Protective Effects of the Total Coumarin Fraction of Urtica dentata on Experimental Diabetic Nephropathy In Vitro and In Vivo

Protective Effects of the Total Coumarin Fraction of Urtica dentata on Experimental Diabetic Nephropathy In Vitro and In Vivo
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荨麻总香豆素部位对实验性糖尿病肾病体外和体内的保护作用

DOI:
10.1055/s-0035-1557866
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发表时间:
2015-10-01
期刊:
影响因子:
2.7
通讯作者:
Xiang, Ming
Xiang, Ming
中科院分区:
医学3区
文献类型:
--
作者:
Cao, Hui;Ji, Yachun;Xiang, Ming

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摘要 我们之前报道过,总香豆素是荨麻的主要活性成分,对自身免疫性糖尿病的发展具有显着的保护作用。糖尿病肾病是糖尿病最严重的并发症之一,与终末期肾病密切相关。我们使用大鼠肾小球系膜细胞系(HBZY-1)和链脲佐菌素诱导的糖尿病大鼠来研究总香豆素对糖尿病肾病的潜在保护作用和机制。我们的数据显示,总香豆素抑制高葡萄糖诱导的 HBZY-1 细胞增殖和肥大,并通过下调转化生长因子-β1、结缔组织生长因子和 Toll 样受体 4 的激活来发挥作用。与这些发现一致的是,在糖尿病模型中施用总香豆素具有体内抗肾损伤作用。总香豆素,剂量为 50 或 100mg/kg 时: 1) 体重显着增加; 2)改善肾脏病理学的形态学证据; 3)降低血液中葡萄糖和尿素氮水平; 4) 降低蛋白尿和血清肌酐; 5) 肾脏中转化生长因子-β1、结缔组织生长因子和 Toll 样受体 4 的蛋白质和基因水平降低。这些结果支持这样的观点,即总香豆素治疗对 DN 具有显着的肾脏保护作用。
Abstract We previously reported that total coumarins, the major active components of Urtica dentata Hand, exhibited substantial protection against the development of autoimmune diabetes. Diabetic nephropathy is one of the most serious complications of diabetes and is closely correlated with end-stage renal disease. We used the rat glomerular mesangial cell line (HBZY-1) and streptozotocin-induced diabetic rats to investigate the potential protective effects and mechanisms of total coumarins on diabetic renal disease. Our data revealed that total coumarins inhibited high glucose-induced HBZY-1 cell proliferation and hypertrophy, and produced its effects through downregulating transforming growth factor-β1, connective tissue growth factor, and toll-like receptor 4 activation. Consistent with those findings, total coumarins administration in a diabetic model had anti-renal lesion effects in vivo. Total coumarins, at a dose of 50 or 100 mg/kg: 1) significantly increased body weight; 2) ameliorated morphological evidence of renal pathology; 3) decreased blood levels of glucose and urea nitrogen; 4) decreased albuminuria and serum creatinine; and 5) reduced protein and gene levels of transforming growth factor-β1, connective tissue growth factor, and toll-like receptor 4 in the kidneys. These results support the view that total coumarins treatment can be substantially renoprotective in DN.