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Effect of AVE 0991 angiotensin-( 1-7) receptor agonist treatment on elemental and biomolecular content and distribution in atherosclerotic plaques of apoE-knockout mice

机译:AVE 0991血管紧张素-(1-7)受体激动剂对apoE基因敲除小鼠动脉粥样硬化斑块中元素和生物分子含量及分布的影响

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Gene-targeted apolipoprotein E-knockout (apoE-KO) mice display early and highly progressive vascular lesions containing lipid deposits and they became a reliable animal model to study atherosclerosis. The aim of the present study was to investigate the effect of AVE 0991 angiotensin-(1-7) receptor agonist on the distribution of selected pro- and anti- inflammatory elements as well as biomolecules in atherosclerotic plaques of apoE-knockout mice. Synchrotron radiation-based X-ray fluorescence (micro-XRF) and Fourier Transform Infrared (micro-FTIR) microspectroscopies were applied. Two-month-old apoE-KO mice were fed for following four months diet supplemented with AVE 0991 (0.58 μmol/kg b.w. per day). Histological sections of ascending aortas were analyzed spectroscopically. The distribution of P, Ca, Fe and Zn were found to correspond with histological structure of the lesion. Significantly lower contents of P, Ca, Zn and significantly higher content of Fe were observed in animals treated with AVE 0991. Biomolecular analysis showed lower lipids saturation level and lower lipid to protein ratio in AVE 0991 treated group. Protein secondary structure was studied according to the composition of amide I band (1660 cm~(-1)) and it demonstrated higher proportion of p-sheet structure as compared to α-helix in both studied groups.
机译:以基因为靶点的载脂蛋白E基因敲除(apoE-KO)小鼠显示出早期和高度进展的包含脂质沉积物的血管病变,它们成为研究动脉粥样硬化的可靠动物模型。本研究的目的是研究AVE 0991血管紧张素-(1-7)受体激动剂对apoE基因敲除小鼠的动脉粥样硬化斑块中所选促炎和抗炎成分以及生物分子分布的影响。应用基于同步辐射的X射线荧光(micro-XRF)和傅立叶变换红外(micro-FTIR)显微光谱仪。给两个月大的apoE-KO小鼠喂食以下四个月的日粮,补充AVE 0991(每天0.58μmol/ kg b.w.)。光谱分析升主动脉的组织学切片。发现P,Ca,Fe和Zn的分布与病变的组织学结构相对应。在用AVE 0991处理的动物中,观察到P,Ca,Zn的含量显着降低,而Fe则显着升高。生物分子分析显示,在AVE 0991治疗组中,脂质饱和度较低,脂蛋白比率较低。根据酰胺I带(1660 cm〜(-1))的组成对蛋白质二级结构进行了研究,在两个研究组中,其蛋白质p-sheet结构的比例均高于α-螺旋。

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