钙拮抗剂和ACEI对主动脉平滑肌细胞增殖的影响

Effect of Different Calcium Antagonists and ACEIs on Proliferation of Human Aortic Vascular Smooth Muscle Cells

该研究以培养人体血管平滑肌细胞（ＶＳＭＣ）为模型，用３Ｈ－ＴｄＲ掺入试验观察钙拮抗剂（Ｎｉｆｅｄｉｐｉｎｅ、Ａｍｌｏｄｉｐｉｎｅ）和ＡＣＥＩ（Ｃｉｌａｚａｐｒｉｌ、Ｂｅｎａｚａｐｒｉｌ）对细胞增殖效应。结果３种浓度钙拮抗剂都明显抑制细胞增殖（Ｐ＜０．０１），高浓度（１０－５ｍｏｌ／Ｌ、５×１０－６ｍｏｌ／Ｌ）时Ｎｉｆｅｄｉｐｉｎｅ抑制程度更好（Ｐ＜０．０５），低浓度（１０－６ｍｏｌ／Ｌ）以Ａｍｌｏｄｉｐｉｎｅ为佳（Ｐ＜０．０５）。ＡＣＥＩ中发现高浓度时２种药物均能抑制细胞增殖（Ｐ＜０．０１），而低浓度时细胞生长反常地超过对照组（Ｐ＜０．０５）。钙拮抗剂与ＡＣＥＩ比较，前者尤其是Ｎｉｆｅｄｉｐｉｎｅ抑制细胞增殖程度较ＡＣＥＩ明显。由此推测小剂量ＡＣＥＩ反而刺激细胞增生是否与药物含量较低时仅抑制血浆ＡＣＥ活性，不能抑制组织ＡＣＥ活性有关。

Proliferation of vascular smooth muscle cells(VSMCs)plays a key role in the evolution of restenosis after coronary angioplasty. An observation was made on the effect of calcium antagonists(Nifedipine,Amlodipine) and ACEIs(Cilazapril, Benazapril)on cultured human VSMCs using 3H-TdR incorporation as parameter for growth. Our resulte showed that all three different concentrations of the calcium antagonists inhibited VSMC growth significantly(P< 0.01);high concentration Nifedipine yielded a better result;while at low concentration, Amlodipine seemed to show a greater inhibition。 As to ACEIs both Cilazapril and Benazapril in high concentration inhibited growth of VSMCs;however at low concentration VSMCs growth paradoxically increased compared to control.Between calcium antagoniste and ACEls, the former showed a greater inhibition. It was postulated that low concentration of ACEIs was not able to inhibit VSMC growth,A search for potent tissue ACEIs was not able to inhibit VSMC growth,A search for potent tissue ACEIs may be the solution for prevention of restenosis after coronary angioplasty。