Metformin enhances erectile function in rats with aging-induced erectile dysfunction by activating AMPK/mTOR pathway-regulated autophagy in corpus cavernosum

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, B, 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 from 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 (P < 0.05), aggravated cavernous fibrosis, and inhibited autophagy and AMPK/mTOR pathway (P < 0.05). Metformin treatment slightly restored the erectile function in the group C (P < 0.05), alleviated the cavernous fibrosis, upregulated autophagy (P < 0.05), and activated the AMPK/mTOR pathway (P < 0.05). But these indicators still did not reach the levels of the group A (P < 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.

Keywords

• erectile dysfunction
• metformin
• autophagy
• ampk
• mtor