Grape Seed Proanthocyanidins Ameliorate Diabetic Nephropathy via Modulation of Levels of AGE, RAGE and CTGF
Grape Seed Proanthocyanidins Ameliorate Diabetic Nephropathy via Modulation of Levels of AGE, RAGE and CTGF
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DOI：
10.1159/000191103
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发表时间：
2009-01-01
影响因子：
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通讯作者：
Ma, Yabing
中科院分区：
文献类型：
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作者：
Li, Xianhua;Xiao, Yunling;Ma, Yabing
背景：糖尿病肾病是终末期肾功能衰竭最常见的原因。葡萄籽原花青素提取物(GSPE)是一种强大的抗氧化剂。然而，GSPE在糖尿病肾病中对晚期糖基化终产物(AGEs)、晚期糖基化终产物受体(RAGE)和结缔组织生长因子(CTGF)表达的影响尚不清楚。在链脲佐菌素诱导的糖尿病大鼠模型上，我们评价了GSPE对糖尿病肾病的影响。方法：用链脲佐菌素诱导Wistar大鼠糖尿病模型，给予GSPE 500 mg·kg~(-1)·d~(-1)治疗24周。用PAS染色和电子显微镜观察肾脏病理变化。RT-PCR、Western印迹和免疫组织化学染色检测肾组织RAGE和CTGF的mRNA和蛋白表达。结果：用药组动物血清AGEs(p<；0.01)、蛋白尿(p<；0.01)和收缩压(p<；0.01)均显著降低。GSPE可降低肾组织RAGE(p<；0.01)和CTGF(p<；0.01)的表达，从而逆转糖尿病肾病细胞外基质积聚。结论：我们的结果表明GSPE在治疗糖尿病肾病方面有很大的前景。GSPE可减少蛋白尿，延缓糖尿病大鼠肾病的进展。GSPE的肾脏保护作用与其抑制AGEs/RAGE轴、下调CTGF的表达有关。版权所有(C)2009 S.Karger AG，巴塞尔
Background: Diabetic nephropathy (DN) is the most common cause of end-stage renal failure. Grape seed proanthocyanidin extracts (GSPE) are powerful antioxidants. However, the role of GSPE on advanced glycation end products (AGEs), receptor for advanced glycation end products (RAGE) and expression of connective tissue growth factor (CTGF) in DN has not been elucidated. Using streptozotocin-induced diabetic rats, we evaluated the effects of GSPE in DN. Methods: Wistar rats were induced into diabetes using streptozotocin injections and diabetic rats were treated with GSPE (dosage: 500 mg.kg(-1).day(-1)) for 24 weeks. The renal pathological changes were examined with PAS staining and electron microscope. The mRNA and protein expression of RAGE and CTGF in kidney were detected by RT-PCR, Western blot and immunohistochemical staining. Results: Treated animals showed reduction in serum AGEs (p < 0.01), proteinuria (p < 0.01) and systolic blood pressure (p < 0.01). GSPE reduced the expression of RAGE (p < 0.01) and CTGF (p < 0.01) in the kidney, which were contributing to reversal of extracellular matrix accumulation in DN. Conclusion: Our results suggest that GSPE hold substantial promise for the treatment of DN. GSPE can decrease proteinuria, attenuating the progression of nephropathy in diabetic rats. Renoprotective effects of GSPE are correlated with suppression on AGEs/RAGE axis, downregulating expression of CTGF. Copyright (C) 2009 S. Karger AG, Basel