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磷酸二酯酶5抑制剂伐地那非长期治疗对部分膀胱出口梗阻模型雌性大鼠膀胱的影响。

Effects of chronic treatment with vardenafil, a phosphodiesterase 5 inhibitor, on female rat bladder in a partial bladder outlet obstruction model.

作者信息

Matsumoto Seiji, Hanai Tadashi, Uemura Hirotsugu, Levin Robert M

机构信息

Urological and Urodynamic Center, Koushinkai Hospital, Sakai, Osaka, Japan.

出版信息

BJU Int. 2009 Apr;103(7):987-90. doi: 10.1111/j.1464-410X.2008.08185.x. Epub 2008 Nov 13.

Abstract

OBJECTIVES

To investigate whether vardenafil, a phosphodiesterase 5 (PDE-5) inhibitor, would protect the bladder from decompensatory changes in a 4-week rat bladder outlet obstruction (BOO) model, as evidence has been accumulating that PDE-5 inhibitors improve lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH).

MATERIALS AND METHODS

In all, 50 12-week-old female Sprague-Dawley rats were divided into five equal groups; group 1, sham operated vehicle control rats; group 2, BOO vehicle rats; group 3-5, BOO rats given oral vardenafil at 5, 20, 80 mg/L, respectively. Vardenafil was given in drinking water from the day of surgery. At 4-weeks after the introduction of BOO, vardenafil was washed-out by giving water for 24-48 h, and then the bladder was excised and dissected into four longitudinal strips for isometric organ-bath assay. Contractile responses of bladder strips to electrical field stimulation (EFS), carbachol and KCl was determined for each group.

RESULTS

BOO induced a significant increase in bladder weight in group 2 compared with group 1. Bladder weights of groups 3-5 were not significantly different from that of group 2. The contractile forces in response to EFS, carbachol and KCl in group 2 were 30.7-51.7% of those in group 1. Vardenafil treatment in groups 3-5 generally did not block the BOO-induced reduction of contractile force in the bladder strips. However, treatment with a high dose of vardenafil resulted in a significant increase in the contractile response to carbachol (78.4% group 5 vs 51.7% group 2).

CONCLUSION

Chronic treatment with a high dose of vardenafil protected the rat bladder from BOO-induced contractile dysfunction to carbachol.

摘要

目的

磷酸二酯酶5(PDE - 5)抑制剂伐地那非是否能在为期4周的大鼠膀胱出口梗阻(BOO)模型中保护膀胱免于失代偿性改变,因为越来越多的证据表明PDE - 5抑制剂可改善良性前列腺增生(BPH)患者的下尿路症状(LUTS)。

材料与方法

总共50只12周龄雌性Sprague - Dawley大鼠被分为五组,每组数量相等;第1组,假手术溶剂对照大鼠;第2组,BOO溶剂大鼠;第3 - 5组,分别给予口服5、20、80 mg/L伐地那非的BOO大鼠。从手术当天起在饮水中给予伐地那非。在引入BOO 4周后,通过给予24 - 48小时水来洗脱伐地那非,然后切除膀胱并切成四个纵向条带用于等长器官浴分析。测定每组膀胱条带对电场刺激(EFS)、卡巴胆碱和氯化钾的收缩反应。

结果

与第1组相比,第2组中BOO导致膀胱重量显著增加。第3 - 5组的膀胱重量与第2组无显著差异。第2组中对EFS、卡巴胆碱和氯化钾的收缩力为第1组的30.7 - 51.7%。第3 - 5组中的伐地那非治疗通常未阻止BOO诱导的膀胱条带收缩力降低。然而,高剂量伐地那非治疗导致对卡巴胆碱的收缩反应显著增加(第5组为78.4%,第2组为51.7%)。

结论

高剂量伐地那非长期治疗可保护大鼠膀胱免于BOO诱导的对卡巴胆碱的收缩功能障碍。

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