Methotrexate prevents renal injury in experimental diabetic rats via anti-inflammatory actions.
Methotrexate prevents renal injury in experimental diabetic rats via anti-inflammatory actions.
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DOI：
10.1681/asn.2004111011
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发表时间：
2005-11
期刊：
影响因子：
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通讯作者：
Kosuke Yozai;K. Shikata;Motofumi Sasaki;A. Tone;S. Ohga;H. Usui;S. Okada;J. Wada;Ryo Nagase-Ryo-Nagas
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文献类型：
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作者：
Kosuke Yozai;K. Shikata;Motofumi Sasaki;A. Tone;S. Ohga;H. Usui;S. Okada;J. Wada;Ryo Nagase-Ryo-Nagas
近年来的研究表明，炎症过程参与了糖尿病肾病的发病机制。甲氨蝶呤（MTX）是一种叶酸拮抗剂，广泛用于治疗炎症性疾病。最近，已经显示用低剂量MTX治疗降低了类风湿性关节炎患者的心血管死亡率，表明MTX通过其抗炎作用具有抗动脉粥样硬化作用。本研究旨在确定该药物对糖尿病肾病的抗炎作用。用链脲佐菌素诱导SD大鼠糖尿病模型，MTX（0.5或1.0mg/kg）每周给药1次，共8 wk。MTX治疗减少尿白蛋白排泄，系膜基质扩张，巨噬细胞浸润，TGF-β和IV型胶原蛋白的表达，以及肾小球细胞间粘附分子-1。MTX在体外和体内也能降低高糖诱导的NF-κ B活化。结果表明，MTX间歇给药可预防实验性糖尿病大鼠的肾损伤，而不影响血糖和血压。MTX的保护作用被认为是通过其抗炎作用介导的，其抗炎作用通过抑制NF-κ B活化和随后的细胞间粘附分子-1表达和巨噬细胞浸润的减少。结果表明，抗炎药可能是有益的治疗糖尿病肾病。
Recent studies suggested the involvement of inflammatory processes in the pathogenesis of diabetic nephropathy. Methotrexate (MTX), a folic acid antagonist, is widely used for the treatment of inflammatory diseases. Recently, it has been shown that treatment with low-dose MTX reduces the cardiovascular mortality in patients with rheumatoid arthritis, suggesting that MTX has anti-atherosclerotic effects via its anti-inflammatory actions. This study was designed to determine the anti-inflammatory effects of this agent on diabetic nephropathy. Diabetes was induced in Sprague-Dawley rats with streptozotocin, and MTX (0.5 or 1.0 mg/kg) was administered once a week for 8 wk. Treatment with MTX reduced urinary albumin excretion, mesangial matrix expansion, macrophage infiltration, expression of TGF-beta and type IV collagen, and intercellular adhesion molecule-1 in glomeruli. MTX also reduced the high glucose-induced NF-kappaB activation in vitro and in vivo. The results indicate that intermittent administration of MTX prevented renal injuries without changes in blood glucose level and BP in experimental diabetic rats. The protective effects of MTX are suggested to be mediated by its anti-inflammatory actions through inhibition of NF-kappaB activation and consequent reduction of intercellular adhesion molecule-1 expression and macrophage infiltration. The results suggest that anti-inflammatory agents might be beneficial for the treatment of diabetic nephropathy.