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长期给予大鼠内耳西地那非后的组织病理学结果。

Histopathologic results of long-term sildenafil administration on rat inner ear.

机构信息

Department of ENT and Head and Neck Surgery, Dicle University Medical College, Diyarbakir, Turkey.

出版信息

Am J Otolaryngol. 2012 Nov-Dec;33(6):667-72. doi: 10.1016/j.amjoto.2012.04.005. Epub 2012 Jun 8.

DOI:10.1016/j.amjoto.2012.04.005
PMID:22683010
Abstract

OBJECTIVES

Sildenafil, a selective inhibitor of phosphodiesterase type 5, is widely used for the treatment of erectile dysfunction. Although cochlear effects of phosphodiesterase type 5 inhibitors remain still unclear because of inadequate data, some evidence that recently emerged indicates that these medications may be responsible for hearing impairment. In the present study, we aimed to examine the histopathologic effects of long-term sildenafil use on the cochlea in a rat model.

METHODS

The study was performed with adult male Wistar albino rats. The control group was fed on standard laboratory diet. The study group was applied orally with sildenafil therapy, 1.5 mg/kg once a day for 45 days. Rats were anesthetized and decapitated. Each temporal bone was dissected, and the cochleas were removed en bloc. The inner-ear biopsy specimens were examined histologically with hematoxylin and eosin and caspase 3 immunoreaction under light microscopy.

RESULTS

Hematoxylin and eosin staining showed no distinctive difference between the control group and the sildenafil group. With immunohistochemical examination, caspase 3 immunoreactivity was observed in the sildenafil group. In the control group, caspase 3 immunoreactivity was not observed.

CONCLUSIONS

The caspase 3 immunoreactivity in the sildenafil group was strongly associated with an increase in apoptotic events in the cochlea. Long-term use of sildenafil can cause hearing impairment through increased apoptosis.

摘要

目的

西地那非是一种磷酸二酯酶 5 型的选择性抑制剂,被广泛用于治疗勃起功能障碍。尽管由于数据不足,磷酸二酯酶 5 型抑制剂对耳蜗的影响仍不清楚,但最近出现的一些证据表明,这些药物可能导致听力损伤。在本研究中,我们旨在通过大鼠模型研究长期使用西地那非对耳蜗的组织病理学影响。

方法

该研究采用成年雄性 Wistar 白化大鼠进行。对照组给予标准实验室饮食。研究组给予西地那非治疗,每天 1.5mg/kg,连续 45 天。大鼠麻醉后断头。每个颞骨被解剖,整块取出耳蜗。用苏木精和伊红染色和 caspase 3 免疫反应在光镜下对内耳活检标本进行组织学检查。

结果

苏木精和伊红染色显示对照组和西地那非组之间没有明显差异。免疫组织化学检查显示,西地那非组 caspse 3 免疫反应阳性。在对照组中,未观察到 caspse 3 免疫反应。

结论

西地那非组的 caspase 3 免疫反应与耳蜗中凋亡事件的增加密切相关。长期使用西地那非可通过增加凋亡导致听力损伤。

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Phosphodiesterase type 5 inhibitors and sudden sensorineural hearing loss.磷酸二酯酶 5 抑制剂与突发性感觉神经性耳聋。
Braz J Otorhinolaryngol. 2013 Nov-Dec;79(6):727-33. doi: 10.5935/1808-8694.20130133.
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PLoS One. 2013 Nov 14;8(11):e79226. doi: 10.1371/journal.pone.0079226. eCollection 2013.