二甲双胍激活AMPK/mTOR通路上调阴茎海绵体自噬增强老年ED大鼠勃起功能

丁凡; 李宏伟; 欧阳勤; 吴小军

doi:10.16016/j.1000-5404.201912208

您当前的位置：

首页 >

文章列表页 >

二甲双胍激活AMPK/mTOR通路上调阴茎海绵体自噬增强老年ED大鼠勃起功能

基础医学 | 更新时间：2026-01-09

- 二甲双胍激活AMPK/mTOR通路上调阴茎海绵体自噬增强老年ED大鼠勃起功能
- Metformin enhances erectile function in rats with aging-induced erectile dysfunction by activating AMPK/mTOR pathway-regulated autophagy in corpus cavernosum
- 第三军医大学学报 2020年42卷第11期页码：1109-1115
- 作者机构：
- 作者简介：
- 基金信息：
  
  国家自然科学基金面上项目(81270692)
- DOI：10.16016/j.1000-5404.201912208
  中图分类号：
- 收稿：2019-12-21，
  
  纸质出版：2020-06-15
- 稿件说明：
移动端阅览
丁凡, 李宏伟, 欧阳勤, 等. 二甲双胍激活AMPK/mTOR通路上调阴茎海绵体自噬增强老年ED大鼠勃起功能[J]. 第三军医大学学报, 2020,42(11):1109-1115.

Fan DING, Hongwei LI, Qin OUYANG, et al. Metformin enhances erectile function in rats with aging-induced erectile dysfunction by activating AMPK/mTOR pathway-regulated autophagy in corpus cavernosum[J]. Journal of Third Military Medical University, 2020, 42(11): 1109-1115.
丁凡, 李宏伟, 欧阳勤, 等. 二甲双胍激活AMPK/mTOR通路上调阴茎海绵体自噬增强老年ED大鼠勃起功能[J]. 第三军医大学学报, 2020,42(11):1109-1115. DOI： 10.16016/j.1000-5404.201912208.

Fan DING, Hongwei LI, Qin OUYANG, et al. Metformin enhances erectile function in rats with aging-induced erectile dysfunction by activating AMPK/mTOR pathway-regulated autophagy in corpus cavernosum[J]. Journal of Third Military Medical University, 2020, 42(11): 1109-1115. DOI： 10.16016/j.1000-5404.201912208.

摘要

Abstract

Objective

To investigate the effect of metformin on erectile function and its regulation on cavernous fibrosis and autophagy in aged rats

and explore the underlying mechanism.

Methods

Forty healthy 2-month-old male SD rats were randomly divided into groups A

C and D. APO at a dose of 100 mg/kg was injected intraperitoneally to the rats of the former group (at 2 months old) and of the latter 3 group (at 18 months old) to screen the rats with aging-induced erectile dysfunction. Those with ED from the latter 3 groups and those without ED in the group A were employed for the further studies. Group A (control group) was given intragastrical infusion of normal saline for 2 months f

rom the age of 2 months. The rats of the latter 3 groups (18 months old) were injected inragastrically with normal saline

metformin at 300 mg·kg

-1

·d

-1

alone and combined with 0.2 mg/kg compound C for 2 months

respectively. The erectile function was measured by electrical stimulation. The cavernous fibrosis was detected by Masson staining. The autophagy level was detected by Western blotting and transmission electron microscopy. The expression of AMPK/mTOR pathway related proteins was detected by immunofluorescence assay and Western blotting.

Results

Compared with the group A

the group B had significantly decreased erectile function (

0.05)

aggravated cavernous fibrosis

and inhibited autophagy and AMPK/mTOR pathway (

0.05). Metformin treatment slightly restored the erectile function in the group C (

0.05)

alleviated the cavernous fibrosis

upregulated autophagy (

0.05)

and activated the AMPK/mTOR pathway (

0.05). But these indicators still did not reach the levels of the group A (

0.05). There were no significant differences in above indicators between group D and group B.

Conclusion

Metformin alleviates cavernous fibrosis and improves erectile function in aging-induced erectile dysfunction rats

which may be related to the activation of AMPK/mTOR pathway to up-regulate autophagy.

