject><subject>Blood Glucose - metabolism</subject><subject>Blood pressure</subject><subject>Cell activation</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - physiology</subject><subject>Collagen</subject><subject>Collagen - physiology</subject><subject>Disease Models, Animal</subject><subject>endogenous stem cells</subject><subject>Endothelial cells</subject><subject>Endothelium</subject><subject>Endothelium, Vascular - physiology</subject><subject>Erectile dysfunction</subject><subject>Erectile Dysfunction - blood</subject><subject>Erectile Dysfunction - etiology</subject><subject>Erectile Dysfunction - therapy</subject><subject>ErectileDysfunction</subject><subject>Extracorporeal Shockwave Therapy - methods</subject><subject>histone 3</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Insulin</subject><subject>Insulin - pharmacology</subject><subject>Lipid Metabolism - physiology</subject><subject>Lipids</subject><subject>Li‐ESWT</subject><subject>Male</subject><subject>Mitosis</subject><subject>Muscle, Smooth, Vascular - physiology</subject><subject>Obesity</subject><subject>Obesity - complications</subject><subject>obesity‐associated erectile dysfunction</subject><subject>Penis</subject><subject>Penis - physiology</subject><subject>Phosphorylation</subject><subject>Progenitor cells</subject><subject>Rats, Zucker</subject><subject>Rodents</subject><subject>Smooth muscle</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Stem Cells - physiology</subject><subject>Zucker Fatty rats</subject><issn>1464-4096</issn><issn>1464-410X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kbtOwzAUhi0E4lIYeAFkiQWGgm91khEqrkJiaSW2yLGP1ZQ0LnZCm41H4Bl5EgwtDEh48ZH1-dPR_yN0SMkZjee8mLZnVDDCNtAuFVL0BSVPmz8zyeQO2gthSkh8kINttMOyQcIpkbtoOZoABmtBN9hZXLnFx9t7WTdQh7LpMCwbr7Tzc-dBVThMnH5eqFfAzQS8mne4rLGqsSvgC49fVQhOl6oBg8FHaVkBNl2wbR1nV2OvGjxzBqp9tGVVFeBgfffQ-PpqNLztPzze3A0vHvqapynrS2IFMUZSk4isoDoBK4UoEsKEAbDE8kyl3GaMSkoENYOkSEyWEqulyRjjvIdOVt65dy8thCaflUFDVakaXBtyRmhKOI3xRfT4Dzp1ra_jdpEacMFFxCJ1uqK0dyF4sPnclzPlu5yS_KuOPNaRf9cR2aO1sS1mYH7Jn_wjcL4CFjGo7n9Tfnk_Xik_AQ1jlzo</recordid><startdate>201807</startdate><enddate>201807</enddate><creator>Ruan, Yajun</creator><creator>Zhou, Jun</creator><creator>Kang, Ning</creator><creator>Reed‐Maldonado, Amanda B.</creator><creator>Tamaddon, Arianna</creator><creator>Wang, Bohan</creator><creator>Wang, Hsun Shuan</creator><creator>Wang, Guifang</creator><creator>Banie, Lia</creator><creator>Lin, Guiting</creator><creator>Liu, Jihong</creator><creator>Lue, Tom F.</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7518-0788</orcidid><orcidid>https://orcid.org/0000-0001-7767-7309</orcidid><orcidid>https://orcid.org/0000-0003-3561-9367</orcidid><orcidid>https://orcid.org/0000-0003-1063-9089</orcidid></search><sort><creationdate>201807</creationdate><title>The effect of low‐intensity extracorporeal shockwave therapy in an obesity‐associated erectile dysfunction rat model</title><author>Ruan, Yajun ; Zhou, Jun ; Kang, Ning ; Reed‐Maldonado, Amanda B. ; Tamaddon, Arianna ; Wang, Bohan ; Wang, Hsun Shuan ; Wang, Guifang ; Banie, Lia ; Lin, Guiting ; Liu, Jihong ; Lue, Tom F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3882-60f40dd61d749b1c7ef644b7024deef0f39a83f92161041d57b7d980fc6d92233</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Andrology</topic><topic>Animals</topic><topic>Atrophy</topic><topic>Blood Glucose - metabolism</topic><topic>Blood pressure</topic><topic>Cell activation</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - physiology</topic><topic>Collagen</topic><topic>Collagen - physiology</topic><topic>Disease Models, Animal</topic><topic>endogenous stem cells</topic><topic>Endothelial