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首页> 外文期刊>Journal of Applied Life Sciences International >Activation of Nrf2 Restores Klotho Expression and Attenuates Oxidative Stress and Inflammation in CKD
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Activation of Nrf2 Restores Klotho Expression and Attenuates Oxidative Stress and Inflammation in CKD

机译：Nrf2的激活可恢复Klotho的表达并减轻CKD中的氧化应激和炎症。

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Background: Chronic kidney disease (CKD) causes klotho deficiency, oxidative stress and inflammation which are common features and major mediators of progression of renal disease. Oxidative stress in CKD is, partly, due to impaired activation of Nrf2, the master regulator of genes encoding antioxidant and cytoprotective molecules. Oxidative stress inhibits klotho expression in the kidney. Given the role of Nrf2 dysfunction in the pathogenesis of oxidative stress in CKD, we hypothesized that treatment with Nrf2 activator, dh404, may restore renal klotho expression and attenuate oxidative stress and inflammation in CKD. Methods: Male SD rats were subjected to 5/6 nephrectomy (CKD) or sham operation. The CKD rats were randomized to receive dh404 (2mg/kg/day) or vehicle for 12 weeks. At the conclusion of the observation period tail arterial pressure was measured and 24-hr urine was collected. Animals were then euthanized and blood and kidneys were harvested. Results: Compared to the control group, untreated CKD rats exhibited marked reduction of klotho abundance in the remnant kidney. This was associated with interstitial inflammation, local and systemic oxidative stress, NFkB activation, impaired Nrf2 activity and reduced expression of the key Nrf2 target gene products. Administration of dh404 reversed klotho deficiency, restored Nrf2 activity and expression of its key target gene products and attenuated oxidative stress and inflammation and NFkB activity in the renal tissue. Conclusion: Restoration of Nrf2 activity reversed klotho deficiency and attenuated oxidative stress and inflammation in remnant kidneys of CKD rats.
机译：背景：慢性肾脏病（CKD）导致klotho缺乏症，氧化应激和炎症，这是肾脏疾病进展的常见特征和主要介质。 CKD中的氧化应激部分是由于Nrf2的激活受损，Nrf2是编码抗氧化剂和细胞保护分子的基因的主要调控因子。氧化应激会抑制肾脏中的klotho表达。鉴于Nrf2功能障碍在CKD氧化应激的发病机理中的作用，我们假设用Nrf2激活剂dh404进行治疗可以恢复肾脏的klotho表达并减轻CKD的氧化应激和炎症。方法：雄性SD大鼠接受5/6肾切除术（CKD）或假手术。 CKD大鼠随机接受dh404（2mg / kg /天）或赋形剂治疗12周。在观察期结束时，测量尾动脉压并收集24小时尿液。然后对动物实施安乐死，并收集血液和肾脏。结果：与对照组相比，未治疗的CKD大鼠的残余肾脏中klotho丰度明显降低。这与间质炎症，局部和全身氧化应激，NF k B活化，Nrf2活性受损以及关键Nrf2靶基因产物表达降低有关。施用dh404可以逆转klotho缺乏症，恢复Nrf2活性及其关键靶基因产物的表达，并减轻肾脏组织中的氧化应激和炎症以及NF k B活性。结论：恢复Nrf2活性可逆转CKD大鼠残余肾脏的klotho缺乏症，并减轻氧化应激和炎症。

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