Resveratrol Attenuates Early Diabetic Nephropathy by Down-Regulating Glutathione S-Transferases Mu in Diabetic Rats
Resveratrol Attenuates Early Diabetic Nephropathy by Down-Regulating Glutathione S-Transferases Mu in Diabetic Rats
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DOI：
10.1089/jmf.2012.2686
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发表时间：
2013-06-01
影响因子：
2.4
通讯作者：
Gao, Hai-Qing
中科院分区：
文献类型：
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作者：
Jiang, Bei;Guo, Ling;Gao, Hai-Qing
糖尿病肾病（DN）是终末期肾病的主要原因。白藜芦醇已被证明可以改善糖尿病大鼠的高血糖症。然而，白藜芦醇对 DN 的影响仍不清楚。本研究的目的是探讨白藜芦醇对早期 DN 的影响。雄性 Wistar 大鼠通过注射链脲佐菌素诱发糖尿病。糖尿病大鼠接受白藜芦醇治疗，剂量为20毫克/公斤体重，持续8周。测定血浆葡萄糖、肌酐、肾/体重比和24小时尿蛋白。用高碘酸希夫染色检查肾脏病理变化，并在指定浓度的白藜芦醇（2.5、5.0和10.0μmol/L）的高葡萄糖浓度下培养肾系膜细胞。通过甲基噻唑四唑测定评估系膜细胞的增殖。采用蛋白质印迹法检测谷胱甘肽S-转移酶Mu（GSTM）和核因子红细胞2相关因子2（Nrf2）的表达，并使用流式细胞仪分析细胞凋亡。白藜芦醇减少血浆葡萄糖、肌酐和尿蛋白排泄，并减轻肾脏肥大。此外，白藜芦醇还降低糖尿病大鼠中GSTM的表达。在体外，白藜芦醇可抑制高糖引起的系膜细胞增殖，并以剂量依赖性方式下调 GSTM 和 Nrf2 表达。这些发现表明白藜芦醇有助于预防 DN 的进展。白藜芦醇的肾脏保护作用部分是通过抑制高糖诱导的大鼠系膜细胞增殖和下调 GSTM 表达来介导的。
Diabetic nephropathy (DN) is the major cause of end-stage renal disease. Resveratrol has been shown to ameliorate hyperglycemia in diabetic rats. However, the effects of resveratrol on DN remain unknown. The aim of the present study is to investigate the effects of resveratrol on early-stage DN. Diabetes was induced by streptozotocin injection in male Wistar rats. The diabetic rats were treated with resveratrol at a dose of 20 mg/kg body weight for 8 weeks. Plasma glucose, creatinine, kidney/body weight ratio, and 24-h urinary protein were determined. The renal pathological changes were examined with periodic acid Schiff staining, and renal mesangial cells were cultured in high glucose concentrations with indicated concentrations of resveratrol (2.5, 5.0, and 10.0 mu mol/L). The proliferation of mesangial cells was evaluated by methylthiazoletetrazolium assay. Expressions of glutathione S-transferases Mu (GSTM) and nuclear factor erythroid 2-related factor 2 (Nrf2) were detected by western blot, and apoptosis was analyzed using a flow cytometer. Resveratrol reduced plasma glucose, creatinine, and urinary protein excretion, and attenuated renal hypertrophy. Moreover, resveratrol also reduced the expression of GSTM in diabetic rats. In vitro, resveratrol inhibited the proliferation of mesangial cells caused by high glucose and down-regulated GSTM and Nrf2 expressions in a dose-dependent manner. These findings suggest that resveratrol help prevent the progression of DN. The renoprotection by resveratrol is in part mediated through the inhibition of high glucose-induced rat mesangial cell proliferation and downregulation of GSTM expression.