Amelioration of diabetes-induced cavernosal fibrosis by antioxidant and anti-transforming growth factor-β1 therapies in inducible nitric oxide synthase-deficient mice.
Amelioration of diabetes-induced cavernosal fibrosis by antioxidant and anti-transforming growth factor-β1 therapies in inducible nitric oxide synthase-deficient mice.
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DOI：
10.1111/j.1464-410x.2011.10397.x
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发表时间：
2012-02
影响因子：
4.5
通讯作者：
Gonzalez-Cadavid NF
中科院分区：
文献类型：
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作者：
Ferrini MG;Moon J;Rivera S;Rajfer J;Gonzalez-Cadavid NF
研究糖尿病诱导型一氧化氮合酶敲除（iNOSKo）小鼠与别嘌呤醇（一种抗氧化剂抑制黄嘌呤氧化还原酶）、decorin（一种转化生长因子-β1 （tgf -β1）结合拮抗剂）和莫西多明（一种长寿命一氧化氮供体）是否持续长期单独治疗，以防止糖尿病诱导的海绵体纤维化过程。将iNOSKo小鼠分组治疗，观察其血液化学和组织病理学变化。用别嘌呤醇或decorin治疗8周，可抵消平滑肌细胞减少、体组织细胞凋亡和局部氧化应激增加的影响。Decorin而不是别嘌呤醇增加了平滑肌细胞/胶原蛋白比率，而别嘌呤醇而不是Decorin抑制了全身氧化应激。莫西多明可有效减少局部和全身氧化应激，但不能预防身体纤维化。别嘌呤醇和装饰素都是很有前途的方法，无论是单独使用还是联合使用，都可以保护糖尿病体免受细胞凋亡和纤维化的影响，尽管它们的功能作用仍有待明确。
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-β1 (TGFβ1) -binding antagonist, and molsidomine, a long-life nitric oxide donor, prevent the processes of diabetes-induced cavernosal fibrosis. iNOSKo mice were divided into groups and treated Blood chemistry and histopathology were investigated. 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. 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.