依那普利拉对过氧化氢诱导的系膜细胞DNA合成的调节作用。

Modifying influence of enalaprilat on mesangial cell DNA synthesis induced by hydrogen peroxide.

作者信息

D'Souza R J, Phillips H M, Strange R C, Aber G M

机构信息

Renal and Clinical Biochemistry Research Laboratory, School of postgraduate Medicine, University of Keele, North Staffordshire Hospital Centre, UK.

出版信息

Clin Chim Acta. 1997 Mar 18;259(1-2):137-46. doi: 10.1016/s0009-8981(96)06480-7.

DOI:10.1016/s0009-8981(96)06480-7

PMID:9086301

Abstract

This study examined the effect of the angiotensin converting enzyme (ACE) inhibitor, enalaprilat, on mesangial cell (MC) DNA synthesis induced by H2O2, IL-6 and PDGF. MC were incubated with enalaprilat (2.5-100 mumol/l) alone and together with combinations of H2O2 (3 daily pulses of 10(-6) mol/l), IL-6 (5 ng/ml) and PDGF (10 ng/ml). DNA synthesis was assessed after 72 h using [3H]thymidine (3H-TdR) incorporation. Enalaprilat alone had no effect on MC DNA synthesis. Stimulation of MC by H2O2, PDGF and IL-6 alone resulted in increases in 3H-TdR of 4936.6 +/- 1147.5, 5640.5 +/- 1537.6 and 4413.5 +/- 998.4 cpm, respectively (P < 0.05 above control). Only 2.5 mumol/l enalaprilat effected a significant reduction in IL-6 and PDGF-induced DNA synthesis. Incubation of MC with H2O2 + PDGF or H2O2 + IL-6 resulted in increases of 3H-TdR of 6471.9 +/- 1785.1 and 5507.2 +/- 1270 cpm, respectively (P < 0.05 above control). Addition of enalaprilat with either H2O2 + PDGF or H2O2 + IL-6 effected significant reductions in DNA synthesis over the range 2.5-100 mumol/l. These data demonstrate that ACE inhibitors modulate MC DNA synthesis induced by reactive oxygen species.

摘要

本研究检测了血管紧张素转换酶（ACE）抑制剂依那普利拉对过氧化氢（H2O2）、白细胞介素-6（IL-6）和血小板衍生生长因子（PDGF）诱导的系膜细胞（MC）DNA合成的影响。将MC分别与依那普利拉（2.5 - 100 μmol/l）单独孵育，以及与H2O2（10⁻⁶ mol/l的3次每日脉冲）、IL-6（5 ng/ml）和PDGF（10 ng/ml）的组合共同孵育。72小时后使用[³H]胸腺嘧啶核苷（³H-TdR）掺入法评估DNA合成。依那普利拉单独使用对MC DNA合成无影响。单独用H2O2、PDGF和IL-6刺激MC导致³H-TdR分别增加4936.6±1147.5、5640.5±1537.6和4413.5±998.4 cpm（与对照组相比P < 0.05）。仅2.5 μmol/l依那普利拉能显著降低IL-6和PDGF诱导的DNA合成。MC与H2O2 + PDGF或H2O2 + IL-6孵育分别导致³H-TdR增加6471.9±1785.1和5507.2±1270 cpm（与对照组相比P < 0.05）。在2.5 - 100 μmol/l范围内，将依那普利拉与H2O2 + PDGF或H2O2 + IL-6一起添加能显著降低DNA合成。这些数据表明ACE抑制剂可调节活性氧诱导的MC DNA合成。