Astragaloside IV ameliorates diabetic nephropathy by modulating the mitochondrial quality control network.
Astragaloside IV ameliorates diabetic nephropathy by modulating the mitochondrial quality control network.
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黄芪甲苷 IV 通过调节线粒体质量控制网络来改善糖尿病肾病。
DOI：
10.1371/journal.pone.0182558
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Li S
中科院分区：
文献类型：
--
作者：
Liu X;Wang W;Song G;Wei X;Zeng Y;Han P;Wang D;Shao M;Wu J;Sun H;Xiong G;Li S
本研究的目的是探讨黄芪甲苷 IV (AS-IV) 在 2 型糖尿病动物模型 db/db 小鼠中延缓糖尿病肾病 (DN) 进展的作用和可能的机制。本研究使用八周大的雄性 db/db 糖尿病小鼠及其非糖尿病同窝对照 db/m 小鼠。通过将 AS-IV 以 1g/kg 的剂量添加到标准饲料中，对 db/db 小鼠施用 AS-IV，持续 12 周。通过尿白蛋白排泄（UAE）和高碘酸希夫染色评估肾损伤。使用蛋白质印迹和免疫组织化学染色分析评估线粒体质量控制相关蛋白的蛋白表达水平。实验结束时，db/db 小鼠表现出明显的肾损伤，表现为UAE增加、尿N-乙酰基-β-D-氨基葡萄糖苷酶（NAG）增加、系膜基质扩张和肾小管面积增加。 AS-IV 给药显着减少了 UAE 和尿 NAG，并改善了 db/db 小鼠中观察到的肾脏病理损伤。此外，db/db 小鼠中线粒体分裂的主要调节因子动力相关蛋白 1 (Drp-1)、线粒体分裂蛋白 1 (Fis-1) 和线粒体分裂因子 (MFF) 的表达显着增加。此外，PTEN 诱导的推定激酶 1 (PINK1)/Parkin 介导的线粒体自噬在 db/db 小鼠中异常激活。 AS-IV 显着降低 db/db 小鼠肾脏 Drp-1、Fis-1 和 MFF 表达，并下调 PINK1/Parkin 介导的线粒体自噬。然而，在我们的研究中，无论是否接受 AS-IV 治疗，db/m 和 db/db 小鼠的线粒体生物发生和线粒体融合相关蛋白水平没有显着差异。总之，给予 AS-IV 可以延缓 2 型糖尿病小鼠的 DN 进展，这可能与线粒体质量控制网络的恢复有关。
The aim of this study was to investigate the effect and possible mechanism of Astragaloside IV (AS-IV) on retarding the progression of diabetic nephropathy (DN) in a type 2 diabetic animal model, db/db mice. Eight-week-old male db/db diabetic mice and their nondiabetic littermate control db/m mice were used in the present study. AS-IV was administered to the db/db mice by adding it to standard feed at a dose of 1g/kg for 12 weeks. Renal injury was assessed by urinary albumin excretion (UAE) and Periodic acid-Schiff staining. The protein expression levels of mitochondrial quality-control-associated proteins were evaluated using Western blotting and immunohistochemical staining analysis. At the end of the experiment, db/db mice showed overt renal injury, as evidenced by increased UAE, increased urinary N-acetyl-β-D-glucosaminidase (NAG), expansion of mesangial matrix, and increased renal tubular area. AS-IV administration significantly reduced UAE and urinary NAG and ameliorated the renal pathologic injury seen in db/db mice. Furthermore, the expression of dynamin-related protein 1 (Drp-1), mitochondrial fission protein 1 (Fis-1), and mitochondrial fission factor (MFF), the main regulators of mitochondrial fission, was significantly increased in db/db mice. Moreover, PTEN-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy was abnormally activated in db/db mice. AS-IV significantly reduced renal Drp-1, Fis-1, and MFF expression and downregulated PINK1/Parkin-mediated mitophagy in db/db mice. However, mitochondrial biogenesis and mitochondrial fusion-associated protein levels were not significantly different between db/m and db/db mice in our study, with or without AS-IV treatment. In conclusion, administration of AS-IV could retard DN progression in type 2 diabetes mice, which might be associated with restoration of the mitochondrial quality control network.
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