Spironolactone Protects against Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetic Rats
Spironolactone (SPR) has been shown to protect diabetic cardiomyopathy (DCM), but the specific mechanisms are not fully understood. Here, we determined the cardioprotective role of SPR in diabetic mice and further explored the potential mechanisms in both in vivo and in vitro models. Streptozotocin-...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2018-01-01
|
| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2018/9232065 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832548641162657792 |
|---|---|
| author | Wenjuan Liu Wei Gong Min He Yemei Liu Yeping Yang Meng Wang Meng Wu Shizhe Guo Yifei Yu Xuanchun Wang Fei Sun Yiming Li Linuo Zhou Shengmei Qin Zhaoyun Zhang |
| author_facet | Wenjuan Liu Wei Gong Min He Yemei Liu Yeping Yang Meng Wang Meng Wu Shizhe Guo Yifei Yu Xuanchun Wang Fei Sun Yiming Li Linuo Zhou Shengmei Qin Zhaoyun Zhang |
| author_sort | Wenjuan Liu |
| collection | DOAJ |
| description | Spironolactone (SPR) has been shown to protect diabetic cardiomyopathy (DCM), but the specific mechanisms are not fully understood. Here, we determined the cardioprotective role of SPR in diabetic mice and further explored the potential mechanisms in both in vivo and in vitro models. Streptozotocin- (STZ-) induced diabetic rats were used as the in vivo model. After the onset of diabetes, rats were treated with either SPR (STZ + SPR) or saline (STZ + NS) for 12 weeks; nondiabetic rats were used as controls (NDCs). In vitro, H9C2 cells were exposed to aldosterone, with or without SPR. Cardiac structure was investigated with transmission electron microscopy and pathological examination; immunohistochemistry was performed to detect nitrotyrosine, collagen-1, TGF-β1, TNF-α, and F4/80 expression; and gene expression of markers for oxidative stress, inflammation, fibrosis, and energy metabolism was detected. Our results suggested that SPR attenuated mitochondrial morphological abnormalities and sarcoplasmic reticulum enlargement in diabetic rats. Compared to the STZ + NS group, cardiac oxidative stress, fibrosis, inflammation, and mitochondrial dysfunction were improved by SPR treatment. Our study showed that SPR had cardioprotective effects in diabetic rats by ameliorating mitochondrial dysfunction and reducing fibrosis, oxidative stress, and inflammation. This study, for the first time, indicates that SPR might be a potential treatment for DCM. |
| format | Article |
| id | doaj-art-dbe5ae7315d642538bcc6e0032e07974 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-dbe5ae7315d642538bcc6e0032e079742025-02-03T06:13:36ZengWileyJournal of Diabetes Research2314-67452314-67532018-01-01201810.1155/2018/92320659232065Spironolactone Protects against Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetic RatsWenjuan Liu0Wei Gong1Min He2Yemei Liu3Yeping Yang4Meng Wang5Meng Wu6Shizhe Guo7Yifei Yu8Xuanchun Wang9Fei Sun10Yiming Li11Linuo Zhou12Shengmei Qin13Zhaoyun Zhang14Division of Endocrinology and Metabolism, Huashan Hospital, Fudan University, 12 Wulumuqi Road, Shanghai 200040, ChinaDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, 12 Wulumuqi Road, Shanghai 200040, ChinaDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, 12 Wulumuqi Road, Shanghai 200040, ChinaDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, 12 Wulumuqi Road, Shanghai 200040, ChinaDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, 12 Wulumuqi Road, Shanghai 200040, ChinaDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, 12 Wulumuqi Road, Shanghai 200040, ChinaDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, 12 Wulumuqi Road, Shanghai 200040, ChinaDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, 12 Wulumuqi Road, Shanghai 200040, ChinaDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, 12 Wulumuqi Road, Shanghai 200040, ChinaDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, 12 Wulumuqi Road, Shanghai 200040, ChinaDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, 12 Wulumuqi Road, Shanghai 200040, ChinaDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, 12 Wulumuqi Road, Shanghai 200040, ChinaDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, 12 