关键词

Keywords

references

KAYA E SIKKA S C KADOWITZ P J Aging and sexual health: getting to the problem Aging Male 2017 20 2 65 80 10.1080/13685538.2017.1295435 KAYA E, SIKKA S C, KADOWITZ P J, et al . Aging and sexual health: getting to the problem[J ] . Aging Male, 2017, 20 (2): 65-80. DOI:10.1080/13685538.2017.1295435.

LEE M SHARIFI R Non-invasive management options for erectile dysfunction when a phosphodiesterase type 5 inhibitor fails Drugs Aging 2018 35 3 175 187 10.1007/s40266-018-0528-4 LEE M, SHARIFI R. Non-invasive management options for erectile dysfunction when a phosphodiesterase type 5 inhibitor fails[J]. Drugs Aging, 2018, 35(3): 175-187. DOI:10.1007/s40266-018-0528-4.

YAFI F A JENKINS L ALBERSEN M Erectile dysfunction Nat Rev Dis 2016 2 16003 10.1038/nrdp.2016.3 YAFI F A, JENKINS L, ALBERSEN M, et al . Erectile dysfun ction[J ] . Nat Rev Dis, 2016, 2: 16003. DOI:10.1038/nrdp.2016.3.

GALLUZZI L GREEN D R Autophagy-independent functions of the autophagy machinery Cell 2019 177 7 1682 1699 10.1016/j.cell.2019.05.026 GALLUZZI L, GREEN D R. Autophagy-independent functions of the autophagy machinery[J]. Cell, 2019, 177(7): 1682-1699. DOI:10.1016/j.cell.2019.05.026.

ZHANG J WU X J ZHUO D X Effect of tankyrase 1 on autophagy in the corpus cavernosum smooth muscle cells from ageing rats with erectile dysfunction and its potential mechanism Asian J Androl 2010 12 5 744 752 10.1038/aja.2010.44 ZHANG J, WU X J, ZHUO D X, et al . Effect of tankyrase 1 on autophagy in the corpus cavernosum smooth muscle cells from ageing rats with erectile dysfunction and its potential mechanism[J ] . Asian J Androl, 2010, 12 (5): 744-752. DOI:10.1038/aja.2010.44.

BARZILAI N CRANDALL J P KRITCHEVSKY S B Metformin as a tool to target aging Cell Metab 2016 23 6 1060 1065 10.1016/j.cmet.2016.05.011 BARZILAI N, CRANDALL J P, KRITCHEVSKY S B, et al . Metformin as a tool to target aging[J ] . Cell Metab, 2016, 23 (6): 1060-1065. DOI:10.1016/j.cmet.2016.05.011.

ZHANG Z ZHANG H Y ZHANG Y Inactivation of the Ras/MAPK/PPARγ signaling Axis alleviates diabetic mellitus-induced erectile dysfunction through suppression of corpus cavernosal endothelial cell apoptosis by inhibiting HMGCS2 expression Endocrine 2019 63 3 615 631 10.1007/s12020-018-1810-2 ZHANG Z, ZHANG H Y, ZHANG Y, et al . Inactivation of the Ras/MAPK/PPARγ signaling Axis alleviates diabetic mellitus-induced erectile dysfunction through suppression of corpus cavernosal endothelial cell apoptosis by inhibiting HMGCS2 expression[J ] . Endocrine, 2019, 63(3): 615-631. DOI:10.1007/s12020-018-1810-2.

SILVA F H ALEXANDRE E C CALMASINI F B Treatment with metformin improves erectile dysfunction in a murine model of obesity associated with insulin resistance Urology 2015 86 2 423.e1 423.e6 10.1016/j.urology.2015.04.035 SILVA F H, ALEXANDRE E C, CALMASINI F B, et al . Treatment with metformin improves erectile dysfunction in a murine model of obesity associated with insulin resistance[J ] . Urology, 2015, 86(2): 423.e1-423.e6. DOI:10.1016/j.urology.2015.04.035.

KIM Y M KIM M Y KIM H J Compound C independent of AMPK inhibits ICAM-1 and VCAM-1 expression in inflammatory stimulants-activated endothelial cells in vitro and in vivo Atherosclerosis 2011 219 1 57 64 10.1016/j.atherosclerosis.2011.06.043 KIM Y M, KIM M Y, KIM H J, et al . Compound C independent of AMPK inhibits ICAM-1 and VCAM-1 expression in inflammatory stimulants-activated endothelial cells in vitro and in vivo[J ] . Atherosclerosis, 2011, 219(1): 57-64. DOI:10.1016/j.atherosclerosis.2011.06.043.

