Blockade of serotonin 2A receptor improves glomerular endothelial function in rats with streptozotocin-induced diabetic nephropathy
Blockade of serotonin 2A receptor improves glomerular endothelial function in rats with streptozotocin-induced diabetic nephropathy
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DOI：
10.1007/s10157-007-0011-8
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发表时间：
2008-04-01
影响因子：
2.3
通讯作者：
Kashihara, Naoki
中科院分区：
文献类型：
--
作者：
Kobayashi, Shinya;Satoh, Minoru;Kashihara, Naoki
背景5-羟色胺（5-HT）参与血管炎症和动脉粥样硬化的形成。糖尿病患者血清5-HT浓度升高，5-HT参与糖尿病血管病变。盐酸沙格雷酯是一种5-HT 2A受体拮抗剂，具有肾脏保护作用，但其在糖尿病肾病中的作用尚未阐明。本研究的目的是检查沙格雷酯对链脲佐菌素（STZ）诱导的糖尿病大鼠中内皮功能障碍的影响。8周。实验结束时，我们检测了尿白蛋白排泄量、血清脂联素浓度和血小板衍生微粒。通过血小板免疫染色检测肾小球内凝血。通过激光共聚焦显微镜观察肾脏活性氧（ROS）和一氧化氮（NO）的产生，并将其作为肾小球内皮功能障碍的指标。沙格雷酯治疗改善肾小球中ROS/NO失衡，抑制肾小球中血小板聚集，减少血小板衍生微粒，增加血清脂联素水平并降低白蛋白尿水平，结论沙格雷酯可改善STZ糖尿病大鼠的内皮功能。通过减少肾小球血小板活化和增加血清脂联素浓度诱导糖尿病，并表明沙格雷酯可能用于治疗糖尿病肾病
Background Serotonin (5-HT) is involved in vascular inflammation and atherosclerogenesis. Serum 5-HT concentrations are elevated in diabetes, and 5-HT is involved in diabetic vasculopathies. Sarpogrelate hydrochloride, a 5-HT2A receptor antagonist, has renoprotective effects, but its effect in diabetic nephropathy is not elucidated. The aim of this study was to examine the effects of sarpogrelate on endothelial dysfunction in rats with streptozotocin (STZ)induced diabetes.Methods Rats with STZ-induced diabetes were either untreated or treated with sarpogrelate (30 mg/kg P.O.) for 8 weeks. At the end of the experiment, we measured urinary albumin excretion, serum adiponectin concentration and platelet-derived microparticles. Intraglomerular coagulation was detected by immunostaining for platelets. Production of renal reactive oxygen species (ROS) and nitric oxide (NO) was investigated by confocal laser microscopy and used as an index of glomerular endothelial dysfunction.Results Diabetic nephropathy was associated with enhanced production of ROS and diminished bioavailable NO in the glomeruli. Treatment with sarpogrelate improved ROS/NO imbalance in glomeruli, suppressed platelet aggregation in glomeruli, reduced platelet-derived microparticles, increased serum adiponectin level and reduced the level of albuminuria, compared with nontreated diabetic rats.Conclusions Our results indicate that sarpogrelate improves endothelial function in rats with STZ-induced diabetes through a reduction of glomerular platelet activation and an increase in serum adiponectin concentrations and suggest that sarpogrelate is potentially useful for the treatment of diabetic nephropathy.