Paeoniflorin ameliorates Adriamycin-induced nephrotic syndrome through the PPARγ/ANGPTL4 pathway in vivo and vitro
Paeoniflorin ameliorates Adriamycin-induced nephrotic syndrome through the PPARγ/ANGPTL4 pathway in vivo and vitro
复制标题
芍药苷通过体内外 PPAR gamma/ANGPTL4 通路改善阿霉素诱导的肾病综合征
DOI：
10.1016/j.biopha.2017.09.105
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发表时间：
2017-12-01
影响因子：
7.5
通讯作者：
Zhou, Jiuyao
中科院分区：
文献类型：
--
作者：
Lu, Ruirui;Zhou, Jie;Zhou, Jiuyao
芍药苷（Paeoniflorin， PF）是一种从白芍中提取的有效成分，具有防治多种肾脏疾病的作用。然而，PF对肾病综合征（NS）的作用机制尚不清楚。本研究旨在探讨茯苓多糖对阿霉素（ADR）诱导的NS的体内外保护作用及其可能的机制。在动物实验中，PF显著降低NS大鼠24小时尿蛋白、血尿素氮、血清肌酐、总胆固醇和甘油三酯水平，但使总蛋白和白蛋白水平升高。苏木精-伊红（HE）染色显示PF治疗后肾脏病变消失。经PF处理后，大鼠肾组织足细胞形态和数量均恢复正常。PF增加synaptopodin的表达，降低desmin的表达，对足细胞损伤具有保护作用。进一步的研究表明，PF上调肾组织过氧化物酶体增殖物激活受体γ (PPAR γ)，抑制血管生成素样4 （ANGPTL4）。在体外研究中，PF降低了Caspase3和Bax，增加了Bcl-2，表明PF降低了ADR诱导的足细胞凋亡率，并且PF通过上调synaptopodin和降低desmin来改善足细胞损伤。动物实验表明，PF通过激活PPAR γ下调ANGPTL4。然而，GW9662 （PPAR γ抑制剂）可能通过抑制ANGPTL4降解而逆转了PF的治疗效果。总的来说，这些结果表明PF通过激活PPAR γ并随后抑制ANGPTL4对NS具有良好的治疗作用。
Paeoniflorin (PF), an effective composition that is extracted from Radix Paeoniae Alba, plays a role in protecting against various kidney diseases. However, the mechanism of PF on nephrotic syndrome (NS) remains unclear. The aim of this study was to investigate the protective role of PF on Adriamycin (ADR)-induced NS in vivo and vitro as well as its potential mechanism. In animal study, PF significantly decreased the levels of 24-h urine protein, blood urea nitrogen, serum creatinine, total cholesterol and triglycerides in NS rats, but increased the total protein and albumin levels. Hematoxylin-eosin (HE) staining revealed that the kidney lesion was resolved upon PF treatment. After treatment with PF, the morphology and number of podocytes in renal tissue were restored to normal. PF increased expression of synaptopodin and decreased expression of desmin, demonstrating a protective effect in podocyte injury. Further studies revealed that PF upregulated Peroxisome proliferator-activated receptor gamma (PPAR gamma) and restrained Angiopointin-like 4 (ANGPTL4) in kidney tissue. In vitro study, PF reduced Caspase3 and Bax and increased Bcl-2, indicating that the apoptosis rate of podocytes induced by ADR was reduced by PF. Furthermore, PF ameliorated podocyte injury by upregulating synaptopodin and reducing desmin. In accordance with animal study, PF downregulated ANGPTL4 by activating PPAR gamma. However, the therapeutic effects of PF were reversed by GW9662 (PPAR gamma inhibitor), likely by suppressing ANGPTL4 degradation. In general, these results demonstrate that PF has a good therapeutic effect on NS by activating PPAR gamma and subsequently inhibiting ANGPTL4.