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家族性高胆固醇血症氧化应激状态评估

Evaluation of Oxidative Stress Status in Familial Hypercholesterolemia.

作者信息

Ganjali Shiva, Keshavarz Reihaneh, Hosseini Susan, Mansouri Atena, Mannarino Massimo R, Pirro Matteo, Jamialahmadi Tannaz, Sahebkar Amirhossein

机构信息

Department of Medical Biotechnology and Nanotechnology, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran.

Department of Genetics, Faculty of Biological Sciences, Tehran North Branch, Islamic Azad University, Tehran 1651153311, Iran.

出版信息

J Clin Med. 2021 Dec 14;10(24):5867. doi: 10.3390/jcm10245867.

Abstract

BACKGROUND

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characterizied by elevated levels of circulating low-density lipoprotein cholesterol (LDL-C) which is an important source of substrates to be oxidized by different oxidative agents. Subsequently, the oxidized LDLs (oxLDLs) induce further oxidative reactions in FH patients, which contributes to the development of atherosclerosis and advanced cardiovascular events in these patients. This study aimed to investigate the association of oxidant/antioxidant markers with FH.

METHODS

This case-control study comprised 18 HoFH, 18 HeFH, and 20 healthy subjects. Oxidant/antioxidant markers including MDA, MPO, thiol, nitric oxide (NO), myeloperoxidase (MPO), glutathione peroxidase (GPx), SOD, and CAT were assessed by colorimetric methods. Prooxidant-antioxidant balance was also measured by pro-oxidant antioxidant balance (PAB) assay.

RESULTS

The levels of MDA ( < 0.001), MPO activity ( < 0.001), thiol ( < 0.001), NO ( < 0.01), and PAB ( < 0.001) were notably higher in HoFH group in comparison with healthy subjects. HeFH group also showed significantly higher levels of thiol ( < 0.001) and PAB ( < 0.001) when compared to healthy subjects. Elevated levels of MDA ( < 0.001) and PAB ( < 0.001) were also observed in HoFH relative to HeFH. No significant differences were found between the studied groups in the case of antioxidant enzyme activities. The results of binary logistic regression showed that PAB (OR: 0.979; = 0.033), and MDA (OR: 0.996; = 0.018) levels were inversely associated with HoFH, although, after adjustment for age and LDL-C levels, these associations were diminished.

CONCLUSION

Several oxidant/antioxidant differences were found between FH patients and healthy individuals as well as between HoFH and HeFH patients. These differences might be strongly dependent on plasma LDL-C levels.

摘要

背景

家族性高胆固醇血症(FH)是一种常染色体显性遗传疾病,其特征是循环中的低密度脂蛋白胆固醇(LDL-C)水平升高,LDL-C是不同氧化剂氧化的重要底物来源。随后,氧化型低密度脂蛋白(oxLDLs)在FH患者中诱导进一步的氧化反应,这促成了这些患者动脉粥样硬化和严重心血管事件的发生。本研究旨在调查氧化/抗氧化标志物与FH的关联。

方法

本病例对照研究包括18例纯合子家族性高胆固醇血症(HoFH)患者、18例杂合子家族性高胆固醇血症(HeFH)患者和20名健康受试者。通过比色法评估氧化/抗氧化标志物,包括丙二醛(MDA)、髓过氧化物酶(MPO)、硫醇、一氧化氮(NO)、髓过氧化物酶(MPO)、谷胱甘肽过氧化物酶(GPx)、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)。还通过促氧化剂-抗氧化剂平衡(PAB)测定法测量促氧化剂-抗氧化剂平衡。

结果

与健康受试者相比,HoFH组的MDA水平(<0.001)、MPO活性(<0.001)、硫醇水平(<0.001)、NO水平(<0.01)和PAB水平(<0.001)显著更高。与健康受试者相比,HeFH组的硫醇水平(<0.001)和PAB水平(<0.001)也显著更高。与HeFH相比,HoFH中MDA水平(<0.001)和PAB水平(<0.001)也有所升高。在抗氧化酶活性方面,研究组之间未发现显著差异。二元逻辑回归结果显示,PAB水平(比值比:0.979;P = 0.033)和MDA水平(比值比:0.996;P = 0.018)与HoFH呈负相关,不过,在调整年龄和LDL-C水平后,这些关联减弱。

结论

在FH患者与健康个体之间以及HoFH和HeFH患者之间发现了几种氧化/抗氧化差异。这些差异可能强烈依赖于血浆LDL-C水平。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bebf/8707741/a499d37aacd0/jcm-10-05867-g001.jpg

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