褪黑素通过H IF-1α/VEGF信号通路减轻急性肾损伤的研究

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摘要目的探讨脂多糖（LPS）诱导的急性肾损伤中低氧诱导因子1α（HIF-1α）和血管内皮生长因子（VEGF）的表达及褪黑素（Mel）对其表达的影响。方法选取3～5周龄的30只Sprague-Dawley（SD）大鼠作为研究对象，随机分为对照组（n=10）、LPS组（n=10，静脉注射500μg/kg LPS）、Mel+LPS组（n=10，注射LPS之前15min给予Mel）。48 h后采用TBA法检测肾组织的丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性，分别用RT-qPCR和免疫组化检测HIF-1α、VEGFmRNA和蛋白表达水平。结果LPS组肾小管上皮细胞肿胀、肾间质水肿，有炎细胞浸润；Mel+ LPS组的上述表现明显减轻。LPS组血清BUN和Scr含量［（35.56±1.83）mmol/L和（46.23±2.87）μmol/L］显著高于对照组［（12.69±0.97）mmol/L和（16.73±1.26）μmol/L］以及Mel+LPS组［（23.17±1.33）mmol/L和（35.67±2.25）μmol/L］（P＜0.05）。LPS组小鼠肾组织的MDA水平［（697.45±43.13）nmol/（mg·prot）］与对照组［（354.35±28.12）nmol/（mg·prot）］比较急剧增高（P＜0.05），Mel+LPS组的MDA［（455.37±30.79）nmol/（mg·prot）］与LPS组比较则明显降低（P＜0.05）。LPS组小鼠肾组织的SOD水平［（3.75±0.23）U/（mg·prot）］与对照组［（2.93±0.29）U/（mg·prot）］比较急剧降低（P＜0.05），Mel+LPS组的SOD水平［（3.20±0.27）U/（mg·prot）］与LPS组比较明显增高（P＜0.05）。LPS组小鼠肾组织的HIF-1α、VEGFmRNA和蛋白水平与对照组相比急剧增高（P＜0.05），Mel+LPS组与LPS组比较明显降低（P＜0.05）。结论Mel通过抑制MDA的产生和上调SOD的活性，调控HIF-1α和VEGF的表达，起到了保护LPS诱导的急性肾损伤（AKI）肾脏功能的作用。

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	冯杰
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	查艳

关键词 ：褪黑素, 肾损伤低氧诱导因子1&alpha, 血管内皮生长因子

Abstract：Objective To investigate the expression and influence ofmelatonin on hypoxia-inducible factor（HIF-1α）and vascular endothelial growth factor（VEGF）in acute kidney injury induced by lipopolysaccharide（LPS）. Methods 30 Sprague-Dawly（3-5 weeks）ratswere selected and randomly divided into the control group（n=10），the LPS group（n= 10，500μg/kg LPSwas injected intravenously）and the Mel+LPSgroup（n=10，melatonin was administrated orally，15min later，LPSwas given），followed by 48 hours，the ratswere killed.The thiobarbituric acid（TBA）testwas given to detect the level of MDA and the activity of superoxide dismutase （SOD）.The mRNAs and proteins of HIF-1αand VEGF were determined by RT-qPCR and immunohistochemistry.Results There was renal tubular epithelial cells swelling，renal interstitial edema and inflammation in the LPS group，those symptoms was attenuant in Mel+LSP group.The level of Scr and BUN in the LPS group［（35.56±1.83）mmol/L and　（46.23±2.87）μmol/L］was higher than that in the control group　［（12.69±0.97）mmol/L and （16.73±1.26）μmol/L］and the Mel+LPSgroup［（23.17±1.33）mmol/L and（35.67±2.25）μmol/L］（P＜0.05）.The level of MDA in the LPSgroup ［（697.45±43.13）nmol/（mg·prot）］was higher than that in the control group　［（354.35±28.12）nmol/（mg· prot）］and the level of MDA in the Mel+LPS group　［（455.37±30.79）nmol/（mg·prot）］was lower than that in the LPS group　（P＜0.05）.The level of SOD in the LPS group　［（3.75±0.23）U/（mg·prot）］was lower than that in the control group［（2.93±0.29）U/（mg·prot）］and Mel+LPSgroup［（3.20±0.27）U/（mg·prot）］（P＜0.05）.The level of HIF-1αand VEGFmRNA and protein in the LPS group was higher than that in the control group，and less than that in the Mel+LPS group.Con-clusion By inhibiting the production of MDA and up regulating the activity of SOD，Melcan regulate the expression of VEGF and HIF-1α，and plays a role in protecting LPS induced AKI renal function.

