2,6-二甲基-4-(2-氯苯基)-1,4-二氢-3,5-吡啶二羧酸二甲酯的抗5-羟色胺作用在防治野百合碱性大鼠肺动脉高压中的意义  

Significance of antiserotonin effect of dimethyl 4 (2 chlorophenyl) 1,4 dihydro 2,6 dimethyl 3,5 pyridinedicarboxylate in rat pulmonary hypertension induced by monocrotaline

作　　者：李志超[1,2] 张福琴[1,2] 赵德化[1,2] 黄威权 梅其炳[1,2] 孙本韬 

机构地区：[1]第四军医大学基础部药理学教研室 [2]山西医科大学电镜室

出　　处：《中国药理学与毒理学杂志》1999年第1期29-32,共4页Chinese Journal of Pharmacology and Toxicology

摘　　要：采用免疫组化，图像分析，细胞培养和细胞内游离钙离子浓度（［Ｃａ２＋］ｉ）测定等方法研究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）防治野百合碱（ＭＣＴ）所致肺动脉高压的作用机理．结果发现每天ｉｐＤＣＤＤＰ５－５００μｇ·ｋｇ－１１次，连续２８ｄ，能够明显地减少ＭＣＴ（６０ｍｇ·ｋｇ－１ｓｃ）引起的大鼠肺组织中５－ＨＴ相对含量及其受体阳性细胞数目增多，对５－ＨＴ引起的肺动脉平滑肌细胞增生，收缩及其［Ｃａ２＋］ｉ增高都有显著的抑制作用．结果提示，抑制肺组织中５－ＨＴ含量及其受体数目的增加，对抗５－ＨＴ引起的血管平滑肌细胞增生及收缩，可能是ＤＣＤＤＰ防治ＭＣＴ性肺动脉高压的重要机理之一．To explore the mechanism of dimethyl 4 (2 chlorophenyl) 1,4 dihydro 2,6 dimethyl 3,5 pyridinedicarboxylate (DCDDP) against pulmonary hypertension, it′s antiserotonin effect was investigated by using immunohistochemistry, image analysis, and Fura 2 AM assay of pulmonary arterial smooth muscle cells(PASMC) in culture. The results showed that DCDDP (5,50 and 500 μg·kg 1 ·d 1 ip,once a day for 28 day) inhibited the increase in numbers of 5 hydroxytryptamine(5 HT) positive cells and 5 HT receptor positive cells from (0.127±0.021) and (0.015±0.003) per μm 2 to (0.031±0.016) and (0.006±0.001), (0.039±0.018) and (0.005± 0.001), (0.059±0.017) and (0.007±0.001) per μm 2 (P<0.01) respectively in pulmonary tissue of pulmonary hypertensive rats induced by monocrotaline(MCT 60 mg·kg 1 sc). The proliferation and contraction of PASMC and increase in [Ca 2+ ] i of PASMC evoked by 5 HT were inhibited significantly by DCDDP. The results suggest that DCDDP reduce the content of 5 HT and the number of 5 HT receptor in pulmonary tissue, which may be one of the important mechanism of DCDDP against MCT induced pulmonary hypertension.

关 键 词：DCDDP 肺动脉高压 防治 钙通道阻滞药 野百合碱 

分 类 号：R972.4[医药卫生—药品]