伐地那非对模拟高原低氧性肺动脉高压大鼠的作用
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- 英文论文题名：The effects of vardenafil on high altitude pulmonary hypertension in rats
- 论文作者：周晓玲 ; 潘磊 ; 马婷婷 ; 郭蕊 ; 王勇
- 英文论文作者：ZHOU Xiaoling ; PAN Lei ; MA Tingting ; GUO Rui ; WANG Yong ; Department of Geratology ; Hypoxia Laboratory ; Beijing Shijitan Hospital ; Capital Medical University
- 年：2016
- 作者机构：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;
- 论文关键词：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
- 英文论文关键词：hypertension ; pulmonary ; phosphodiesterase inhibitors ; nitrie oxide ; endothelin-1 ; high altitude pulmonary hypertension ; vardenafil
- 会议召开时间：2016-06-25
- 会议录名称：青藏铁路运营十周年学术研讨会卫生系统论文集
- 语种：中文
- 分类号：R544.1
- 学会代码：ZGTD
- 会议名称：青藏铁路运营十周年学术研讨会
- 会议地点：中国西藏拉萨
- 主办单位：中国铁道学会、青海省科学技术协会、西藏自治区科学技术协会
- 学会名称：中国铁道学会
- 页数：4
- 文件大小：1248k
- 原文格式：O
- 会议级别：全国
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。
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 rate 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 mieroseope.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.
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 rate 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 mieroseope.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.
引文
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[5]Bates MG,Thompson AA,Baillie JK,et al.Sildenafil citrate for the prevention of high altitude hypoxic pulmonary hypertension:double blind,randomized,placebo-controlled trial[J].High Alt Med Biol,2011,12(3):207-214.
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[7]Fan YF,Zhang R,Jiang X,et al.The phosphodiesterase-5 inhibitor vardenafil reduces oxidative stress while reversing pulmonary arterial hypertension[J].Cardiovas Res,2013,99(3):395-403.
[8]Maggiorini M,Leon-Velarde F.High-altitude pulmonary hypertension:pathophysiological entity to different diseases[J].Eur Respir J,2003,22(6):1019-1025.
[9]Ghofrani HA,Pepke-Zaba J,Barbera JA,et al.Nitric oxide pathway and phosphodiesterase inhibitors in pulmonary arterial hypertension[J].J Am Coll Cardiol,2004,43(12 Suppl S):68S-72S.
[10]Gong XL,Zhu LM,Cai XM,et al.The rapeutic effect of vardenafil on pulmonary hypertension after operation for congenital heart disease[J].Journal of Shanghai Jiaotong Uruveraity(Medical Science),2011,30(9):1287-1290.[龚霄雷,朱丽敏,蔡小满,等.伐地那非治疗先天性心脏病术后肺动脉高压的疗效观察[J].上海交通大学学报医学版,2011,30(9):1287-1290].
[11]Jing ZC,Yu ZX,Shen JY,et al.Vardenafil in pulmonary arterial hypertension:a randomized,double-blind,placebo-controlled study[J].Am J Respir Crit Care Med,2011,183(12):1723-1729.
[12]Elvert G,Kappel A,Heidenreich R,et al.Cooperative interaction of hypoxia inducible factor-2a(hif-2a)and Ets-1 in the transcritional activation of vascular endothelial growth factor receptor-2(Flk-1)[J].J Biol Chem,2003,278(9):7520-7530.
[2]Xu XQ,Jing ZC.High-altitude pulmonary hypertension[J].Eur Respir Rev,2009,18(111):13-17.
[3]Seferian A,Simonneau G.Therapies for pulmonary arterial hypertension:where are we today,where do we go tomorrow[J]?Eur Respir Rev,2013,22(129):217-226.
[4]Xu Y,Liu Y,Liu J,et al.Meta-analysis of clinical efficacy of sildenafil,a phosphodiesterase type-5 inhibitor on high altitude hypoxia and its complications[J].High Alt Med Biol,2014,15(1):46-51.
[5]Bates MG,Thompson AA,Baillie JK,et al.Sildenafil citrate for the prevention of high altitude hypoxic pulmonary hypertension:double blind,randomized,placebo-controlled trial[J].High Alt Med Biol,2011,12(3):207-214.
[6]Togue HA,Teixeira CE,Priviero FB,et al.Vardenafil,but not sildenafil or tadalafil,has calcium-channel blocking activity in rabbit isolatedpulmonary artery and human washed platelets[J].Br J Pharmacol,2008,154(4):787-796.
[7]Fan YF,Zhang R,Jiang X,et al.The phosphodiesterase-5 inhibitor vardenafil reduces oxidative stress while reversing pulmonary arterial hypertension[J].Cardiovas Res,2013,99(3):395-403.
[8]Maggiorini M,Leon-Velarde F.High-altitude pulmonary hypertension:pathophysiological entity to different diseases[J].Eur Respir J,2003,22(6):1019-1025.
[9]Ghofrani HA,Pepke-Zaba J,Barbera JA,et al.Nitric oxide pathway and phosphodiesterase inhibitors in pulmonary arterial hypertension[J].J Am Coll Cardiol,2004,43(12 Suppl S):68S-72S.
[10]Gong XL,Zhu LM,Cai XM,et al.The rapeutic effect of vardenafil on pulmonary hypertension after operation for congenital heart disease[J].Journal of Shanghai Jiaotong Uruveraity(Medical Science),2011,30(9):1287-1290.[龚霄雷,朱丽敏,蔡小满,等.伐地那非治疗先天性心脏病术后肺动脉高压的疗效观察[J].上海交通大学学报医学版,2011,30(9):1287-1290].
[11]Jing ZC,Yu ZX,Shen JY,et al.Vardenafil in pulmonary arterial hypertension:a randomized,double-blind,placebo-controlled study[J].Am J Respir Crit Care Med,2011,183(12):1723-1729.
[12]Elvert G,Kappel A,Heidenreich R,et al.Cooperative interaction of hypoxia inducible factor-2a(hif-2a)and Ets-1 in the transcritional activation of vascular endothelial growth factor receptor-2(Flk-1)[J].J Biol Chem,2003,278(9):7520-7530.