cells</topic><topic>Endothelium</topic><topic>Endothelium, Vascular - physiology</topic><topic>Erectile dysfunction</topic><topic>Erectile Dysfunction - blood</topic><topic>Erectile Dysfunction - etiology</topic><topic>Erectile Dysfunction - therapy</topic><topic>ErectileDysfunction</topic><topic>Extracorporeal Shockwave Therapy - methods</topic><topic>histone 3</topic><topic>Hypoglycemic Agents - pharmacology</topic><topic>Insulin</topic><topic>Insulin - pharmacology</topic><topic>Lipid Metabolism - physiology</topic><topic>Lipids</topic><topic>Li‐ESWT</topic><topic>Male</topic><topic>Mitosis</topic><topic>Muscle, Smooth, Vascular - physiology</topic><topic>Obesity</topic><topic>Obesity - complications</topic><topic>obesity‐associated erectile dysfunction</topic><topic>Penis</topic><topic>Penis - physiology</topic><topic>Phosphorylation</topic><topic>Progenitor cells</topic><topic>Rats, Zucker</topic><topic>Rodents</topic><topic>Smooth muscle</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Stem Cells - physiology</topic><topic>Zucker Fatty rats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ruan, Yajun</creatorcontrib><creatorcontrib>Zhou, Jun</creatorcontrib><creatorcontrib>Kang, Ning</creatorcontrib><creatorcontrib>Reed‐Maldonado, Amanda B.</creatorcontrib><creatorcontrib>Tamaddon, Arianna</creatorcontrib><creatorcontrib>Wang, Bohan</creatorcontrib><creatorcontrib>Wang, Hsun Shuan</creatorcontrib><creatorcontrib>Wang, Guifang</creatorcontrib><creatorcontrib>Banie, Lia</creatorcontrib><creatorcontrib>Lin, Guiting</creatorcontrib><creatorcontrib>Liu, Jihong</creatorcontrib><creatorcontrib>Lue, Tom F.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>BJU international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ruan, Yajun</au><au>Zhou, Jun</au><au>Kang, Ning</au><au>Reed‐Maldonado, Amanda B.</au><au>Tamaddon, Arianna</au><au>Wang, Bohan</au><au>Wang, Hsun Shuan</au><au>Wang, Guifang</au><au>Banie, Lia</au><au>Lin, Guiting</au><au>Liu, Jihong</au><au>Lue, Tom F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The effect of low‐intensity extracorporeal shockwave therapy in an obesity‐associated erectile dysfunction rat model</atitle><jtitle>BJU international</jtitle><addtitle>BJU Int</addtitle><date>2018-07</date><risdate>2018</risdate><volume>122</volume><issue>1</issue><spage>133</spage><epage>142</epage><pages>133-142</pages><issn>1464-4096</issn><eissn>1464-410X</eissn><abstract>Objectives
To investigate the feasibility of the Zucker fatty (ZF) rat as a model for research in to obesity‐associated erectile dysfunction (OAED) and to determine the effect of low‐intensity extracorporeal shockwave therapy (Li‐ESWT) on penile tissue and function in these rats.
Materials and methods
Eight new‐born male Zucker lean (ZL group) rats (ZUC‐Leprfa 186) and 16 new‐born male ZF rats (ZUC‐Leprfa 185) were injected with 5‐ethynyl‐2’‐deoxyuridine (EdU) at birth to identify and monitor endogenous stem cells. Insulin tolerance testing was performed at 10 weeks of age. Beginning at 12 weeks of age, eight ZF rats were kept as controls, and the remaining eight ZF rats were treated with Li‐ESWT (0.02 mJ/mm2, 3 Hz, 500 pulses; ZF + SW group) twice a week for 4 weeks. Following a 1‐week washout period, erectile function was evaluated by measuring intracavernosal pressure (ICP) and mean arterial pressure (MAP). Penile tissues were then harvested for histological study to assess smooth muscle/collagen content and endothelium content in the corpora cavernosum. LipidTOX™ staining was used to evaluate lipid accumulation. EdU, as a marker of cell activation, and phosphorylated histone 3 (H3P), as a marker of cell mitosis, were also assessed.
