Involvement of peroxisome proliferator-eactivated receptor gamma in vitamin D-emediated protection against acute kidney injury in rats
Involvement of peroxisome proliferator-eactivated receptor gamma in vitamin D-emediated protection against acute kidney injury in rats
复制标题
DOI：
10.1016/j.jss.2013.07.017
复制
发表时间：
2013-12-01
影响因子：
2.2
通讯作者：
Singh, Amrit Pal
中科院分区：
文献类型：
--
作者：
Kapil, Akanksha;Singh, Jaswinder Pal;Singh, Amrit Pal
背景：维生素 D 在多项研究中被报道为肾脏保护剂。最近，一些体外研究强调了维生素 D 和过氧化物酶体增殖物再激活受体 γ (PPAR-g) 之间的相互作用。本研究探讨了 PPAR-g 的激活作为维生素介导的大鼠缺血再灌注诱导的急性肾损伤 (AKI) 保护的新机制。 材料和方法：通过夹住肾蒂 40 分钟，然后再灌注 24 小时来诱导 AKI。通过测量肌酐清除率、血清尿素、尿酸水平和乳酸脱氢酶活性来评估 AKI。此外，还测量了大鼠的血清钾、钙水平、钠排泄分数和微量蛋白尿。通过定量硫代巴比妥酸反应物质、超氧阴离子生成、还原型谷胱甘肽水平以及过氧化氢酶和髓过氧化物酶活性来评估肾组织中的氧化应激。苏木精-伊红染色观察肾组织的组织病理学变化。在对大鼠进行肾缺血再灌注损伤（IRI）前给予维生素D（0.25、0.5和1 mg/kg）7 d。结果：大鼠肾脏IRI引起血清、尿液和肾组织氧化应激参数的显着变化。此外，苏木精-伊红染色显示 IRI 对肾组织造成明显损伤。给予 0.5 mg/kg 剂量的维生素 D 可最大程度地预防肾 IRI。先前用 PPAR-g 拮抗剂双酚 A 二缩水甘油醚治疗显着减弱了维生素 D 的保护作用，从而证实了 PPAR-g 参与了维生素介导的肾脏保护作用。结论：得出的结论是，PPAR-g 的激活显着有助于维生素介导的对缺血再灌注诱导的 AKI 的保护。 (C) 2013 Elsevier Inc. 保留所有权利。
Background: Vitamin D has been reported as renoprotective agents in various studies. Recently, a few in vitro studies highlighted cross talk between vitamin D and peroxisome proliferatoreactivated receptor gamma (PPAR-g). The present study investigated the activation of PPAR-g as novel mechanism in vitamin Demediated protection against ischemia reperfusioneinduced acute kidney injury (AKI) in rats.Materials and methods: The AKI was induced by clamping renal pedicles for 40 min followed by reperfusion for 24 h. The AKI was assessed by measuring creatinine clearance, serum urea, uric acid level, and lactate dehydrogenase activity. Moreover, serum potassium, calcium level, fractional excretion of sodium, and microproteinuria were measured in rats. The oxidative stress in renal tissues was assessed by quantification of thiobarbituric acide reactive substances, superoxide anion generation, reduced glutathione level, and catalase and myeloperoxidase activities. The hematoxylin-eosin staining was carried out to observe histopathologic changes in renal tissues. Vitamin D (0.25, 0.5, and 1 mg/ kg) was administered for 7 d before subjecting rats to renal ischemia reperfusion injury (IRI).Results: The renal IRI in rats induced significant changes in serum, urinary, and oxidative stress parameters in renal tissues. Moreover, hematoxylin-eosin staining revealed marked damage produced by IRI in renal tissues. The administration of vitamin D at 0.5 mg/kg dose afforded maximum protection against renal IRI. The prior treatment with PPAR-g antagonist bisphenol A diglycidyl ether significantly attenuated protective effect of vitamin D, thus confirming involvement of PPAR-g in vitamin Demediated renoprotection.Conclusions: It is concluded that activation of PPAR-g significantly contributes toward vitamin Demediated protection against ischemia reperfusioneinduced AKI. (C) 2013 Elsevier Inc. All rights reserved.