Astragaloside IV ameliorates diabetic nephropathy involving protection of podocytes in streptozotocin induced diabetic rats
Astragaloside IV ameliorates diabetic nephropathy involving protection of podocytes in streptozotocin induced diabetic rats
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DOI：
10.1016/j.ejphar.2014.04.037
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发表时间：
2014-08-05
影响因子：
5
通讯作者：
He, Dongyuan
中科院分区：
文献类型：
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作者：
Chen, Jianguo;Chen, Yifang;He, Dongyuan
足细胞的丢失和功能障碍在糖尿病肾病（DN）的发生、发展过程中起着重要作用。本研究旨在观察黄芪甲苷对糖尿病大鼠足细胞的保护作用，并初步探讨其作用机制。将健康雄性SD大鼠随机分为正常对照组、糖尿病肾病组和糖尿病肾病+AS-IV治疗组。腹腔注射链脲佐菌素（STZ）诱导DN。AS-IV治疗在STZ注射前2周开始，持续14周。分别于注射STZ后4、8、12周检测24 h尿蛋白。注射STZ 12周后测量体重、血糖、血尿素氮（BUN）、肌酸酐（Cr）、丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）。采用组织病理学、电镜、免疫组化、western blot和实时荧光定量PCR等方法检测肾组织病理学、足细胞形态学、足细胞密度、整合素α 3、整合素β 1和整合素连接激酶（ILK）的蛋白和mRNA表达。糖尿病大鼠肾组织中ILK蛋白表达增加，整合素α 3和整合素β 1蛋白表达减少，肾小球系膜扩张，足细胞减少。AS-IV治疗可改善足细胞丢失、肾组织病理学和足细胞足突消失，减少蛋白尿，部分恢复整合素α 3、整合素β 1和ILK的蛋白表达。提示AS-Ⅳ可能通过抑制ILK的表达，恢复整合素α 3 β 1的表达，从而保护足细胞，改善糖尿病肾病。(C)2014爱思唯尔有限公司版权所有。
Podocyte loss and dysfunction play key role during the development of diabetic nephropathy (DN). The aim of this study was to observe the protective effects of astragaloside IV on podocyte in diabetic rats and explore its mechanisms preliminary. Healthy male Sprague-Dawley (SD) rats were randomized into normal control group, diabetic nephropathy group and diabetic nephropathy with AS-IV treatment group. DN was induced by intraperitoneal injection of streptozotocin (STZ). AS-IV treatment started 2 weeks before STZ injection and lasted 14 weeks. 24 h Urinary proteins were measured 4, 8 and 12 weeks after STZ injection. Body weight, blood glucose, blood urea nitrogen (BUN), creatinine (Cr), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured 12 weeks after STZ injection. Renal pathology, podocyte morphological changes, podocyte density, protein and mRNA expression of integrin alpha 3, integrin beta 1 and integrin-linked kinase (ILK) were detected by histopathology, electron microscopy, immunohistochemistry, western blot and real-time PCR, respectively. Hyperglycemia, proteinuria, mesangial expansion and podocyte loss, increased protein expression of ILK and decreased protein expression of integrin alpha 3 and integrin beta 1 were detected in diabetic rats. AS-IV treatment ameliorated podocyte loss, renal histopathology and podocyte foot process effacement, decreased proteinuria, partially restored protein expression of integrin alpha 3, integrin beta 1 and ILK. These findings suggested that AS-IV may protect podocyte and ameliorate diabetic nephropathy by inhibiting the expression of ILK and restoring the expression of integrin alpha 3 beta 1 in diabetic rats. (C) 2014 Elsevier B.V. All rights reserved.