D'Souza R J, Phillips H M, Radeke H H, Aber G M, Strange R C
Renal and Clinical Biochemistry Research Laboratories, School of Postgraduate Medicine, University of Keele, North Staffordshire Hospital Centre, Stoke on Trent, UK.
Nephron. 1996;72(2):263-8. doi: 10.1159/000188852.
This study indirectly examined the role of prostanoids (PG) in mediating rat mesangial cell (MC) DNA synthesis induced by hydrogen peroxide (H2O2), interleukin 6 (IL-6), and platelet-derived growth factor (PDGF). MC were exposed to three daily pulses of 10(-6) mol/l H2O2 alone or in combination with IL-6 (5 ng/ml) or PDGF (10 ng/ml). In order to examine (indirectly) the role of PG in mediating changes in MC DNA synthesis, indomethacin (1.5 x 10(-5) mol/l) or the thromboxane A2 synthetase inhibitor Dazmegrel (10(-5) mol/l) was added to the medium and DNA synthesis assessed after 72 h using 3H-thymidine incorporation (3H-TdR). Stimulation of MC by H2O2 alone resulted in an increase in 3H-TdR of 34.7 +/- 5.5% (p < 0.01). H2O2 enhanced the mitogenic effects of IL-6 and PDGF, 3H-TdR increasing by 52 +/- 12.1% (p < 0.01) and 100 +/- 21% (p < 0.001), respectively. Indomethacin suppressed the DNA synthesis induced by H2O2 alone, 3H-TdR decreasing by 33 +/- 12% (p < 0.05). Indomethacin also reduced the mitogenic response to H2O2 plus IL-6 and H2O2 plus PDGF by 91 +/- 17 and 97 +/- 12%, respectively (p < 0.05). Dazmegrel reduced 3H-TdR when MC were exposed to H2O2 alone by 31.8 +/- 16% (p < 0.05) and when combined with IL-6 or PDGF by 80 +/- 26 and 120 +/- 13%, respectively (p < 0.05). These data suggest that the pathways through which H2O2-induced growth of MC is mediated appear, at least in part, to involve PG, particularly thromboxane A2.
本研究间接检测了前列腺素（PG）在介导过氧化氢（H2O2）、白细胞介素6（IL-6）和血小板衍生生长因子（PDGF）诱导的大鼠系膜细胞（MC）DNA合成中的作用。将MC每天暴露于三次10(-6)mol/L的H2O2脉冲中，单独使用或与IL-6（5 ng/ml）或PDGF（10 ng/ml）联合使用。为了间接检测PG在介导MC DNA合成变化中的作用，将吲哚美辛（1.5×10(-5)mol/L）或血栓素A2合成酶抑制剂达美格雷（10(-5)mol/L）加入培养基中，并在72小时后使用3H-胸腺嘧啶核苷掺入法（3H-TdR）评估DNA合成。单独用H2O2刺激MC导致3H-TdR增加34.7±5.5%（p<0.01）。H2O2增强了IL-6和PDGF的促有丝分裂作用，3H-TdR分别增加52±12.1%（p<0.01）和100±21%（p<0.001）。吲哚美辛抑制了单独由H2O2诱导的DNA合成，3H-TdR降低33±12%（p<0.05）。吲哚美辛还分别将对H2O2加IL-6和H2O2加PDGF的促有丝分裂反应降低了91±17%和97±12%（p<0.05）。当MC单独暴露于H2O2时，达美格雷使3H-TdR降低31.8±16%（p<0.05），当与IL-6或PDGF联合使用时，分别降低80±26%和120±13%（p<0.05）。这些数据表明H2O2诱导的MC生长所介导的途径似乎至少部分涉及PG，尤其是血栓素A2。