Results
The ICP/MAP indicated that erectile function was severely impaired in the ZF group as compared with the ZL group. In the ZF + SW group, erectile function was significantly improved (P < 0.05). Muscle atrophy was seen in the ZF group, while Li‐ESWT increased the muscle content in ZF + SW group. Moreover, the penile endothelium was damaged in the ZF group, and Li‐ESWT enhanced the regeneration of endothelial cells (P < 0.01) in the ZF + SW group. Lipid accumulation was seen in the penile tissue of ZF rats. Li‐ESWT significantly reduced both the amount and the distribution pattern of LipidTOX, suggesting decreased overall lipid infiltration. Furthermore, Li‐ESWT increased EdU‐positive cells and markedly enhanced the phosphorylation level of H3P at Ser‐10 in the ZF + SW group. Most H3P‐positive cells were located within smooth muscle cells, with some located in the endothelium suggesting that these tissues are the reservoirs of penile stem/progenitor cells.
Conclusion
ZF rats can serve as an animal model in which to study OAED. This study reveals that obesity impairs erectile function by causing smooth muscle atrophy, endothelial dysfunction, and lipid accumulation in the corpus cavernosum. Li‐ESWT restored penile haemodynamic parameters in the ZF rats by restoring smooth muscle and endothelium content and reducing lipid accumulation. The underlying mechanism of Li‐ESWT appears to be activation of stem/progenitor cells, which prompts cellular proliferation and accelerates penile tissue regeneration. Our findings are of interest, not just as a validation of this emerging treatment for erectile dysfunction, but also as a novel and potentially significant method to modulate endogenous stem/progenitor cells in other disease processes.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>29573106</pmid><doi>10.1111/bju.14202</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-7518-0788</orcidid><orcidid>https://orcid.org/0000-0001-7767-7309</orcidid><orcidid>https://orcid.org/0000-0003-3561-9367</orcidid><orcidid>https://orcid.org/0000-0003-1063-9089</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1464-4096 |
| ispartof | BJU international, 2018-07, Vol.122 (1), p.133-142 |
| issn | 1464-4096 1464-410X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2018031142 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Andrology Animals Atrophy Blood Glucose - metabolism Blood pressure Cell activation Cell proliferation Cell Proliferation - physiology Collagen Collagen - physiology Disease Models, Animal endogenous stem cells Endothelial cells Endothelium Endothelium, Vascular - physiology Erectile dysfunction Erectile Dysfunction - blood Erectile Dysfunction - etiology Erectile Dysfunction - therapy ErectileDysfunction Extracorporeal Shockwave Therapy - methods histone 3 Hypoglycemic Agents - pharmacology Insulin Insulin - pharmacology Lipid Metabolism - physiology Lipids Li‐ESWT Male Mitosis Muscle, Smooth, Vascular - physiology Obesity Obesity - complications obesity‐associated erectile dysfunction Penis Penis - physiology Phosphorylation Progenitor cells Rats, Zucker Rodents Smooth muscle Stem cell transplantation Stem cells Stem Cells - physiology Zucker Fatty rats |
| title | The effect of low‐intensity extracorporeal shockwave therapy in an obesity‐associated erectile dysfunction rat model |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-29T00%3A53%3A33IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20effect%20of%20low%E2%80%90intensity%20extracorporeal%20shockwave%20therapy%20in%20an%20obesity%E2%80%90associated%20erectile%20dysfunction%20rat%20model&rft.jtitle=BJU%20international&rft.au=Ruan,%20Yajun&rft.date=2018-07&rft.volume=122&rft.issue=1&rft.spage=133&rft.epage=142&rft.pages=133-142&rft.issn=1464-4096&rft.eissn=1464-410X&rft_id=info:doi/10.1111/bju.14202&rft_dat=%3Cproquest_cross%3E2053434114%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2053434114&rft_id=info:pmid/29573106&rfr_iscdi=true |