尼群地平的抗5-HT作用与防治肺动脉高压的关系

Nitrendipine and 5 hydroxytryptamine in monocrotaline induced pulmonary hypertension

目的：探讨尼群地平（ Ｎ Ｉ Ｔ）对野百合碱（ Ｍ Ｃ Ｔ）性肺动脉高压的防治作用机理． 方法：用免疫组化方法和图像分析技术测定肺组织中五羟色胺（５ Ｈ Ｔ）及其受体的变化；采用 Ｍ Ｔ Ｔ 法和测微网及钙荧光指示剂 Ｆｕｒａ ２／ Ａｍ 测定培养的肺动脉平滑肌细胞（ Ｐ Ａ Ｓ Ｍ Ｃ）生长情况和收缩功能以及细胞内游离 Ｃａ２＋ 浓度． 结果：发现 Ｎ Ｉ Ｔ 能够显著地抑制 Ｍ Ｃ Ｔ 引起的５ Ｈ Ｔ 及其受体阳性细胞数目的增加和相对含量的增多．使５ Ｈ Ｔ及其受体阳性细胞数目从（１２７ ４９４±２０ ７３６）／ｍ ｍ ２和（１４ ６２４±３ ０１０）／ｍ ｍ ２ 分别减少到（２３ ８１４±１３ ２８４）／ｍ ｍ ２和（ ４ ８７５±９７２）／ｍ ｍ ２（ Ｐ＜ ０．０１）． 对５ Ｈ Ｔ引起培养的 Ｐ Ａ Ｓ Ｍ Ｃ增生和收缩都有显著的抑制作用． 这种抑制作用与其阻断５ Ｈ Ｔ 引起的 Ｃａ２＋ 内流有关． 结论： Ｎ Ｉ Ｔ不仅具有对抗５ Ｈ Ｔ的收缩血管作用和促 Ｐ Ａ Ｓ Ｍ Ｃ增殖作用， 而且还能抑制 Ｍ Ｃ Ｔ性肺动脉高压时肺组织中 ５ Ｈ Ｔ 阳性细胞的数量和 ５ Ｈ Ｔ 相对含量，这是 Ｎ Ｉ Ｔ 防治 Ｍ Ｃ Ｔ 性肺动脉高压的重要机制之一．

AIM: To explore the mechanism of nitrendipine (NIT) in the prevention and treatment of pulmonay hypertension induced by monocrotaline (MCT). METHODS: 5 hydroxytryptamine (5 HT) and 5 HT receptors (5 HTR) in pulmonary tissue were observed by immunohistochemistry and image analysis system. Cellular growth, constriction function and free Ca 2+ in cultured pulmonary arterial smooth muscle cells were measured by the methods of MTT, morphometry and calcium fluorescent probe Fura 2 Am. RESULTS: NIT restrained the number of MCT induced positivecells in pulmonary tissue (from 127 494±20 736 to 23 814±13 284/mm 2, P <0.01) and the relative contents( value of A: 1.16±0.26 to 0.30±0.17, P <0.01) of 5 HT and 5 HTR(from 14 624±3 010 to 4 875±972/mm 2, P <0.01, value of OD: 0.83±0.16 to 0.72±0.15) respectively. Both the cellular growth and the contraction of pulmonary arterial smooth muscle cells induced by 5 HT were inhibited significantly by NIT at 10 -8 mol/L. 5 HT induced (242±12 nmol/L) free Ca 2+ in cultured pulmonary arterial smooth muscle cells was prevented by NIT(126±9 nmol/L), which might be related to the inhibitory effect the NIT on the Ca 2+ influx. CONCLUSION: NIT can reduces the number and contents of 5 HT and 5 HT receptors in pulmonary tissue and plays an important role in the prevention and treatment of MCT induced pulmonary hypertension.