Combination Therapy with Paricalcitol and Enalapril Ameliorates Cardiac Oxidative Injury in Uremic Rats
Combination Therapy with Paricalcitol and Enalapril Ameliorates Cardiac Oxidative Injury in Uremic Rats
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DOI：
10.1159/000178251
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发表时间：
2009-01-01
影响因子：
4.2
通讯作者：
Slatopolsky, Eduardo
中科院分区：
文献类型：
--
作者：
Husain, Kazim;Ferder, Leon;Slatopolsky, Eduardo
目的：本研究探讨了血管紧张素转换酶抑制剂依那普利和维生素D类似物帕立骨化醇单独或联合给药对尿毒症大鼠心脏氧化应激的保护作用。研究方法：通过5/6肾切除术制备大鼠尿毒症模型，并按以下方法治疗4个月：（1）尿毒症+溶媒（n = 11）;（2）尿毒症+依那普利（n = 11）;（饮用水中30 mg/l，n = 13）;（3）尿毒症+帕立骨化醇（200 ng 3 X周，n = 6）;（4）尿毒症+依那普利+帕立骨化醇（n = 14），和（5）对照（n = 6）。结果：尿毒症大鼠心肌NADPH氧化酶活性较正常对照组升高300%。依那普利、帕立骨化醇或两者联合治疗可通过抑制酶活性保护尿毒症大鼠免受心脏氧化应激。与正常对照组相比，尿毒症大鼠心脏丙二醛（MDA）水平显著升高。只有联合治疗抑制尿毒症大鼠MDA水平的增加。与正常对照组相比，尿毒症大鼠心脏谷胱甘肽显著减少。依那普利、帕立骨化醇或两者联合使用均可防止谷胱甘肽的这种还原。尿毒症大鼠心肌铜锌超氧化物歧化酶（CuZn-SOD）活性降低，锰（Mn-SOD）活性升高。单药和联合治疗均能改善尿毒症大鼠心脏SOD活性的改变。结论：依那普利、帕立骨化醇及其联合治疗对尿毒症患者心脏氧化应激具有保护作用。版权所有（c）2008 S. Karger AG，巴塞尔
Aims: This study investigated the protective effect of the angiotensin-converting enzyme inhibitor, enalapril, and the vitamin D analog, paricalcitol, alone or in combination, on cardiac oxidative stress in uremic rats. Methods: Rats were made uremic by 5/6 nephrectomy and treated for 4 months as follows: (1) uremic + vehicle (n = 11); (2) uremic + enalapril (30 mg/l in drinking water, n = 13); (3) uremic + paricalcitol (200 ng 3X week, n = 6); (4) uremic + enalapril + paricalcitol (n = 14), and (5) controls (n = 6). Results: Cardiac NADPH oxidase activity increased by 300% in uremic rats compared to normal controls. Treatment with enalapril, paricalcitol or the combination of the two protected uremic rats from cardiac oxidative stress by inhibiting enzyme activity. Cardiac malondialdehyde (MDA) levels were significantly increased in uremic rats compared to normal controls. Only the combination therapy inhibited the increase in MDA levels in uremic rats. Cardiac glutathione was significantly reduced in uremic rats compared to normal controls. Enalapril, paricalcitol or the two in combination all protected against this reduction in glutathione. Cardiac copper/zinc superoxide dismutase (CuZn-SOD) activity decreased whereas manganese (Mn-SOD) activity increased in uremic rats compared to controls. Both mono and combination therapies ameliorated the alterations in cardiac SOD activity seen in uremic rats. Conclusion: Enalapril, paricalcitol and their combined therapy afford protection against cardiac oxidative stress in uremia. Copyright (c) 2008 S. Karger AG, Basel