Proinflammatory effects of oxidative stress in chronic kidney disease: role of additional angiotensin II blockade
Proinflammatory effects of oxidative stress in chronic kidney disease: role of additional angiotensin II blockade
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DOI：
10.1152/ajprenal.00385.2002
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发表时间：
2003-04-01
影响因子：
4.2
通讯作者：
Agarwal, R
中科院分区：
文献类型：
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作者：
Agarwal, R
氧化应激在慢性进行性肾脏病(CKD)的发病中起着重要作用。我们观察了加用血管紧张素Ⅱ受体阻滞剂氯沙坦(50 mg/天，1个月)对慢性肾脏病患者肾脏氧化应激和促炎状态的影响。所有受试者都服用血管紧张素转换酶抑制剂和其他抗高血压药物。用高效液相色谱法测定脂质和蛋白质的氧化应激，分别测定丙二醛(MDA)和羰基浓度。用单核细胞趋化蛋白-1(MCP-1)排泄率测定尿液炎症反应。CKD的病因为2型糖尿病12例，肾小球肾炎4例。加用血管紧张素Ⅱ受体阻滞剂氯沙坦治疗后，蛋白尿和24小时动态血压无明显变化。氯沙坦治疗前尿蛋白和白蛋白氧化值分别比血浆高99%和71%(P<；0.05)。加用氯沙坦治疗后，尿氧化白蛋白降低了35%(P=0.036)。与年龄匹配的对照组相比，尿和血浆中的丙二醛水平升高。加用氯沙坦治疗后，尿丙二醛从4.75+/-3.23降至3.39/-2.17 mU/m o l/g肌酐。然而，血浆丙二醛或氧化蛋白没有改变对额外的血管紧张素Ⅱ阻滞剂的反应。尿氧化白蛋白变化与单核细胞趋化蛋白-1水平呈正相关(r=0.61，P=0.012)。这些数据表明，增加Ang II受体阻滞剂可以减少对尿蛋白和血脂的氧化损伤，而不影响蛋白尿或血压的降低。在慢性肾脏病患者中，尿液检测脂质和蛋白质氧化损伤的标志物似乎比血浆检测更敏感。尿单核细胞趋化蛋白-1的变化与氧化应激的减少之间的显著关联支持了氧化还原状态在肾脏纤维化和进行性肾损害中的作用。
Oxidative stress plays an important role in causing progressive chronic kidney disease (CKD). We examined the influence of add-on ANG II receptor blockade administered as losartan (50 mg/day for 1 mo) on oxidative stress and proinflammatory state of the kidney in patients with CKD. All subjects were taking an angiotensin-converting enzyme inhibitor plus other antihypertensive agents. Oxidative stress to lipids and proteins was measured by an HPLC assay for malondialdehyde (MDA) and carbonyl concentration, respectively. Urinary inflammation was measured by monocyte chemotactic protein-1 (MCP-1) excretion rate. The etiology of CKD was type 2 diabetes mellitus in 12 and glomerulonephritis in 4 patients. There was no change in proteinuria or 24-h ambulatory blood pressure (BP) with add-on ANG II receptor blockade with losartan therapy. Before losartan therapy, urinary protein and albumin oxidation were 99 and 71% higher, respectively, compared with in plasma (P < 0.05). There was a 35% reduction in urinary oxidized albumin with add-on losartan therapy (P = 0.036). Urinary and plasma MDA were elevated compared with age-matched controls. Urinary MDA was significantly reduced from 4.75 +/- 3.23 to 3.39 +/- 2.17 mu mol/g creatinine with add-on losartan therapy. However, plasma MDA or oxidized proteins did not change in response to additional ANG II blockade. A good correlation was seen between the change in urinary oxidized albumin and MCP-1 levels (r = 0.61, P = 0.012). These data demonstrate that oxidative damage to urinary protein and lipids can be reduced with additional ANG II receptor blockade, independently of reductions in proteinuria or BP. Urinary measurements of markers of oxidative damage to lipids and proteins appear to be more sensitive than plasma measurements in patients with CKD. The significant association of the change in urinary MCP-1 with a reduction in oxidative stress supports the role of the redox state in the kidney with renal fibrosis and progressive kidney damage.