Takebayashi Kohzo, Matsumoto Sachiko, Aso Yoshimasa, Inukai Toshihiko
Department of Internal Medicine, Koshigaya Hospital, Dokkyo University School of Medicine, 2-1-50, Minami-Koshigaya, Koshigaya 343-8555, Japan.
J Clin Endocrinol Metab. 2006 Jun;91(6):2214-7. doi: 10.1210/jc.2005-1718. Epub 2006 Mar 28.
Aldosterone causes organic impairment by enhancement of oxidative stress and subsequent induction of proinflammatory cytokines and chemokines.
This study was designed to investigate the effect of spironolactone, an aldosterone blocker, on oxidative stress and the level of urinary monocyte chemoattractant protein (MCP)-1, a cysteine-cysteine chemokine that may contribute to progression of various nephropathies in type 2 diabetic patients with diabetic nephropathy. DESIGN, SETTING, PATIENTS AND OTHER PARTICIPANTS, AND INTERVENTION: The patients were randomly assigned to two groups in which they received either spironolactone (50 mg/d; n = 23) or amlodipine (2.5 mg/d; n = 14).
Urinary 8-iso-prostaglandin (PG) F2alpha (a marker of oxidative stress), urinary MCP-1, and urinary albumin excretion (UAE) were measured at the start of administration (0 months) and after 3 months in each group. Baseline levels of these variables were also measured in 25 age-matched healthy subjects.
There were significant positive correlations between log(10)-transformed (log) 8-iso-PGF2alpha and log MCP-1 levels in control and diabetic subjects and all subjects combined, but no correlations between log UAE and log 8-iso-PGF2alpha or log MCP-1 were found in any group. Significant decreases in 8-iso-PGF2alpha, MCP-1, and UAE were observed with spironolactone (P = 0.0001, P = 0.0041, and P = 0.0037, respectively), and systolic blood pressure significantly decreased after both spironolactone and amlodipine therapy (P = 0.00011 and P = 0.0051, respectively).
Our data suggest that urinary MCP-1 is correlated with oxidative stress as measured by urinary 8-iso-PGF2alpha and that spironolactone can decrease urinary MCP-1 and oxidative stress.
醛固酮通过增强氧化应激以及随后诱导促炎细胞因子和趋化因子导致器官损伤。
本研究旨在探讨醛固酮阻滞剂螺内酯对氧化应激以及尿单核细胞趋化蛋白（MCP）-1水平的影响，MCP-1是一种半胱氨酸-半胱氨酸趋化因子，可能在2型糖尿病肾病患者的各种肾病进展中起作用。设计、地点、患者及其他参与者和干预措施：患者被随机分为两组，分别接受螺内酯（50mg/d；n = 23）或氨氯地平（2.5mg/d；n = 14）治疗。
在给药开始时（0个月）和3个月后，测量每组患者的尿8-异前列腺素（PG）F2α（氧化应激标志物）、尿MCP-1和尿白蛋白排泄量（UAE）。还测量了25名年龄匹配的健康受试者这些变量的基线水平。
在对照组、糖尿病组以及所有受试者中，经对数（10）转换后的（log）8-异前列腺素F2α与log MCP-1水平之间存在显著正相关，但在任何组中均未发现log UAE与log 8-异前列腺素F2α或log MCP-1之间存在相关性。螺内酯治疗后，8-异前列腺素F2α、MCP-1和UAE均显著降低（分别为P = 0.0001、P = 0.0041和P = 0.0037），螺内酯和氨氯地平治疗后收缩压均显著降低（分别为P = 0.00011和P = 0.0051）。
我们的数据表明，尿MCP-1与通过尿8-异前列腺素F2α测量的氧化应激相关，且螺内酯可降低尿MCP-1和氧化应激。
