Genistein Ameliorates Ischemia/Reperfusion-Induced Renal Injury in a SIRT1-Dependent Manner.
Genistein Ameliorates Ischemia/Reperfusion-Induced Renal Injury in a SIRT1-Dependent Manner.
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DOI：
10.3390/nu9040403
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发表时间：
2017-04-20
期刊：
影响因子：
5.9
通讯作者：
Huang WF
中科院分区：
文献类型：
--
作者：
Li WF;Yang K;Zhu P;Zhao HQ;Song YH;Liu KC;Huang WF
肾缺血/再灌注（I/R）损伤一直是临床实践中的复杂情况。染料木黄酮是豆制品中的主要生物碱，具有广泛的生物化学和药理活性。然而，染料木黄酮对肾I/R损伤的保护作用还没有得到很好的研究。在本研究中，我们探讨染料木黄酮是否通过SIRT 1（Sirtuin 1）在I/R诱导的小鼠模型中发挥其肾脏保护作用。我们发现染料木黄酮的治疗显着减少肾I/R诱导的细胞死亡，同时刺激肾细胞增殖。同时，SIRT 1表达上调后，金雀异黄素在肾区的管理。此外，药物抑制或shRNA介导的SIRT 1耗竭显着逆转了金雀异黄素对I/R损伤后肾功能障碍，细胞损伤，细胞凋亡和增殖的保护作用，这表明SIRT 1表达和活性增加在此过程中不可或缺的作用。同时，与金雀异黄素治疗组相比，SIRT 1耗竭后，肾I/R过程中p53、p21蛋白表达的降低和PCNA（增殖细胞核抗原）蛋白表达的升高被阻断。因此，我们的研究结果提供了进一步的实验基础，金雀异黄素的潜在用途，用于治疗肾脏疾病的SIRT 1活性的缺陷。
Renal ischemia/reperfusion (I/R) injury continues to be a complicated situation in clinical practice. Genistein, the main isoflavone found in soy products, is known to possess a wide spectrum of biochemical and pharmacological activities. However, the protective effect of genistein on renal I/R injury has not been well investigated. In the current study, we explore whether genistein exhibits its renal-protective effects through SIRT1 (Sirtuin 1) in I/R-induced mice model. We found the treatment of genistein significantly reduced renal I/R-induced cell death, simultaneously stimulating renal cell proliferation. Meanwhile, SIRT1 expression was up-regulated following the administration of genistein in renal region. Furthermore, pharmacological inhibition or shRNA-mediated depletion of SIRT1 significantly reversed the protective effect of genistein on renal dysfunction, cellular damage, apoptosis, and proliferation following I/R injury, suggesting an indispensible role of the increased SIRT1 expression and activity in this process. Meanwhile, the reduced p53 and p21 expression and increased PCNA (Proliferating Cell Nuclear Antigen) expression were blocked after the depletion of SIRT1 compared with the genistein treatment group in the renal I/R process. Hence, our results provided further experimental basis for the potential use of genistein for the treatment of kidney disease with deficiency of SIRT1 activity.