Vitamin D3 pretreatment alleviates renal oxidative stress in lipopolysaccharide-induced acute kidney injury
Vitamin D3 pretreatment alleviates renal oxidative stress in lipopolysaccharide-induced acute kidney injury
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维生素 D3 预处理可减轻脂多糖诱导的急性肾损伤中的肾脏氧化应激
DOI：
10.1016/j.jsbmb.2015.05.009
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发表时间：
2015-08
影响因子：
4.1
通讯作者：
Yu De-Xin
中科院分区：
文献类型：
--
作者：
Xu Shen;Chen Yuan-Hua;Tan Zhu-Xia;Xie Dong-Dong;Zhang Cheng;Xia Mi-Zhen;Wang Hua;Zhao Hui;Xu De-Xiang;Yu De-Xin
越来越多的证据表明活性氧在脓毒症引起的急性肾损伤中起重要作用。本研究探讨了VitD 3预处理对脓毒症所致急性肾损伤肾脏氧化应激的影响。腹腔注射脂多糖（LPS，2.0 mg/kg）建立脓毒症急性肾损伤动物模型。VitD 3 + LPS组于注射LPS前1、24、48 h分别灌胃VitD 3（25 μg/kg）。正如预期的那样，每日3次口服推荐剂量的VitD 3可显著升高血清25（OH）D浓度，并有效激活肾脏VDR信号。有趣的是，LPS诱导的肾脏GSH耗竭和脂质过氧化反应在VitD 3预处理的小鼠显着减轻。VitD 3预处理可明显抑制LPS诱导的血清和肾脏一氧化氮（NO）的产生。此外，LPS诱导的肾脏蛋白质硝化，由3-硝基酪氨酸残基测定，明显减弱VitD 3预处理。进一步的分析表明，LPS诱导的上调肾脏诱导型一氧化氮合酶（inos）在VitD 3预处理的小鼠被抑制。LPS诱导的NADPH氧化酶亚基renalp 47 phox和gp 91 phox的上调可通过VitD 3预处理而恢复正常。此外，LPS诱导的肾脏超氧化物歧化酶（sod）1和sod 2，两种抗氧化酶基因的下调，在VitD 3预处理的小鼠中被逆转。最后，LPS诱导的肾小管上皮细胞凋亡，通过TUNEL法测定，减轻维生素D3预处理。综上所述，这些结果表明，VitD 3预处理减轻LPS诱导的肾脏氧化应激，通过调节氧化和抗氧化酶基因。
Increasing evidence demonstrates that reactive oxygen species plays important roles in sepsis-induced acute kidney injury. This study investigated the effects of VitD3 pretreatment on renal oxidative stress in sepsis-induced acute kidney injury. Mice were intraperitoneally injected with lipopolysaccharide (LPS, 2.0 mg/kg) to establish an animal model of sepsis-induced acute kidney injury. In VitD3 + LPS group, mice were orally pretreated with three doses of VitD3 (25 μg/kg) at 1, 24 and 48 h before LPS injection. As expected, oral pretreatment with three daily recommended doses of VitD3 markedly elevated serum 25(OH)D concentration and efficiently activated renal VDR signaling. Interestingly, LPS-induced renal GSH depletion and lipid peroxidation were markedly alleviated in VitD3-pretreated mice. LPS-induced serum and renal nitric oxide (NO) production was obviously suppressed by VitD3 pretreatment. In addition, LPS-induced renal protein nitration, as determined by 3-nitrotyrosine residue, was obviously attenuated by VitD3 pretreatment. Further analysis showed that LPS-induced up-regulation of renal inducible nitric oxide synthase (inos) was repressed in VitD3-pretreated mice. LPS-induced up-regulation of renalp47phoxandgp91phox, two NADPH oxidase subunits, were normalized by VitD3 pretreatment. In addition, LPS-induced down-regulation of renalsuperoxide dismutase (sod) 1andsod2,two antioxidant enzyme genes, was reversed in VitD3-pretreated mice. Finally, LPS-induced tubular epithelial cell apoptosis, as determined by TUNEL, was alleviated by VitD3 pretreatment. Taken together, these results suggest that VitD3 pretreatment alleviates LPS-induced renal oxidative stress through regulating oxidant and antioxidant enzyme genes.
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DOI：
10.1016/j.jsbmb.2013.09.014
发表时间：
2014-10
影响因子：
4.1
作者：
Li, Yan Chun;Chen, Yunzi;Liu, Weicheng;Thadhani, Ravi
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影响因子：
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10.1152/ajplung.00097.2011
发表时间：
2012-04-01
影响因子：
4.9
作者：
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影响因子：
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