CHEN L STAUBLI S E SCHNEIDER M P Phosphodiesterase 5 inhibitors for the treatment of erectile dysfunction: a trade-off network meta-analysis Eur Urol 2015 68 4 674 680 10.1016/j.eururo.2015.03.031 CHEN L, STAUBLI S E, SCHNEIDER M P, et al . Phosphodiesterase 5 inhibitors for the treatment of erectile dysfunction: a trade-off network meta-analysis[J ] . Eur Urol, 2015, 68 (4): 674-680. DOI:10.1016/j.eururo.2015.03.031.

ESCOBAR K A COLE N H MERMIER C M Autophagy and aging: Maintaining the proteome through exercise and caloric restriction Aging cell 2019 18 1 e12876 10.1111/acel.12876 ESCOBAR K A, COLE N H, MERMIER C M, et al . Autophagy and aging: Maintaining the proteome through exercise and caloric restriction[J ] . Aging cell, 2019, 18(1): e12876. DOI:10.1111/acel.12876.

TANG Z CUI K LUAN Y Human tissue kallikrein 1 ameliorates erectile function via modulation of macroautophagy in aged transgenic rats Andrology 2018 6 5 766 774 10.1111/andr.12512 TANG Z, CUI K, LUAN Y, et al . Human tissue kallikrein 1 ameliorates erectile function via modulation of macroautophagy in aged transgenic rats[J ] . Andrology, 2018, 6(5): 766-774. DOI:10.1111/andr.12512.

REN J ZHANG Y Targeting autophagy in aging and aging-related cardiovascular diseases Trends Pharmacol Sci 2018 39 12 1064 1076 10.1016/j.tips.2018.10.005 REN J, ZHANG Y. Targeting autophagy in aging and aging-related cardiovascular diseases[J]. Trends Pharmacol Sci, 2018, 39 (12): 1064-1076. DOI:10.1016/j.tips.2018.10.005.

PATEL J P LEE E H MENA C I Effects of metformin on endothelial health and erectile dysfunction Transl Androl Urol 2017 6 3 556 565 10.21037/tau.2017.03.52 PATEL J P, LEE E H, MENA C I, et al . Effects of metformin on endothelial health and erectile dysfunction[J ] . Transl Androl Urol, 2017, 6 (3): 556-565. DOI:10.21037/tau.2017.03.52.

RANGARAJAN S BONE N B ZMIJEWSKA A A Metformin reverses established lung fibrosis in a bleomycin model Nat Med 2018 24 8 1121 1127 10.1038/s41591-018-0087-6 RANGARAJAN S, BONE N B, ZMIJEWSKA A A, et al . Metformin reverses established lung fibrosis in a bleomycin model[J ] . Nat Med, 2018, 24 (8): 1121-1127. DOI:10.1038/s41591-018-0087-6.

BAE J H KIM J W KWEON G R Corpus cavernosal smooth muscle relaxation effect of a novel AMPK activator, beta-lapachone J Sex Med 2011 8 8 2205 2214 10.1111/j.1743-6109.2010.01809.x BAE J H, KIM J W, KWEON G R, et al . Corpus cavernosal smooth muscle relaxation effect of a novel AMPK activator, beta-lapachone[J ] . J Sex Med, 2011, 8 (8): 2205-2214. DOI:10.1111/j.1743-6109.2010.01809.x.

ZHU G Q JEON S H BAE W J Efficient promotion of autophagy and angiogenesis using mesenchymal stem cell therapy enhanced by the low-energy shock waves in the treatment of erectile dysfunction Stem cells Int 2018 2018 1302672 10.1155/2018/1302672 ZHU G Q, JEON S H, BAE W J, et al . Efficient promotion of autophagy and angiogenesis using mesenchymal stem cell therapy enhanced by the low-energy shock waves in the treatment of erectile dysfunction[J ] . Stem cells Int, 2018, 2018: 1302672. DOI:10.1155/2018/1302672.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

二甲双胍对血管内皮细胞自噬的作用

新型二甲双胍碳点促进炎症微环境下人牙周膜干细胞成骨分化

RANKL通过ROS介导HIF-1α下调促进自噬和破骨细胞分化

转录因子EB增强巨噬细胞自噬功能及逆转内毒素耐受的作用

自噬诱导剂亚精胺改善脑出血后脑损伤