2,6-二甲基-4-(2-氯苯基)-1,4-二氢-3,5-吡啶二羧酸二甲酯对大鼠野百合碱性肺动脉高压的防治作用

Effect of dimethyl 4 (2 chlorophenyl) 1,4 dihydro 2,6 dimethyl 3,5 pyridinedicarboxylate on the chronic pulmonary hypertension induced by monocrotaline in rats

用野百合碱（ＭＣＴ）复制大鼠慢性肺动脉高压（ＰＨ）病理模型，探讨钙拮抗剂２，６－二甲基－４－（２－氯苯基）－１，４－二氢－３，５－吡啶二羧酸二甲酯（ＤＣＤＤＰ）对ＰＨ的防治作用．ＤＣＤＤＰ５，５０，５００μｇ·ｋｇ－１ｉｐ，每日１次，连续２８ｄ；ＭＣＴ６０ｍｇ·ｋｇ－１在第１次给ＤＣＤＤＰ后３０ｍｉｎｓｃ．观察肺血流动力学指标变化，血浆和肺匀浆中内皮素样免疫反应物（ｉｒ－ＥＴ），一氧化氮（ＮＯ）含量，超氧化物歧化酶（ＳＯＤ）活性和丙二醛（ＭＤＡ）含量的改变．三种不同剂量的ＤＣＤＤＰ分别使平均肺动脉压从４．５±０．９ｋＰａ（ＭＣＴ组）降至３．２±０．２，３．５±０．６和３．８±０．９ｋＰａ，肺血管阻力从１１８±１７ｋＰａ·ｍｉｎ－１·Ｌ－１（ＭＣＴ组）降至６５±１６，６８±１８和７６±１８ｋＰａ·ｍｉｎ－１·Ｌ－１（Ｐ＜０．０１），提示在本实验剂量范围内，中，低剂量ＤＣＤＤＰ防治效果似较好．ＤＣＤＤＰ不影响ＭＣＴ性ＰＨ时血浆和肺匀浆中ｉｒ－ＥＴ的改变，但可显著升高肺匀浆中ＮＯ的含量和ＳＯＤ活性，使肺匀浆中ＭＤＡ含量降至正常，这可能是其降低肺动脉压的机理之一．

The effect of dimethyl 4 (2 chlorophenyl) 1,4 dihydro 2,6 dimethyl 3,5 pyridinedicarboxylate (DCDDP, 5, 50, 500 μg·kg 1 ip, once a day for 28 d), a dihydropyridine calcium antagonist, on the chronic pulmonary hypertension (PH) induced by monocrotaline (MCT, 60 mg·kg 1 sc, 30 min after the first injection of DCDDP) in Sprague Dawley rats was investigated.The parameters of pulmonary hemodynamics were monitored. The contents of endothelin like immunoreactivity (ir ET) and nitric oxide (NO), superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentration in plasma and pulmonary homogenate were measured. The pulmonary artery pressure was droped from 4.5±0.9 kPa (MCT group) to 3.2±0.2, 3.5±0.6 and 3.8±0.9 kPa by these three doses of DCDDP, respectively; and the pulmonary resistance was decreased from 118±17 kPa·min 1 ·L 1 (MCT group) to 65±16, 68±18 and 76±18 kPa·min 1 ·L 1 respectively 28 d after injection of MCT, suggesting that the middle and low doses of DCDDP may be more effective than the high dose. DCDDP had no influence on ir ET levels in plasma and pulmonary homogenate, but inhibited the decrease in the content of NO and the activity of SOD and prevented the elevation of the content of MDA in pulmonary homogenate by MCT. It is concluded that the mechanism of DCDDP for lowering pulmonary artery pressure may be related to inhibit the production of free radical and increase in the content of NO in lungs.