卡托普利直接抑制持续不卧床腹膜透析治疗中的基质金属蛋白酶-2 活性。
Captopril directly inhibits matrix metalloproteinase-2 activity in continuous ambulatory peritoneal dialysis therapy.
机构信息
Biomedical Computation Center, Osaka Medical College, 2-7 Daigakuchou, Takatuski, 569-8686, Japan.
出版信息
Clin Chim Acta. 2010 May 2;411(9-10):762-4. doi: 10.1016/j.cca.2010.02.059. Epub 2010 Feb 22.
BACKGROUND
Matrix metalloproteinase (MMP)-2 plays an important role in tissue remodeling related to inflammation during continuous ambulatory peritoneal dialysis (CAPD) therapy. But its inhibitors were not applied clinically. We determined whether an angiotensin-converting enzyme (ACE) inhibitor, captopril, inhibits MMP-2 activity in peritoneal effluents from patients on CAPD, and simulated molecular models of the MMP-2-captopril complex.
METHODS
The inhibitory effect of captopril on MMP-2 activity was measured in peritoneal effluents from 17 patients on CAPD. Molecular models of the MMP-2-captopril complex were simulated by 1000 iterations of random docking and energy minimization.
RESULTS
Captopril directly inhibited MMP-2 activity in peritoneal effluents from patients on CAPD (IC50; 48 micromol/l), and that captopril binding to the MMP-2 active site could be formed in each complex model without molecular distortion.
CONCLUSION
ACE inhibitors, such as captopril, may be applied as important compounds for MMP-2 inhibition in inflammation caused by CAPD.
背景
基质金属蛋白酶（MMP）-2 在持续非卧床腹膜透析（CAPD）治疗过程中与炎症相关的组织重塑中发挥重要作用。但其抑制剂尚未在临床上应用。我们确定血管紧张素转换酶（ACE）抑制剂卡托普利是否抑制 CAPD 患者腹膜流出物中 MMP-2 的活性，并模拟 MMP-2-卡托普利复合物的分子模型。
方法
在 17 名 CAPD 患者的腹膜流出物中测量卡托普利对 MMP-2 活性的抑制作用。通过 1000 次随机对接和能量最小化迭代模拟 MMP-2-卡托普利复合物的分子模型。
结果
卡托普利直接抑制 CAPD 患者腹膜流出物中的 MMP-2 活性（IC50；48 μmol/L），并且在每个复合物模型中都可以形成卡托普利与 MMP-2 活性位点的结合，而不会发生分子变形。
结论
ACE 抑制剂，如卡托普利，可能作为 CAPD 引起的炎症中 MMP-2 抑制的重要化合物应用。
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