Amelioration of diabetes-induced cavernosal fibrosis by antioxidant and anti-transforming growth factor-beta 1 therapies in inducible nitric oxide synthase-deficient mice

作者：Ferrini Monica G^*; Moon Joanne; Rivera Steve; Rajfer Jacob; Gonzalez Cadavid Nestor F

来源：BJU International, 2012, 109(4): 586-593.

DOI：10.1111/j.1464-410X.2011.10397.x

• erectile dysfunction
• smooth muscle
• penis
• collagen
• nitric oxide
• decorin
• allopurinol
• molsidomine
• apoptosis

OBJECTIVE
To investigate whether sustained long-term separate treatments of diabetic inducible nitric oxide synthase knockout (iNOSKo) mice with allopurinol, an antioxidant inhibiting xanthine oxidoreductase, decorin, a transforming growth factor-beta 1 (TGF beta 1) -binding antagonist, and molsidomine, a long-life nitric oxide donor, prevent the processes of diabetes-induced cavernosal fibrosis.
MATERIALS AND METHODS
Eight week old male iNOS knock out (iNOSKo) mice were made diabetic by injecting 150 mg/kg B. W Streptozotocin (1P) with were either left untreated or treated with the oral antioxidant allopurinol (40 mg/kg/day), or decoin (50 mg, 1P, twice), as an anti-TGF beta 1 agent (n = 8/group).
Glycemia and oxidative stress markers were determined in blood and urine.
Paraffin-embedded tissue sections from the penile shaft were subjected to Masson trichrome staining for the smooth muscle (smc)/collagen ratio, and imunostaining for smc content, profibrotic factors, oxidative stress, cell replication and cell death markers followed by quantitative image analysis.
RESULTS
Eight-week treatment with either allopurinol or decorin counteracted the decrease in smooth muscle cells and the increase in apoptosis and local oxidative stress within the corpora tissue.
Decorin but not allopurinol increased the smooth muscle cell/collagen ratio, whereas allopurinol but not decorin inhibited systemic oxidative stress.
Molsidomine was effective in reducing both local and systemic oxidative stress, but did not prevent corporal fibrosis.
CONCLUSION
Both allopurinol and decorin appear as promising approaches either as a single or a combined pharmacological modality for protecting the diabetic corpora from undergoing apoptosis and fibrosis although their functional effects still need to be defined.

• 出版日期2012-2