Sildenafil causes a dose- and time-dependent downregulation of phosphodiesterase type 6 expression in the rat retina.
Sildenafil causes a dose- and time-dependent downregulation of phosphodiesterase type 6 expression in the rat retina.
复制标题
西地那非引起大鼠视网膜中 6 型磷酸二酯酶表达的剂量和时间依赖性下调。
DOI：
10.1038/sj.ijir.3900465
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
McVary,KT
中科院分区：
文献类型：
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作者：
Gonzalez,CM;Bervig,T;Podlasek,C;Huang,CF;McKenna,KE;McVary,KT
目的一些作者提倡每日使用西地那® l预防或治疗勃起功能障碍。然而，尚未发表支持这种给药方案的信息。尚未评估不间断使用sildena® l的安全性，因为它涉及视网膜中PDE 6型的改变。在本研究中，我们调查了短期或长期暴露于各种剂量的sildena® l是否会影响正常光转导cascades.MethodsSustained-release sildena® l pellets中重要酶的表达，将其植入120天龄的雄性大鼠中，浓度为1± 200 mg。在植入后7、14和29天收获大鼠视网膜组织。以GAPDH为内标物，采用定量逆转录聚合酶链反应（RT-PCR）检测PDE 6基因的表达。在植入后14天，高剂量sildena® l最先观察到PDE 6型表达的显著下调（P<< 0.02）。对于所有颗粒制剂，在植入后29天，PDE 6型的表达显著且深度下调！结论Sildena ® l以剂量和时间依赖性方式下调PDE 6型表达。这些结果支持以下解释：PDE 6型抑制导致服用西地那® l的男性中视觉障碍的剂量依赖性临床效应。目前尚不清楚男性长期每日使用西地那® l的影响。
ObjectivesSome authors have advocated the daily use of sildena® l for prophylaxis against, or treatment of, erectile dysfunction. However, no information has been published to support such a dosage regimen. The safety pro® le of uninterrupted use of sildena® l has not been evaluated as it pertains to alteration of PDE type 6 in the retina. In the present study we investigated whether short-or long-term exposure to a variety of sildena® l doses affect the expression of an enzyme important in the normal phototransduction cascade.MethodsSustained-release sildena® l pellets were implanted in 120-day-old male rats with concentrations from 1±200mg. Rat retinal tissue was harvested 7, 14, and 29 days after implantation. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) using GAPDH as an endogenous internal standard was used to quantitate PDE type 6 gene expression.ResultsExpression of PDE type 6 was upregulated after 7 days with dosages 5mg (P<< 0.02). Signi® cant downregulation of PDE type 6 expression was® rst noted with high dose sildena® l 14 days after implantation (P<< 0.02). Expression of PDE type 6 was signi® cantly and profoundly downregulated 29 days after implantation for all pellet formulations!! 10 mg (P<< 0.01).ConclusionsSildena® l downregulates PDE type 6 expression in a dose-and time-dependent fashion. These® ndings support the explanation that PDE type 6 inhibition causes the dosedependent clinical effects of visual disturbance in men taking sildena® l. Implications for longterm, daily use of sildena® l in men are not clear.