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  • 彭永超,郑泽琪.金雀异黄酮、波生坦、他达拉非治疗野百合碱诱导的大鼠肺动脉高压疗效的比较[J].第二军医大学学报,2017,38(8):997-1003    [点击复制]
  • PENG Yong-chao,ZHENG Ze-qi.Genistein, bosentan and tadalafil in treatment of monocrotaline-induced pulmonary arterial hypertension in rats: a comparison of efficacy[J].Acad J Sec Mil Med Univ,2017,38(8):997-1003   [点击复制]
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金雀异黄酮、波生坦、他达拉非治疗野百合碱诱导的大鼠肺动脉高压疗效的比较
彭永超,郑泽琪*
0
(南昌大学第一附属医院心内科, 江西省高血压病研究所, 南昌 330000
*通信作者)
摘要:
目的 比较金雀异黄酮、波生坦、他达拉非治疗野百合碱诱导大鼠肺动脉高压的疗效。方法 SD大鼠一次性腹腔注射野百合碱(50 mg/kg)诱导肺动脉高压模型(n=48),对照组大鼠(n=8)给予腹腔注射生理盐水。3周成功建模后分为肺动脉高压组(生理盐水灌胃)、金雀异黄酮不同剂量组[G30、G60、G120组,分别给予金雀异黄酮30、60、120 mg/(kg·d)剂量灌胃]、波生坦组[波生坦5 mg/(kg·d)灌胃]、他达拉非组[他达拉非0.5 mg/(kg·d)灌胃],每组8只。对照组大鼠予以生理盐水灌胃。干预2周后,比较各组生存率、右房室瓣反流速度、肺动脉内径、平均肺动脉压力、血管舒张功能、右心室肥厚指数、肺组织病理情况。结果 与对照组相比,肺动脉高压组大鼠右房室瓣反流速度增快,肺动脉内径增宽,平均肺动脉压升高、右心室肥厚指数升高,差异均有统计学意义(P<0.05)。而与肺动脉高压组相比,金雀异黄酮能降低野百合碱诱导的肺动脉高压大鼠的右房室瓣反流速度(G60、G120)、肺动脉内径(G120)、平均肺动脉压(G30、G60、G120)、右心室肥厚指数(G60、G120),提高大鼠生存率(G120)及内皮依赖性舒张功能(G30、G60、G120),改善肺血管管腔狭窄、管壁增厚、血管平滑肌细胞增殖(G30、G60、G120),差异均有统计学意义(P<0.05),但上述作用均次于波生坦、他达拉非组(P<0.05)。结论 金雀异黄酮对野百合碱诱导的大鼠肺动脉高压有一定治疗效果,虽其疗效不及波生坦、他达拉非,但金雀异黄酮价格低廉、容易获得、不良反应少,有望成为治疗肺动脉高压的新型辅助药物。
关键词:  肺动脉高压  金雀异黄酮  波生坦  他达拉非
DOI:10.16781/j.0258-879x.2017.08.0997
投稿时间:2016-12-16修订日期:2017-06-03
基金项目:江西省科技计划项目(20142BBG70057).
Genistein, bosentan and tadalafil in treatment of monocrotaline-induced pulmonary arterial hypertension in rats: a comparison of efficacy
PENG Yong-chao,ZHENG Ze-qi*
(Department of Cardiology, the First Affiliated Hospital of Nanchang University, Hypertension Research Institute of Jiangxi, Nanchang 330000, Jiangxi, China
*Corresponding author)
Abstract:
Objective To compare the effects of genistein, bosentan, and tadalfil in treatment of monocrotaline-induced pulmonary arterial hypertension (PAH) in rats. Methods Monocrotaline-induced PAH SD-rat model was established by injecting monocrotaline (50 mg/kg) intraperitoneally (n=48), while the rats in control group (n=8) were given normal saline injection. Then all model rats were randomly divided into 6 groups (n=8) according to different drugs given by gavage after 3 weeks:PAH group (PAH rats were treated with normal saline), genistein G30, G60, G120 groups (PAH rats were treated with genistein 30, 60, 120 mg·kg-1·d-1, respectively), bosentan group (PAH rats were treated with bosentan 5 mg·kg-1·d-1), and tadalafil group (PAH rats were treated with tadalafil 0.5 mg·kg-1·d-1). After 2 weeks of treatment, survival rate, tricupid regurgitation (TR), pulmonary artery diameter (PAD), mean pulmonary arterial pressure (PAP), acetylcholine (ACh)-induced endothelium-dependent relaxation (EDdR), sodium nitroprusside (SNP)-induced endothelium-independent relaxation (EDiR), right ventricular hypertrophy index (RVHI), and lung phathological of rats in each group were compared. Results Compared with the control group, the TR, PAD, mean PAP and RVHI of rats were significantly increased in PAH group (P<0.05). Compared with the PAH group, the TR and RVHI of rats were significantly decreased in G60 and G120 groups, PAD was significantly decreased in G120 group, mean PAP was significantly decreased in G30, G60 and G120 groups, survival rate was significantly increased in G120 group, and endothelium-dependent relaxation was significantly improved in G30, G60 and G120 groups, while pulmonary vascular luminal stenosis, wall thickening and vascular smooth muscle cell proliferation were significantly inhibited in G30, G60 and G120 groups (P<0.05). However, the above effects of genistein were less than bosentan and tadalafil (P<0.05). Conclusion Genistein has a certain effect on monocrotaline-induced PAH in rat; although its efficacy is less than that of bosentan and tadalafil, genistein is cheaper, easy to obtain and has less side effects, and is also expected to be a new auxiliary drug for PAH.
Key words:  pulmonary arterial hypertension  genistein  bosentan  tadalafil