{"title":"Icariin inhibits hyperglycemia-induced cell death in penile cavernous tissue and improves erectile function in type 1 diabetic rats.","authors":"Haowei Yang, Wenju Xiong, Jun Jiang, Rui Jiang","doi":"10.1093/sexmed/qfaf017","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Hyperglycemia can cause endothelial cell (EC) and smooth muscle cell (SMC) death in the penile cavernous tissue of rats and lead to erectile dysfunction (ED).</p><p><strong>Objectives: </strong>To investigate the proportions of apoptotic, pyroptotic, and ferroptotic cells among ECs and SMCs in the penile cavernous tissue of type 1 diabetic (T1DM) rats and the mechanism by which icariin (ICA) improves the erectile function of T1DM rats.</p><p><strong>Methods: </strong>A total of 24 9-week-old Sprague-Dawley (SD) rats were randomly divided into 4 groups (<i>n</i> = 6): control group, control + ICA group, diabetic mellitus (DM) group, and DM + ICA group. T1DM rats were generated via the intraperitoneal injection of STZ (45 mg/kg). After 8 weeks, the rats in the control + ICA group and the DM + ICA group were administered ICA (10 mg/kg/d) by gavage for 4 weeks. ROS, MDA, SOD, GSH, SM/C, and NO levels, and GPX4, ACSL4, caspase-1, GSDMD, caspase-3, CD31, α-SMA, and p-eNOS/eNOS expression in penile cavernous tissue and the ICPmax/MAP of 21-week-old rats were detected.</p><p><strong>Results: </strong>The percentage of pyroptotic SMCs in penile cavernosum was no statistically significant difference among these groups. Vs control group, the percentages of apoptotic (20.70% ± 1.60%), pyroptotic (21.02% ± 1.97%), and ferroptotic (9.01% ± 2.00%) ECs and the percentages of apoptotic (15.47% ± 1.36%) and ferroptotic (26.33% ± 3.11%) SMCs in the penile cavernous tissue of the DM group were significantly greater. Vs DM group, the percentages of apoptotic (9.13% ± 1.28%), pyroptotic (13.22 ± 1.26%), and ferroptotic (4.01% ± 0.86%) ECs and the percentages of apoptotic (11.60% ± 1.91%) and ferroptotic (12.71% ± 2.92%) SMCs of the DM + ICA group were significantly lower. Vs the DM group, the levels of caspase-1, GSDMD, ACSL4, and ROS were significantly lower in the penile cavernous tissue of the DM + ICA group. Meanwhile, the levels of GPX4 and maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP) were significantly higher.</p><p><strong>Clinical implications: </strong>The combined inhibition of apoptosis, pyroptosis, and ferroptosis in penile cavernous tissue by ICA provides a theoretical basis for the clinical development of multi-target drugs for the treatment of type 1 diabetes-induced ED.</p><p><strong>Strengths and limitations: </strong>Further experiments are required to clarify whether other types of cell death are involved in the loss of ECs and SMCs in the penile cavernous tissue of T1DM rats.</p><p><strong>Conclusion: </strong>Inhibiting oxidative stress and thereby inhibiting apoptosis, pyroptosis, and ferroptosis in ECs and SMCs of penile cavernous tissue constitute one of the mechanisms through which ICA improves erectile function in T1DM rats.</p>","PeriodicalId":21782,"journal":{"name":"Sexual Medicine","volume":"13 1","pages":"qfaf017"},"PeriodicalIF":2.6000,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950537/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Sexual Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/sexmed/qfaf017","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Hyperglycemia can cause endothelial cell (EC) and smooth muscle cell (SMC) death in the penile cavernous tissue of rats and lead to erectile dysfunction (ED).
Objectives: To investigate the proportions of apoptotic, pyroptotic, and ferroptotic cells among ECs and SMCs in the penile cavernous tissue of type 1 diabetic (T1DM) rats and the mechanism by which icariin (ICA) improves the erectile function of T1DM rats.
Methods: A total of 24 9-week-old Sprague-Dawley (SD) rats were randomly divided into 4 groups (n = 6): control group, control + ICA group, diabetic mellitus (DM) group, and DM + ICA group. T1DM rats were generated via the intraperitoneal injection of STZ (45 mg/kg). After 8 weeks, the rats in the control + ICA group and the DM + ICA group were administered ICA (10 mg/kg/d) by gavage for 4 weeks. ROS, MDA, SOD, GSH, SM/C, and NO levels, and GPX4, ACSL4, caspase-1, GSDMD, caspase-3, CD31, α-SMA, and p-eNOS/eNOS expression in penile cavernous tissue and the ICPmax/MAP of 21-week-old rats were detected.
Results: The percentage of pyroptotic SMCs in penile cavernosum was no statistically significant difference among these groups. Vs control group, the percentages of apoptotic (20.70% ± 1.60%), pyroptotic (21.02% ± 1.97%), and ferroptotic (9.01% ± 2.00%) ECs and the percentages of apoptotic (15.47% ± 1.36%) and ferroptotic (26.33% ± 3.11%) SMCs in the penile cavernous tissue of the DM group were significantly greater. Vs DM group, the percentages of apoptotic (9.13% ± 1.28%), pyroptotic (13.22 ± 1.26%), and ferroptotic (4.01% ± 0.86%) ECs and the percentages of apoptotic (11.60% ± 1.91%) and ferroptotic (12.71% ± 2.92%) SMCs of the DM + ICA group were significantly lower. Vs the DM group, the levels of caspase-1, GSDMD, ACSL4, and ROS were significantly lower in the penile cavernous tissue of the DM + ICA group. Meanwhile, the levels of GPX4 and maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP) were significantly higher.
Clinical implications: The combined inhibition of apoptosis, pyroptosis, and ferroptosis in penile cavernous tissue by ICA provides a theoretical basis for the clinical development of multi-target drugs for the treatment of type 1 diabetes-induced ED.
Strengths and limitations: Further experiments are required to clarify whether other types of cell death are involved in the loss of ECs and SMCs in the penile cavernous tissue of T1DM rats.
Conclusion: Inhibiting oxidative stress and thereby inhibiting apoptosis, pyroptosis, and ferroptosis in ECs and SMCs of penile cavernous tissue constitute one of the mechanisms through which ICA improves erectile function in T1DM rats.
期刊介绍：
Sexual Medicine is an official publication of the International Society for Sexual Medicine, and serves the field as the peer-reviewed, open access journal for rapid dissemination of multidisciplinary clinical and basic research in all areas of global sexual medicine, and particularly acts as a venue for topics of regional or sub-specialty interest. The journal is focused on issues in clinical medicine and epidemiology but also publishes basic science papers with particular relevance to specific populations. Sexual Medicine offers clinicians and researchers a rapid route to publication and the opportunity to publish in a broadly distributed and highly visible global forum. The journal publishes high quality articles from all over the world and actively seeks submissions from countries with expanding sexual medicine communities. Sexual Medicine relies on the same expert panel of editors and reviewers as The Journal of Sexual Medicine and Sexual Medicine Reviews.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
