天津医药

天津医药 ›› 2015, Vol. 43 ›› Issue (3): 256-258.doi: 10.11958/j.issn.0253-9896.2015.03.009

• 实验研究 • 上一篇    下一篇

伐地那非对模拟高原低氧性肺动脉高压大鼠的作用

周晓玲， 潘磊， 马婷婷， 郭蕊， 王勇   

  1. 首都医科大学附属北京世纪坛医院老年医学科， 首都医科大学附属北京世纪坛医院低氧实验室(邮编100038)
  • 收稿日期:2014-09-16 修回日期:2014-11-12 出版日期:2015-03-15 发布日期:2015-03-15
  • 通讯作者: 王勇 E-mail:wangyong7096@yahoo.com.cn
  • 作者简介:周晓玲 （1982）， 女， 博士， 主要从事老年医学、 低氧医学研究
  • 基金资助:
    北京市中医药科技项目(JJ2013-10)

The effects of vardenafil on high altitude pulmonary hypertension in rats

ZHOU Xiaoling, PAN Lei, MA Tingting, GUO Rui, WANG Yong   

  1. Department of Geratology, Hypoxia Laboratory, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China

  • Received:2014-09-16 Revised:2014-11-12 Published:2015-03-15 Online:2015-03-15
  • Contact: WANG Yong E-mail:wangyong7096@yahoo.com.cn

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摘要： 目的 探讨伐地那非防治高原低氧性肺动脉高压大鼠的效果及可能机制。方法 将 30 只大鼠随机分为常压常氧对照组(C 组)、 低压低氧组(P 组)和低压低氧+伐地那非组(V 组)， 每组 10 只。采用低压低氧舱模拟海拔5 000 m 的高原环境(大气压 50 kPa， 氧浓度 10%)， P 组和 V 组大鼠每日入舱 8 h， V 组大鼠每日入舱前给伐地那非 1mg/kg 灌胃 1 次， C 组和 P 组每日给予等剂量蒸馏水灌胃 1 次， 共 4 周。4 周后比较各组大鼠的平均肺动脉压、 右心肥厚指数、 肺血管显微形态学以及血清 NO、 内皮素-1(ET-1)水平。结果 P 组的肺动脉压、 右心肥厚指数、 肺小动脉管壁厚度占血管外径的百分比(WT%)和管壁面积占血管总面积的百分比(WA%)显著高于 C 组和 V 组(P < 0.05)， 血清 NO 低于 C 组和 V 组(P < 0.05)， ET-1 高于 C 组和 V 组(P < 0.05)。结论 伐地那非能降低高原肺动脉高压的肺动脉压力， 减轻肺血管及右心重构。

关键词: 高血压, 肺性； 磷酸二酯酶抑制剂； 一氧化氮； 内皮缩血管肽 1； 高原性肺动脉高压； 伐地那非

Abstract: Objective To investigate the effect of vardenafil on high altitude pulmonary hypertension in rats, and the possible mechanism thereof. Methods Thirty rats were randomly divided into three groups: control group with normal-pressure and normal-oxygen (group C), pulmonary hypertension group with low-pressure and low-oxygen (group P), and the group treated by vardenafil in low-pressure and low-oxygen condition (group V). The rats of group P and group V were exposed to low-pressure and low-oxygen condition in an auto-modulating hypobaric and hypoxic cabin to simulate 5 000 m high altitude environment (air pressure 50 kPa, oxygen concentration 10%) for 8 hours daily. Vardenafil (1 mg/kg) was given by gastrogavage to rats in group V once daily for 4 weeks, while the isodose distilled water was given by gastrogavage to rats in group C and group P. The mean pulmonary arterial pressure and right ventricular mass index were measured respectively
after 4-week treatment. Morphologic changes of peripheral pulmonary artery were detected by light microscope. The serum levels of nitric oxide (NO) and endothelin-1 (ET-1) were detected as well. Results The pulmonary arterial pressure and right ventricular mass index were significantly higher in group P than those of group C and group V (P < 0.05). The ratio of vascular medial wall thickness to external diameter (WT%) and the ratio of pulmonary artery wall area to tube area (WA%) were significantly increased in group P than those of group C and group V (P < 0.05). Furthermore, the serum level of NO was significantly lower in group P than that of group C and group V, but the serum level of ET-1 was significantly increased compared with that of group C and group V (P < 0.05). Conclusion Vardenafil can effectively reduce the pulmonary arterial pressure, and attenuate pulmonary vessels and right ventricle remodeling induced by high altitude pulmonary hypertension.

Key words: hypertension, pulmonary, phosphodiesterase inhibitors;nitric oxide, endothelin-1, high altitude pulmonary hypertension, vardenafil