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血管紧张素转换酶抑制剂对川崎病患者基质金属蛋白酶-9 活性的影响。

Effect of angiotensin-converting enzyme inhibitor on matrix metalloproteinase-9 activity in patients with Kawasaki disease.

机构信息

Department of Pharmacology, Osaka Medical College, Takatsuki 569-8686, Japan.

出版信息

Clin Chim Acta. 2010 Feb;411(3-4):267-9. doi: 10.1016/j.cca.2009.11.020. Epub 2009 Nov 27.

Abstract

BACKGROUND

Matrix metalloproteinase (MMP)-9 is thought to be involved in coronary artery aneurysms (CAAs) in patients with Kawasaki disease (KD); however, MMP-9 inhibitors are not used clinically. This study investigated whether the angiotensin-converting enzyme (ACE) inhibitor captopril could inhibit serum MMP-9 activity using serum from KD patients in an in vitro experiment.

METHODS

In 7 KD patients, serum MMP-9 activity was measured using the MMP-9 assay kit 3 times: before and after intravenous immunoglobulin (IVIG) treatment, and during the convalescent phase. The effect of captopril on MMP-9 activity was also assessed using serum obtained before IVIG treatment.

RESULTS

Serum MMP-9 activity was significantly higher during the pre-treatment phase than during the post-treatment and convalescent phases. MMP-9 activity during the pre-treatment phase was dose-dependently inhibited by captopril, and the IC(50) for MMP-9 was 500nM. The potency of captopril for MMP-9 inhibition was comparable to that for ACE inhibition.

CONCLUSION

ACE inhibitor may be effective for preventing CAA formation in KD patients, especially IVIG non-responders.

摘要

背景

基质金属蛋白酶-9(MMP-9)被认为与川崎病(KD)患者的冠状动脉瘤(CAA)有关;然而,MMP-9 抑制剂并未在临床上应用。本研究通过体外实验,探讨血管紧张素转换酶(ACE)抑制剂卡托普利能否抑制 KD 患者血清中 MMP-9 的活性。

方法

对 7 例 KD 患者的血清 MMP-9 活性进行 3 次检测:静脉注射免疫球蛋白(IVIG)治疗前、治疗后和恢复期。同时,在 IVIG 治疗前也评估了卡托普利对 MMP-9 活性的影响。

结果

治疗前血清 MMP-9 活性明显高于治疗后和恢复期。卡托普利可剂量依赖性地抑制 MMP-9 活性,MMP-9 的 IC50 为 500nM。卡托普利对 MMP-9 的抑制作用与 ACE 抑制作用相当。

结论

ACE 抑制剂可能对预防 KD 患者 CAA 的形成有效,特别是对 IVIG 无反应者。

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