Salidroside stimulates the Sirt1/PGC-1α axis and ameliorates diabetic nephropathy in mice

Salidroside stimulates the Sirt1/PGC-1α axis and ameliorates diabetic nephropathy in mice
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红景天苷刺激 Sirt1/PGC-1 α 轴并改善小鼠糖尿病肾病

DOI:
10.1016/j.phymed.2018.10.031
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发表时间:
2019-02-15
期刊:
影响因子:
7.9
通讯作者:
Sun, Cheng
Sun, Cheng
中科院分区:
医学1区
文献类型:
--
作者:
Xue, Haiyan;Li, Peipei;Sun, Cheng

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背景:红景天苷是中药红景天的活性成分,具有抗炎、抗癌、抗氧化等多种药理作用。然而,红景天苷在糖尿病肾病中是否发挥有益作用尚不清楚。目的:本研究的目的是探讨红景天苷抗糖尿病肾病的潜在作用及其潜在的分子机制。方法:给予肥胖小鼠链脲佐菌素建立糖尿病肾病动物模型。给这些小鼠注射红景天苷,并检查蛋白尿、足细胞完整性、肾脏形态和纤维化、线粒体生物发生。结果:我们的结果表明,红景天苷治疗可大大减轻糖尿病肾病,尿白蛋白、血尿素氮和血清肌酐的降低就证明了这一点。形态学分析表明红景天苷可改善糖尿病肾病的肾脏结构。红景天苷显着逆转了去氧肾上腺素和足多蛋白表达的降低。此外,红景天苷在很大程度上预防了糖尿病肾病小鼠的肾纤维化。从机制上讲,在红景天苷治疗的小鼠中,线粒体 DNA 拷贝和电子传递链蛋白显着增强。同时,红景天苷的存在几乎完全抵消了糖尿病肾病中减少的 Sirt1 和 PGC-1 α 表达。结论:我们的数据表明,红景天苷对小鼠糖尿病肾病发挥有益作用,这可能是通过 Sirt1/PGC-1 α 介导的线粒体生物合成。
Background: Salidroside, an active component from Traditional Chinese Medicine Rhodiola rosea L., has various pharmacological functions including anti-inflammatory, anti-cancer and anti-oxidative properties. However, whether salidroside plays a beneficial role in diabetic nephropathy is still unclear.Purpose: The objective of this work was to investigate the potential roles of salidroside against diabetic nephropathy and the underlying molecular mechanisms.Methods: Streptozocin was given to obese mice to generate diabetic nephropathy animal model. Salidroside was administered to these mice and proteinuria, podocyte integrity, renal morphology and fibrosis, mitochondrial biogenesis were examined.Results: Our results showed that salidroside treatment greatly attenuates diabetic nephropathy as evidenced by decreased urinary albumin, blood urea nitrogen and serum creatinine. Morphological analysis indicated that salidroside improves renal structures in diabetic nephropathy. The decreases in nephrin and podocin expression were markedly reversed by salidroside. Moreover, kidney fibrosis in diabetic nephropathy mice was largely prevented by salidroside. Mechanistically, in salidroside-treated mice, the mitochondrial DNA copy and electron transport chain proteins were significantly enhanced. Meanwhile, the reduced Sirt1 and PGC-1 alpha expression in diabetic nephropathy was almost completely counteracted in the presence of salidroside.Conclusions: Our data showed that salidroside plays a beneficial role against diabetic nephropathy in mice, which probably via Sirt1/PGC-1 alpha mediated mitochondrial biogenesis.