尼群地平对大鼠野百合碱性肺动脉高压的防治作用

Effect and mechanism of nitrendipine on pulmonary hypertension induced by monocrotaline

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+ .