Ogawa Susumu, Mori Takefumi, Nako Kazuhiro, Ishizuka Tsuneo, Ito Sadayoshi
Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai 980-8574, Japan.
Clin J Am Soc Nephrol. 2008 Mar;3(2):362-8. doi: 10.2215/CJN.03450807. Epub 2008 Jan 30.
Sarpogrelate has been shown to reduce albuminuria in diabetic nephropathy. For examination of whether this is based on the same mechanisms as angiotensin II receptor blockers or thiazolidinedione, effects of sarpogrelate on atherosclerotic inflammatory molecules and their relations to albuminuria in patients who had diabetes and had already been treated with angiotensin II receptor blockers and with or without thiazolidinedione were examined.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Forty patients who had diabetes with nephropathy and arteriosclerosis obliterans and had already been treated with angiotensin II receptor blocker (n = 40) were randomly assigned to sarpogrelate (300 mg/d; n = 20) or aspirin group (100 mg/d; n = 20). Plasma monocyte chemoattractant protein-1 and urinary albumin-to-creatinine ratio and monocyte chemoattractant protein-1 were measured at baseline and 16 wk after administration.
Only the sarpogrelate group showed increases in plasma adiponectin and decreases in both plasma and urinary monocyte chemoattractant protein-1 and albumin-to-creatinine ratio levels. Moreover, percentage change of monocyte chemoattractant protein-1 level correlated positively to that of albumin-to-creatinine ratio. Even when the sarpogrelate group was further divided into two groups with (n = 9) or without thiazolidinedione (n = 11), changes in monocyte chemoattractant protein-1 or albumin-to-creatinine ratio did not differ.
Sarpogrelate can reduce albuminuria and plasma and urinary monocyte chemoattractant protein-1 levels while increasing plasma adiponectin in diabetic nephropathy. These effects seem to be mediated via mechanisms that are different from those of angiotensin II receptor blocker or thiazolidinedione.
已证实沙格雷酯可减少糖尿病肾病患者的蛋白尿。为研究其作用机制是否与血管紧张素II受体阻滞剂或噻唑烷二酮类相同,我们对已接受血管紧张素II受体阻滞剂治疗且使用或未使用噻唑烷二酮类药物的糖尿病患者,检测了沙格雷酯对动脉粥样硬化炎症分子的影响及其与蛋白尿的关系。
设计、地点、参与者及测量方法:40例患有糖尿病肾病和闭塞性动脉硬化且已接受血管紧张素II受体阻滞剂治疗的患者(n = 40),被随机分为沙格雷酯组(300 mg/d;n = 20)或阿司匹林组(100 mg/d;n = 20)。在基线及给药16周后测量血浆单核细胞趋化蛋白-1、尿白蛋白与肌酐比值以及单核细胞趋化蛋白-1。
仅沙格雷酯组血浆脂联素增加,血浆和尿液单核细胞趋化蛋白-1及白蛋白与肌酐比值水平降低。此外,单核细胞趋化蛋白-1水平的百分比变化与白蛋白与肌酐比值的百分比变化呈正相关。即使将沙格雷酯组进一步分为使用(n = 9)或未使用噻唑烷二酮类药物(n = 11)的两组,单核细胞趋化蛋白-1或白蛋白与肌酐比值的变化并无差异。
在糖尿病肾病中,沙格雷酯可降低蛋白尿、血浆和尿液单核细胞趋化蛋白-1水平,同时增加血浆脂联素。这些作用似乎是通过与血管紧张素II受体阻滞剂或噻唑烷二酮类不同的机制介导的。