{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T20:48:27Z","timestamp":1779396507639,"version":"3.53.1"},"reference-count":61,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,2,3]],"date-time":"2020-02-03T00:00:00Z","timestamp":1580688000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007055","name":"Third Military Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Diabetes mellitus\u2010induced erectile dysfunction is a common diabetic complication, and new therapeutics and the pathogenesis of diabetes mellitus\u2010induced erectile dysfunction need to be investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The aim was to investigate the pathogenesis of diabetes mellitus\u2010induced erectile dysfunction and the pharmacological mechanism of simvastatin treatment in diabetes mellitus\u2010induced erectile dysfunction model rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>A total of 86 male Sprague Dawley rats aged 8\u00a0weeks old were used in this study. The rats were divided into three groups: control (normal), diabetes mellitus\u2010induced erectile dysfunction (streptozotocin\u2010injected), and diabetes mellitus\u2010induced erectile dysfunction\u00a0+\u00a0simvastatin (sim). Each group was subdivided into two subgroups for in vitro and in vivo analyses. A bioinformatics method was used to detect differences in gene expression in the corpus cavernosum between normal and diabetes mellitus\u2010induced erectile dysfunction rats. Erectile function was measured by a cavernous nerve electrostimulation test. Corpus cavernosum fibrosis was assessed by Masson staining and Western blotting. Immunofluorescence and Western blotting were performed to explore the differential expression of autophagy\u2010related genes and the AMPK\u2010SKP2\u2010CARM1 pathway genes in rat cavernous smooth muscle cells and the corpus cavernosum. The autophagosomes of the corpus cavernosum tissue were observed by transmission electron microscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Autophagy\u2010related genes and pathways (the AMPK and FoxO pathway) were identified by bioinformatics analysis and confirmed at the protein level. Simvastatin, an AMPK agonist, was used to treat diabetes mellitus\u2010induced erectile dysfunction rats for 8\u00a0weeks, demonstrating that erectile function was improved for 80.5% (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05) of rats. Corpus cavernosum fibrosis was alleviated (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05), and autophagy was further enhanced (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05); these results might be partially caused by AMPK\u2010SKP2\u2010CARM1 pathway activation (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion and conclusion<\/jats:title><jats:p>Simvastatin could enhance protective autophagy by activating the AMPK\u2010SKP2\u2010CARM1 pathway to improve erectile function in diabetes mellitus\u2010induced erectile dysfunction rats.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.12758","type":"journal-article","created":{"date-parts":[[2020,1,19]],"date-time":"2020-01-19T05:11:21Z","timestamp":1579410681000},"page":"780-792","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Simvastatin alleviated diabetes mellitus\u2010induced erectile dysfunction in rats by enhancing AMPK pathway\u2010induced autophagy"],"prefix":"10.1111","volume":"8","author":[{"given":"Fan","family":"Ding","sequence":"first","affiliation":[{"name":"Institute of Urinary Surgery Southwest Hospital Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changyu","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunling","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhansong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Urinary Surgery Southwest Hospital Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Zheng","sequence":"additional","affiliation":[{"name":"Institute of Urinary Surgery Southwest Hospital Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhao","family":"Shen","sequence":"additional","affiliation":[{"name":"Institute of Urinary Surgery Southwest Hospital Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Dai","sequence":"additional","affiliation":[{"name":"Institute of Urinary Surgery Southwest Hospital Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0939-028X","authenticated-orcid":false,"given":"Xiaojun","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Urinary Surgery Southwest Hospital Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,2,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000014928"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2010.165"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743-6109.2008.01168.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60520-0"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jsm.12318"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5497.1717"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.09.048"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.10.026"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11255-018-1989-4"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2018.06.004"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsxm.2018.07.013"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/1302672"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/aja.2010.44"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20120546"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.05.023"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1728-5"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature18014"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-9018"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.472"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-015-0054-3"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)38543-9"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky955"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-018-1810-2"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12483"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsxm.2018.12.018"},{"key":"e_1_2_8_29_1","first-page":"e56807","article-title":"Cavernous nerve stimulation and recording of intracavernous pressure in a rat","author":"Hox M","year":"2018","journal-title":"J Vis Exp"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0272.2008.00904.x"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/ijir.2012.36"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743-6109.2011.02603.x"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfu011"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.111.181784"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13444"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.23015"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0929-6646(08)60189-8"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11255-015-1011-3"},{"issue":"743","key":"e_1_2_8_39_1","first-page":"e9","article-title":"Long\u2010term oral administration of 5alpha\u2010reductase inhibitor attenuates erectile function by inhibiting autophagy and promoting apoptosis of smooth muscle cells in corpus cavernosum of aged rats","volume":"82","author":"Zhang MG","year":"2013","journal-title":"Urology"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.03.053"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1159\/000491622"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0172751"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2490-14-24"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2016.01.014"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2925"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0105-6263.2003.00447.x"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2016.02.004"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2016.1144005"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0040-5"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1177\/1753466619890538"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-52627-2"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12512"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.8.1.16645"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.026"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.09.030"},{"key":"e_1_2_8_56_1","first-page":"203","article-title":"Statin decreases helicobacter pylori burden in macrophages by promoting autophagy","volume":"6","author":"Liao WC","year":"2016","journal-title":"Front Cell Infect Microbiol"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/resp.12926"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.28042"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.04.002"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13570"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-018-0856-3"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11895"}],"container-title":["Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.12758","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/andr.12758","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.12758","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T06:42:13Z","timestamp":1693896133000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/andr.12758"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,3]]},"references-count":61,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["10.1111\/andr.12758"],"URL":"https:\/\/doi.org\/10.1111\/andr.12758","archive":["Portico"],"relation":{},"ISSN":["2047-2919","2047-2927"],"issn-type":[{"value":"2047-2919","type":"print"},{"value":"2047-2927","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,3]]},"assertion":[{"value":"2019-08-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}