摘要
目的:利用野百合碱(MCT)引起的大鼠肺动脉高压(PH)模型,探讨尼群地平(NIT)对MCT性PH的防治作用。方法:给MCT或MCT+NIT(10mg·kg-1ip,每日一次)4wk,测定肺血流动力学参数和静脉血浆及肺组织匀浆中内皮素样免疫反应物(ir-ET)、一氧化氮(NO)、超氧化物歧化酶(SOD)和丙二醛(MDA)的含量。结果:NIT能有效地降低MCT模型大鼠的肺动脉压(从4.5±0.9降至3.6±0.5kPa)和肺血管阻力(从118±17降至79±18kPa·min·L-1),能抑制MCT引起的肺小动脉中膜增厚;NIT能显著抑制MCT模型大鼠的肺组织匀浆中NO含量的减少和血浆中SOD活性的降低(P<0.05),明显阻止肺匀浆中MDA的升高(P<0.01)。结论:长期使用NIT可有效防治MCT性PH,其作用可能与其Ca2+拮抗作用及保护SOD活性和增加NO含量有关。
Objective\ To explore the effect and mechanism of nitrendipine (NIT) on pulmonary hypertension (PH), adult male Sprague Dawley rats were given a single subcutaneous injection of monocrotaline (MCT, 60 mg·kg -1 ) to induce the mold of PH. Methods\ Rats were given injection of NIT (10 mg·kg -1 ) by ip 30 min before and once daily after MCT injection for 4 weeks. The parameters of pulmonary hemodynamics were monitored. Concentration of endothelin like immunoreactivity (ir ET), nitric oxide (NO), malondialdehyde (MDA) and activity of superoxide dismutase (SOD) in plasma and pulmonary homogenate measured by radioimmunoassay and colorimetric analysis. Results\ Contineous injection of NIT significantly inhibited the progression of pulmonary artery pressure (3 6±0 5 versus 4 5±0 9 kPa) and pulmonary vascular resistance (79±18 versus 118±17 kPa·min·L -1 ). Histological examination revealed that NIT also effectively prevented pulmonary arterial medial thickening. NIT significantly raised both concentration of NO(16±7 versus 0 6±0 4 μmol·L -1 ) in pulmonary homogenate and activity of SOD (144±18 versus 106±45 NU·ml -1 ) in plasma and depressed the increase of MDA concentration. Conclusions Contineously using NIT can effectively prevent pulmonary hypertension induced by MCT of which mechanism may be partly related to the increase in activity of SOD and concentration of NO besides its inhibition of inflow of Ca 2+ .
出处
《中国药理学通报》
CAS
CSCD
北大核心
1997年第2期144-147,共4页
Chinese Pharmacological Bulletin
关键词
肺动脉高压
野百合碱性
尼群地平
内皮素
hypertension
pulmonary artery
monocrotaline
nitrendipine
endothelin
nitric oxide
superoxide dismutase
malondialdehyde