Astragaloside IV ameliorates renal injury in streptozotocin-induced diabetic rats through inhibiting NF-κB-mediated inflammatory genes expression
Astragaloside IV ameliorates renal injury in streptozotocin-induced diabetic rats through inhibiting NF-κB-mediated inflammatory genes expression
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DOI：
10.1016/j.cyto.2013.01.008
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发表时间：
2013-03-01
期刊：
影响因子：
3.8
通讯作者：
Wang, Niansong
中科院分区：
文献类型：
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作者：
Gui, Dingkun;Huang, Jianhua;Wang, Niansong
越来越多的证据表明炎症过程参与了糖尿病肾病（DN）的发展。然而，对于糖尿病肾脏的炎症没有有效的干预措施。本研究验证了从黄芪中提取的新型皂苷黄芪甲苷IV（AS-IV）通过抗炎机制改善链脲霉素（STZ）诱导的糖尿病大鼠DN的假设。用STZ （65 mg/kg）腹腔注射诱导大鼠糖尿病。注射STZ 2周后，将大鼠分为3组（每组8只），即糖尿病大鼠、糖尿病大鼠分别给予AS-IV 5、10 mg kg(-1) d(-1), p.o.，连续8周。取正常大鼠作为非糖尿病对照组（n = 8）。诱导糖尿病后10周处死大鼠。AS-IV改善糖尿病大鼠蛋白尿、肾组织病理学和足细胞足突消退。糖尿病肾脏NF-kappa B活性、蛋白和mRNA表达升高，肾脏组织中tnf - α、MCP-1和ICAM-1 mRNA表达和蛋白含量升高。糖尿病大鼠肾脏α(1)链IV型胶原mRNA表达升高。所有这些异常均通过AS-IV得到部分恢复。AS-IV还能降低糖尿病大鼠血清中tnf - α、MCP-1和ICAM-1的水平。上述结果提示AS-IV是一种新型抗炎药，通过抑制NE-kappa B介导的炎症基因表达来减轻大鼠DN。(C) 2013 Elsevier Ltd.版权所有。
Accumulating evidence suggests that inflammatory processes are involved in the development of diabetic nephropathy (DN). However, there are no effective interventions for inflammation in the diabetic kidneys. Here, we tested the hypothesis that Astragaloside IV(AS-IV), a novel saponin purified from Astragalus membranaceus (Fisch) Bge, ameliorates DN in streptozotocin (STZ)-induced diabetic rats through anti-inflammatory mechanisms. Diabetes was induced with STZ (65 mg/kg) by intraperitoneal injection in rats. Two weeks after STZ injection, rats were divided into three groups (n = 8/each group), namely, diabetic rats, diabetic rats treated with AS-IV at 5 and 10 mg kg(-1) d(-1), p.o., for 8 weeks. The normal rats were chosen as nondiabetic control group (n = 8). The rats were sacrificed 10 weeks after induction of diabetes. AS-IV ameliorated albuminuria, renal histopathology and podocyte foot process effacement in diabetic rats. Renal NF-kappa B activity, as wells as protein and mRNA expression were increased in diabetic kidneys, accompanied by an increase in mRNA expression and protein content of TNF-alpha, MCP-1 and ICAM-1 in kidney tissues. The alpha(1)-chain type IV collagen mRNA was elevated in the kidneys of diabetic rats. All of these abnormalities were partially restored by AS-IV. AS-IV also decreased the serum levels of TNF-alpha, MCP-1 and ICAM-1 in diabetic rats. These findings suggest that AS-IV, a novel anti-inflammatory agent, attenuated DN in rats through inhibiting NE-kappa B mediated inflammatory genes expression. (C) 2013 Elsevier Ltd. All rights reserved.