摘要
目的:钙通道阻滞剂是临床上最常用的血管扩张剂之一。但近年来,随着新型钙通道阻滞剂的应用,钙通道阻滞剂的多效性得到研究,一些钙通道阻滞剂治疗的益处除扩张血管作用外尚有其他作用,故了解钙通道阻滞剂的多效性将有助于进一步阐明钙通道阻滞剂治疗机制及合理使用钙通道阻滞剂。资料来源:应用计算机检索Pubmed数据库1982-01/2006-01有关钙通道阻滞剂氨氯地平的文章,检索词“calciumantagonist,amlodipine,enantiomer,isomer,racemicmixture”,限定文章语言种类为English。资料选择:对资料进行初审,选取符合研究要求的有关文章找全文。纳入标准:①有关氨氯地平的理化特性及其与胆固醇和氧自由基相互作用的研究。②有关氨氯地平调节一氧化氮的生成和意义的研究。③氨氯地平在控制平滑肌细胞增生和基质形成中作用的研究。排除标准:重复研究。资料提炼:共收集到231篇有关氨氯地平L-型钙通道阻滞作用以外的血管生物学特性的文章,排除重复或类似的同一研究,21篇最符合研究要求。资料综合:①氨氯地平的理化特性及其与胆固醇和氧自由基的相互作用的研究:氨氯地平在胞膜的浓度比膜外浓度高出1000倍以上,为长效的钙通道阻滞剂,且即使在细胞膜富含高胆固醇动脉粥样硬化时,和细胞膜仍具有较高的亲和力,从而逆转胆固醇对膜结构和功能的不良影响。②氨氯地平调节一氧化氮的生成和意义的研究:氨氯地平可刺激内皮一氧化氮合成酶异构体的形成,但氨氯地平对一氧化氮释放具有对应体特异性,即左旋氨氯地平则对血管内一氧化氮的生成没有影响,右旋氨氯地平能激活内皮一氧化氮合成酶。③氨氯地平在控制平滑肌细胞增生和基质形成中作用的研究:氨氯地平减轻血管平滑肌细胞增生的机制可能为:氨氯地平对钙信号的影响;一氧化氮的生成及抗氧化作用;其他作用。结论:氨氯地平除具有L-型钙通道阻滞剂的特性外,还具有非L-型钙通道阻滞剂相关的多效性。了解氨氯地平L-型钙通道阻滞作用以外的血管生物学特性具有重要临床意义。
OBJECTIVE：Calcium antagonist is one of vasodilating agents that widely used in clinic. However, with the evolution of calcium antagonist progress in recent years, more work are done to study the pleiotropic effects. There are some other effects of calcium antagonist treatment beyond vasodilatation. Therefore, to understand the pleiotropic effects of calcium antagonist will greatly contribute to explain its therapeutic mechanism as well as how to make use of calcium antagonist rationally. DATA SOURCES：A computer-based search was conducted in Pubmed database for papers published between January 1982 to January 2006 about calcium antagonist amlodipine with the key words of ＂calcium antagonist,amlodipine, enantiomer, isomer and raeemie mixture＂, and the language was limited to English. STUDY SELECTION：Data were checked in the first trial, and articles met the inclusion criteria were looked for the full text. Inclusion criteria： ① Researches about the physicochemical characteristics of amlodipine and its interaction with cholesterol and oxygen free radical. ② Articles about amlodipine in regulating the production of nitrogen monoxidum （NO）. ③ Literatures on the effect of amlodipine in manipulating the proliferation of vascular smooth muscle cells as well as the formation of matrix. Exclusion criteria： Repetitive studies. DATA EXTRACTION：A total of 231 papers about the vascular bionomics of amlodipine beyond the blocking effect of L-type calcium channel were collected. Repetitive studies or similar researches were excluded, and 21 literatures met the inclusion criteria. DATA SYNTHESIS： ① Studies about the physicochemical characteristics of amlodipine and its antioxidant properties： The concentration of amlodipine in membrane was 10 000 times higher than that outside the membrane, which was a long-lasting calcium antagonist. Moreover, there was high affinity preserved in the membrane even under atherosclerosis-like conditions characterized by an increase in membrane cholesterol content, and thus eliminate the side-effect of cholesterol on the structure and function of cholesterol.② Research on amlodipine stimulates NO synthesis： Amlodipine could stimulate the synthesis of isomeride in endothelial nitric oxide synthetase. However, the amlodipine had enantiomer-specificity on the release of NO, i.e. R＋ amlodipine has this function while L-amlodipine has not. ③ Studies about the effect of amlodipine in regulating the proliferation of vascular smooth muscle cells and the formation of matrix： The reduction mechanism of amlodipine on vascular smooth muscle cell proliferation may be as follows： The effects of amlodipine on calcium signals; the effect on NO production/release and its antioxydation; other effects. CONCLUSlON：Amlodipine not only has the characteristic of L-type calcium antagonist but also has pleiotropic effects of non-L-type calcium antagonist. It has important significance in clinic to further understand the vascular and biological characteristics of amlodipine beyond L-type calcium antagonist.
出处
《中国临床康复》
CSCD
北大核心
2006年第45期142-144,共3页
Chinese Journal of Clinical Rehabilitation
