A2B Adenosine Receptor Agonist Improves Erectile Function in Diabetic Rats.
A2B Adenosine Receptor Agonist Improves Erectile Function in Diabetic Rats.
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A2B 腺苷受体激动剂改善糖尿病大鼠的勃起功能
DOI：
10.1620/tjem.237.141
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Zhang Nan
中科院分区：
文献类型：
--
作者：
Wen Jiaming;Wang Bohan;Du Chuanjun;Xu Gang;Zhang Zhewei;Li Yi;Zhang Nan
糖尿病是勃起功能障碍（艾德）的重要危险因素。最近的研究表明，A2 B腺苷受体（ADORA 2B）信号传导是阴茎勃起所必需的。因此，我们假设糖尿病艾德可能是由于受损的A2 B腺苷信号。为了验证这一假设，我们通过注射链脲佐菌素产生糖尿病大鼠作为动物模型。12周后，采用免疫组化法检测ADORA 2B的表达。采用Western Blot和定量PCR方法测定ADURA 2B的表达水平。阴茎海绵体内压（ICP）测量用于评估勃起功能。在ICP测量前60分钟，糖尿病大鼠接受BAY 60-6583（ADORA 2B激动剂）或溶媒溶液的单次静脉注射。结果显示，ADORA 2B在对照组小鼠阴茎组织的神经束、平滑肌和内皮细胞中均有表达。Western Blot和定量PCR结果显示，糖尿病大鼠阴茎组织中ADORA 2B蛋白和mRNA的表达水平明显降低。功能研究表明，与年龄匹配的对照大鼠相比，糖尿病大鼠由电刺激诱导的勃起反应显著降低。然而，在BAY 60-6583治疗后60分钟，糖尿病大鼠的勃起功能得到改善，表明ADORA 2B信号传导的增强可能改善糖尿病ED的勃起功能。这项临床前研究揭示了BAY 60-6583作为治疗糖尿病ED的有效和基于机制的药物的先前未被认识的治疗可能性。我们认为A2 B腺苷信号通路受损是糖尿病性ED的病理机制之一。
Diabetes is an important risk factor for erectile dysfunction (ED). Recent studies have indicated that A2B adenosine receptor (ADORA2B) signaling is essential for penile erection. Thus, we hypothesize that diabetic ED may be attributed to impaired A2B adenosine signaling. To test this hypothesis, we generated diabetic rats by injecting streptozocin as animal model. After 12 weeks, immunohistochemistry staining was used to localize the expression of ADORA2B. Western Blot and quantitative PCR were employed to determine ADORA2B expression level. Intracavernosal pressure (ICP) measurement was used to evaluate erectile function. Diabetic rats received a single intravenous injection of BAY 60-6583, an ADORA2B agonist, or vehicle solution, at 60 min before the ICP measurement. The results showed that ADORA2B expressed in the nerve bundle, smooth muscle, and endothelium in penile tissue of control mice. Western Blot and quantitative PCR results indicated that the expression levels of ADORA2B protein and mRNA were significantly reduced in penile tissues of diabetic rats. Functional studies showed that the erectile response induced by electrical stimulation was remarkably decreased in diabetic rats, compared with age-matched control rats. However, at 60 min after BAY 60-6583 treatment, the erectile function was improved in diabetic rats, suggesting that enhancement of ADORA2B signaling may improve erectile function in diabetic ED. This preclinical study has revealed a previously unrecognized therapeutic possibility of BAY 60-6583 as an effective and mechanism-based drug to treat diabetic ED. In conclusion, we propose that impaired A2B adenosine signaling is one of the pathological mechanisms of diabetic ED.
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影响因子：
56.9
作者：
BURNETT, AL;LOWENSTEIN, CJ;SNYDER, SH
通讯作者：
SNYDER, SH
影响因子：
6.6
作者：
Burnett, AL
通讯作者：
Burnett, AL
DOI：
10.1097/01.ju.0000152127.87796.9f
发表时间：
2005-03
期刊：
The Journal of urology
影响因子：
--
作者：
A. Seftel
通讯作者：
A. Seftel
影响因子：
1.1
作者：
Giuliano, F.;Droupy, S.
通讯作者：
Droupy, S.
DOI：
10.1007/978-3-642-36172-2_201015
发表时间：
2000
期刊：
The New England journal of medicine
影响因子：
--
作者：
T. Lue
通讯作者：
T. Lue