Wulumuqi Road, Shanghai 200040, ChinaDepartment of Cardiology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, ChinaDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, 12 Wulumuqi Road, Shanghai 200040, ChinaSpironolactone (SPR) has been shown to protect diabetic cardiomyopathy (DCM), but the specific mechanisms are not fully understood. Here, we determined the cardioprotective role of SPR in diabetic mice and further explored the potential mechanisms in both in vivo and in vitro models. Streptozotocin- (STZ-) induced diabetic rats were used as the in vivo model. After the onset of diabetes, rats were treated with either SPR (STZ + SPR) or saline (STZ + NS) for 12 weeks; nondiabetic rats were used as controls (NDCs). In vitro, H9C2 cells were exposed to aldosterone, with or without SPR. Cardiac structure was investigated with transmission electron microscopy and pathological examination; immunohistochemistry was performed to detect nitrotyrosine, collagen-1, TGF-β1, TNF-α, and F4/80 expression; and gene expression of markers for oxidative stress, inflammation, fibrosis, and energy metabolism was detected. Our results suggested that SPR attenuated mitochondrial morphological abnormalities and sarcoplasmic reticulum enlargement in diabetic rats. Compared to the STZ + NS group, cardiac oxidative stress, fibrosis, inflammation, and mitochondrial dysfunction were improved by SPR treatment. Our study showed that SPR had cardioprotective effects in diabetic rats by ameliorating mitochondrial dysfunction and reducing fibrosis, oxidative stress, and inflammation. This study, for the first time, indicates that SPR might be a potential treatment for DCM.http://dx.doi.org/10.1155/2018/9232065 |
| spellingShingle | Wenjuan Liu Wei Gong Min He Yemei Liu Yeping Yang Meng Wang Meng Wu Shizhe Guo Yifei Yu Xuanchun Wang Fei Sun Yiming Li Linuo Zhou Shengmei Qin Zhaoyun Zhang Spironolactone Protects against Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetic Rats Journal of Diabetes Research |
| title | Spironolactone Protects against Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetic Rats |
| title_full | Spironolactone Protects against Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetic Rats |
| title_fullStr | Spironolactone Protects against Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetic Rats |
| title_full_unstemmed | Spironolactone Protects against Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetic Rats |
| title_short | Spironolactone Protects against Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetic Rats |
| title_sort | spironolactone protects against diabetic cardiomyopathy in streptozotocin induced diabetic rats |
| url | http://dx.doi.org/10.1155/2018/9232065 |
| work_keys_str_mv | AT wenjuanliu spironolactoneprotectsagainstdiabeticcardiomyopathyinstreptozotocininduceddiabeticrats AT weigong spironolactoneprotectsagainstdiabeticcardiomyopathyinstreptozotocininduceddiabeticrats AT minhe spironolactoneprotectsagainstdiabeticcardiomyopathyinstreptozotocininduceddiabeticrats AT yemeiliu spironolactoneprotectsagainstdiabeticcardiomyopathyinstreptozotocininduceddiabeticrats AT yepingyang spironolactoneprotectsagainstdiabeticcardiomyopathyinstreptozotocininduceddiabeticrats AT mengwang spironolactoneprotectsagainstdiabeticcardiomyopathyinstreptozotocininduceddiabeticrats AT mengwu spironolactoneprotectsagainstdiabeticcardiomyopathyinstreptozotocininduceddiabeticrats AT shizheguo spironolactoneprotectsagainstdiabeticcardiomyopathyinstreptozotocininduceddiabeticrats AT yifeiyu spironolactoneprotectsagainstdiabeticcardiomyopathyinstreptozotocininduceddiabeticrats AT xuanchunwang spironolactoneprotectsagainstdiabeticcardiomyopathyinstreptozotocininduceddiabeticrats AT feisun spironolactoneprotectsagainstdiabeticcardiomyopathyinstreptozotocininduceddiabeticrats AT yimingli spironolactoneprotectsagainstdiabeticcardiomyopathyinstreptozotocininduceddiabeticrats AT linuozhou spironolactoneprotectsagainstdiabeticcardiomyopathyinstreptozotocininduceddiabeticrats AT shengmeiqin spironolactoneprotectsagainstdiabeticcardiomyopathyinstreptozotocininduceddiabeticrats AT zhaoyunzhang spironolactoneprotectsagainstdiabeticcardiomyopathyinstreptozotocininduceddiabeticrats |