白藜芦醇对高原脑水肿小鼠血管内皮生长因子表达的影响
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摘要
【目的】研究白藜芦醇对高原脑水肿小鼠脑组织的保护作用及血管内皮生长因子(vascular endothelial growth factor,VEGF)基因及蛋白表达的影响。【方法】成年雄性昆明种小鼠随机分为5组:常氧对照组、急性低氧组、白藜芦醇大、中、小剂量组;不同浓度白藜芦醇预处理小鼠1周,将其放入低压氧舱,模拟海拔8 000 m高度,缺氧24 h。HE染色观察小鼠脑组织形态学改变,real-time PCR检测VEGF mRNA表达变化,免疫组化和Western blotting方法检测VEGF蛋白表达变化。【结果】与急性低氧组比较,白藜芦醇预处理组小鼠脑组织形态结构接近常氧对照组,VEGF mRNA及蛋白表达均明显下调(P<0.05)。【结论】白藜芦醇能够减轻急性低压低氧导致的脑水肿,保护脑组织,此作用与其下调VEGF的表达,保护血脑屏障通透性有关。
【Objective】To study the protective effect of resveratrol on brain tissues and its regulation on the expression of vascular endothelial growth factor(VEGF) in mice with high-altitude cerebral edema.【Methods】The male Kunming mice were randomly divided into 5 groups: control group, acute hypoxia group, intervention groups with resveratrol in high, medium and low dose. The mice were pretreated with different concentrations of resveratrol for 1 w and placed in a hypobaric chamber which mimicked the height of 8000 m above sea level for 24 h. The microstructure changes in the cerebral tissues of mice were observed via HE staining, real-time PCR, immunohistochemistry and Western blotting were used for detecting the m RNA and protein expressions of VEGF.【Results】Compared with acute hypoxia group, the microstructures were improved in the intervention groups with resveratrol. The m RNA and protein levels of VEGF were down-regulated obviously(P< 0.05).【Conclusion】Resveratrol can attenuate cerebral edema caused by hypobaric hypoxia and protect brain from injury. This action may be related with its effect of down-regulating the expression of VEGF.
【Objective】To study the protective effect of resveratrol on brain tissues and its regulation on the expression of vascular endothelial growth factor(VEGF) in mice with high-altitude cerebral edema.【Methods】The male Kunming mice were randomly divided into 5 groups: control group, acute hypoxia group, intervention groups with resveratrol in high, medium and low dose. The mice were pretreated with different concentrations of resveratrol for 1 w and placed in a hypobaric chamber which mimicked the height of 8000 m above sea level for 24 h. The microstructure changes in the cerebral tissues of mice were observed via HE staining, real-time PCR, immunohistochemistry and Western blotting were used for detecting the m RNA and protein expressions of VEGF.【Results】Compared with acute hypoxia group, the microstructures were improved in the intervention groups with resveratrol. The m RNA and protein levels of VEGF were down-regulated obviously(P< 0.05).【Conclusion】Resveratrol can attenuate cerebral edema caused by hypobaric hypoxia and protect brain from injury. This action may be related with its effect of down-regulating the expression of VEGF.
引文
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[10]Wei H,Wang S,Zhen L,et al.Resveratrol attenuates the blood-brain barrier dysfunction by regulation of the MMP-9/TIMP-1 balance after cerebral ischemia reperfusion in rats[J].J Mol Neurosci,2015,55(4):872-879.
[11]Li WL,Zhang L,Zhang YL.Effects of resveratrol on proliferation of retinal vascular endothelial cells and expression of VEGF[J].2008,8(6):1087-1090.
[12]Tino AB,Chitcholtan K,Sykes PH,et al.Resveratrol and acetyl-resveratrol modulate activity of VEGF and IL-8 in ovarian cancer cell aggregates via attenuation of the NF-κBprotein[J].J Ovarian Res,2016,9(1):84-95.
[2]Sarkar A,Angeline MS,Anand K,et al.Naringenin and quercetinreverse the effect of hypobaric hypoxia and elicit neuroprotectiveresponse in the murine model[J].Brain Res,2012,1481(30):59-70.
[3]Roach RC,Hackett PH.Frontiers of hypoxia research:acute mountain sickness[J].J Exp Biol,2001,204(Pt18):3161-3170.
[4]Hackett PH,Roach RC.High altitude cerebral edema[J].High Alt Med Biol,2004,5(2):136-146.
[5]Cai GX,Liu BY.Buyang Huanwu decoction increases vascular endothelial growth factor expression and promotes angiogenesis in a rat model of local cerebral ischemia[J].Neural Regen Res,2010,5(22):1733-1738.
[6]Zhou QQ,Liu CE,Wang J,et al.Correlation of vascular endothelia growth factor to permeability of blood-brain barrier and brain edema during high-altitude exposure[J].Neural Regen Res,2009,4(10):775-779.
[7]Fischer S,Wohben M,Marti HH,et al.Hypoxia induced hyperpermeability in brain microvessel endothelial cells involves VEGF mediated changes in the expression of zonulaoccludens[J].Micmvasc Res,2002,63(1):70-80.
[8]夏丽萍,谢金洲.白藜芦醇的药理作用进展[J].中国误诊学杂志,2006,2(6):220-222.
[9]Renaud J,Martinoli MG.Resveratrol as a protective molecule for neuroinflammation:a review of mechanisms[J].Curr Pharm Biotechnol,2014,15(4):318-329.
[10]Wei H,Wang S,Zhen L,et al.Resveratrol attenuates the blood-brain barrier dysfunction by regulation of the MMP-9/TIMP-1 balance after cerebral ischemia reperfusion in rats[J].J Mol Neurosci,2015,55(4):872-879.
[11]Li WL,Zhang L,Zhang YL.Effects of resveratrol on proliferation of retinal vascular endothelial cells and expression of VEGF[J].2008,8(6):1087-1090.
[12]Tino AB,Chitcholtan K,Sykes PH,et al.Resveratrol and acetyl-resveratrol modulate activity of VEGF and IL-8 in ovarian cancer cell aggregates via attenuation of the NF-κBprotein[J].J Ovarian Res,2016,9(1):84-95.