Protective effect of astragalosides from Radix Astragali on adriamycin-induced podocyte injury
Protective effect of astragalosides from Radix Astragali on adriamycin-induced podocyte injury
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DOI：
10.3892/etm.2018.5933
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发表时间：
2018-05
影响因子：
2.7
通讯作者：
Y. Sai;Yuan Song;Xing-Xing Chen-Xing;Xuan Luo;Jing Liu;Weijing Cui
中科院分区：
文献类型：
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作者：
Y. Sai;Yuan Song;Xing-Xing Chen-Xing;Xuan Luo;Jing Liu;Weijing Cui
肾病综合征（NS）是临床上最常见的肾脏疾病，可导致终末期肾功能衰竭。黄芪甲苷（AST）已被临床试验用于治疗NS，但其作用机制仍有待阐明。本研究旨在探讨AST对阿霉素（ADR）损伤足细胞结构和功能的影响，并阐明其分子机制。小鼠足细胞克隆5（MPC 5）永生化小鼠足细胞系用0.5 µmol/l ADR处理以建立足细胞损伤模型。将MPC 5足细胞分为对照组、足细胞损伤组和低、中、高浓度AST处理组。结果表明，足细胞损伤组小鼠的存活率明显低于对照组，AST各处理组小鼠的存活率均高于足细胞损伤组。AST各剂量组均可显著抑制ADR引起的MPC 5足细胞乳酸脱氢酶和丙二醛水平的升高及超氧化物歧化酶活性的降低。此外，AST提高了MPC 5足细胞的迁移能力，并抑制了与ADR诱导的损伤相关的细胞骨架重排。足细胞损伤组基质金属蛋白酶（MMP）-2和MMP-9表达降低，不同浓度的AST可抑制MMP-2和MMP-9表达。因此，AST能够维持ADR培养的足细胞氧化应激的平衡，并保护它们免受ADR诱导的损伤。其机制可能与MMPs表达上调有关。
Nephrotic syndrome (NS) is the most common kidney disease in clinical practice and may lead to end-stage renal failure. Astragalosides (AST) have been clinically tested for the treatment of NS, but their mechanism of action has remained to be elucidated. The aim of the present study was to investigate the effect of AST on the structure and function of podocytes with adriamycin (ADR)-induced damage and to elucidate the underlying molecular mechanisms. The mouse podocyte clone 5 (MPC5) immortalized mouse podocyte cell line was treated with 0.5 µmol/l ADR to establish a podocyte injury model. The MPC5 podocytes were divided into a control group, a podocyte injury group and a low-, medium- and high-concentration AST treatment group. The results indicated that the survival rate of the podocyte injury group was significantly decreased compared with that in the control group and each AST-treated group had an increased survival rate compared with that in the podocyte injury group. Furthermore, each dose of AST significantly inhibited the ADR-associated increases the levels of lactate dehydrogenase and malondialdehyde and the decrease in the activity of superoxide dismutase in MPC5 podocytes. In addition, AST improved the migration ability of MPC5 podocytes and suppressed the cytoskeletal rearrangement associated with ADR-induced damage. Furthermore, matrix metalloproteinase (MMP)-2 and -9 were decreased in the podocyte injury group, which was inhibited by different concentrations of AST. Thus, AST was able to maintain the balance of oxidative stress in podocytes cultured with ADR and protect them from ADR-induced injury. The mechanism may be associated with the upregulation of MMPs.