Key words： Melatonin；Renal injury hypoxia inducible factor-1&alpha ；Vascular endothelial growth factor

基金资助:贵州省科学技术基金项目（黔科合J字［2012］2230号）

作者简介: 冯杰（1970-），女，主任医师，研究方向：小儿肾脏病佟小雅（1987-），女，住院医师，研究方向：肾脏病、血管通路

引用本文:

冯杰;佟小雅;俞佳丽;潘祉谕;查艳. 褪黑素通过H IF-1α/VEGF信号通路减轻急性肾损伤的研究[J]. 中国当代医药, 2016, 23(29): 12-15.
FENG Jie;TONG Xiao-ya;YU Jia-li;PAN Zi-yu;ZHA Yan. Study on melatonin alleviated acute kidney injury through the HIF-1α/ VEGF pathway. 中国当代医药, 2016, 23(29): 12-15.

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［1］	Mei S，Livingston M，Hao J，et al.Autophagy is activated to protect against endotoxic acute kidney injury［J］.Sci Rep，2016，26（6）：22171.
［2］	Ogura Y，Jesmin S，Yamaguchi N，et al.Potential amelioration of upregulated renal HIF-1 alpha-endothelin-1 system by landiolol hydrochloride in a ratmodel of endotoxemia［J］. Life Sci，2014，118（2）：347-356.
［3］	Shiroma ME，Botelho NM，Damous LL，et al.Melatonin influence in ovary transplantation：systematic review［J］.JOvarian Res，2016，9（1）：33.
［4］	Mehta R，Drawz PE.Is nocturnal blood pressure reduction the secret to reducing the rate of progression of hypertensive chronic kidney disease？［J］.Curr Hypertens Rep，2011，13（5）：378-385.
［5］	Li S，Xu M，Niu Q，et al.Efficacy of procyanidins against in vivo cellularoxidative damage：a systematic review and Metaanalysis［J］.PLoSOne，2015，10（10）：e0139455.
［6］	Manquián-Cerda K，Escudey M，ZúnigaG，et al.Effect of cadmium on phenolic compounds，antioxidantenzymeactivity and oxidative stress in blueberry Vaccinium corymbosum L. plantlets grown in vitro［J］.Ecotoxicol Environ Saf，2016，133：316-326.
［7］	Xuan RR，Niu TT，Chen HM.Astaxanthin blocks preeclampsia progression by suppressing oxidative stress and inflammation［J］.Mol Med Rep，2016.［Epub ahead of print］
［8］	Ma J，Liu B.The effect ofmicrowave radiation on the levels ofMDA and the activity of SOD ofnasopharyngeal carcinoma cells［J］.Lin Chung Er Bi Yan Hou Tou JingWai Ke Za Zhi，2008，22（4）：160-162.
［9］	Flint A，Stintzi A，Saraiva LM.Oxidative and　nitrosative stress defences of Helicobacter and Campylobacter species thatcounteractmammalian immunity［J］.FEMSMicrobiolRev，2016.［Epub ahead of print］
［10］	Martini D，Del Bo′C，Tassotti M，et al.Coffee consumption and oxidative stress：a review of human intervention studies［J］.Molecules，2016，21（8）：pii：E979.
［11］	Lalkovic ováM，DanielisováV.Neuroprotection and antioxidants［J］.Neural Regen Res，2016，11（6）：865-874.
［12］	Sasabe E，Yang Z，Ohno S，et al.Reactive oxygen species produced by the knockdown ofmanganese-superoxide dismutase up-regulatehypoxia-inducible factor-1 alpha expression in oral squamous cell carcinoma cells［J］.Free Radic Biol Med，2010，48（10）：1321-1319.
［13］	Vriend J，Reiter RJ.Melatonin and the von Hippel-Lindau/ HIF-1 oxygen sensing mechanism：a review［J］.Biochim Biophys Acta，2016，1865（2）：176-183.
［14］	Ozdemir G，Ergün Y，Bakariu S，et al.Melatonin prevents retinal oxidative stress and vascular changes in diabetic rats［J］.Eye（Lond），2014，28（8）：1020-1027.
［15］	Sanchez-Sanchez AM，Antolin I，Puente-Moncada N，et al. Melatonin cytotoxicity is associated to warburg effect inhibition in ewing sarcoma cells［J］.PLoS One，2015，10（8）：e0135420.