血管紧张素转换酶抑制剂对人中性粒细胞体外趋化性的影响。

The effect of angiotensin-converting enzyme inhibitors on human neutrophil chemotaxis in vitro.

Clapperton M, McMurray J, Fisher A C, Dargie H J

Department of Cardiology, Western Infirmary, Glasgow.

Br J Clin Pharmacol. 1994 Jul;38(1):53-6. doi: 10.1111/j.1365-2125.1994.tb04321.x.

Abstract

Myocardial 'reperfusion injury' has been partly attributed to the production of free radicals which are cytotoxic towards cells. Neutrophils are recruited by ischaemic tissue and are one source of free radicals. Angiotensin-converting enzyme (ACE) inhibitors can reduce 'reperfusion injury' and we decided to determine if ACE inhibitors might contribute to this effect by inhibiting neutrophil chemotaxis. 2. The effects of captopril (a thiol containing ACE inhibitor) and enalaprilat (a nonthiol ACE inhibitor) and N-mercaptopropionyl glycine (MPG) (a simple thiol) on neutrophil chemotaxis were tested in an in vitro Boyden chamber assay. 3. The chemotactic response of human neutrophils to fMLP was reduced by 27.6% with MPG (n = 8; P < 0.05), by 13.2% with enalaprilat (n = 8; P = 0.075) and by 5.2% with captopril (n = 8; P = 0.66) at 5 microM (therapeutic concentration.) 4. Neutrophil chemotaxis was significantly decreased with 50 microM and 500 microM MPG and enalaprilat and 500 microM captopril. 5. Supratherapeutic concentrations of ACE inhibitors can reduce neutrophil chemotaxis at high concentrations and this effect does not appear to be -SH dependent.

摘要

心肌“再灌注损伤”部分归因于对细胞具有细胞毒性的自由基的产生。中性粒细胞由缺血组织募集，是自由基的来源之一。血管紧张素转换酶（ACE）抑制剂可减轻“再灌注损伤”，我们决定研究ACE抑制剂是否可能通过抑制中性粒细胞趋化作用来发挥此效应。2. 在体外博伊登小室试验中测试了卡托普利（一种含硫醇的ACE抑制剂）、依那普利拉（一种非硫醇类ACE抑制剂）和N-巯基丙酰甘氨酸（MPG）（一种简单的硫醇）对中性粒细胞趋化作用的影响。3. 在5微摩尔（治疗浓度）时，MPG使人类中性粒细胞对fMLP的趋化反应降低了27.6%（n = 8；P < 0.05），依那普利拉降低了13.2%（n = 8；P = 0.075），卡托普利降低了5.2%（n = 8；P = 0.66）。4. 50微摩尔和500微摩尔的MPG、依那普利拉以及500微摩尔的卡托普利可显著降低中性粒细胞趋化作用。5. 超治疗浓度的ACE抑制剂在高浓度时可降低中性粒细胞趋化作用，且这种效应似乎不依赖于-SH。