胆固醇氧化物作为1型和2型糖尿病氧化应激的生物标志物。

Cholesterol oxides as biomarkers of oxidative stress in type 1 and type 2 diabetes mellitus.

作者信息

Ferderbar S, Pereira E C, Apolinário E, Bertolami M C, Faludi A, Monte O, Calliari L E, Sales J E, Gagliardi A R, Xavier H T, Abdalla D S P

机构信息

Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.

出版信息

Diabetes Metab Res Rev. 2007 Jan;23(1):35-42. doi: 10.1002/dmrr.645.

DOI:10.1002/dmrr.645

PMID:16634125

Abstract

BACKGROUND

Oxidative stress plays an important role in the pathophysiology of diabetes mellitus. The aim of this study was to evaluate the formation of cholesterol oxides (ChOx) as biomarkers of oxidative stress in subjects with impaired glucose tolerance (IGT) and diabetes.

METHODS

Blood plasma levels of cholesterol oxidation products were determined in the following groups: type 1 diabetes mellitus (DM1), type 2 diabetes (DM2), impaired glucose tolerance (IGT), children without diabetes (C1) and adults without diabetes (C2). The serum levels of cholest-5-ene-3alpha,7alpha-diol (7alpha-hydroxycholesterol, 7alpha-OH), cholest-5-ene-3beta,7beta-diol (7beta-hydroxycholesterol, 7beta-OH), 3beta-hydroxycholest-5-7-one (7-ketocholesterol, 7-K), 5alpha-cholestane-3beta,5,6beta-triol (cholestanetriol), 5,6alpha-epoxy-5alpha-cholestan-3alpha-ol (cholesterol-5alpha,6alpha-epoxide,), 5,6beta-epoxy-5beta-cholestan-3beta-ol (cholesterol-5beta,6beta-epoxide) and cholest-5-eno-3beta,25-diol (25-hydroxycholesterol, 25-OH) (trivial name and abbreviations indicated in parentheses) were quantified by gas chromatography using flame ionization detection.

RESULTS

The levels of total ChOx were elevated in the DM1 and DM2 groups compared to age-matched subjects without diabetes (p < 0.05). The concentrations of 7beta-hydroxycholesterol, cholesterol-alpha-epoxide and cholesterol-beta-epoxide were higher in the blood plasma of subjects in the DM2 group than in the blood plasma of subjects in the C2 and IGT groups (p < 0.05). Treatment of type 2 diabetic patients with oral hypoglycemic drugs associated with insulin resulted in lower concentrations of nitrotyrosine in the blood plasma without significant changes in the concentrations of glucose and glycated hemoglobin. Moreover, combination with statins in both treatments decreased the concentrations of ChOx.

CONCLUSIONS

ChOx are suitable biomarkers of oxidative stress and may be useful in clinical studies to follow drug effects on lipid oxidative modifications in diabetic patients.

摘要

背景

氧化应激在糖尿病的病理生理学中起重要作用。本研究的目的是评估胆固醇氧化物（ChOx）的形成，作为葡萄糖耐量受损（IGT）和糖尿病患者氧化应激的生物标志物。

方法

测定以下几组人群血浆中胆固醇氧化产物的水平：1型糖尿病（DM1）、2型糖尿病（DM2）、葡萄糖耐量受损（IGT）、无糖尿病儿童（C1）和无糖尿病成人（C2）。采用火焰离子化检测气相色谱法定量测定血清中胆甾-5-烯-3α,7α-二醇（7α-羟基胆固醇，7α-OH）、胆甾-5-烯-3β,7β-二醇（7β-羟基胆固醇，7β-OH）、3β-羟基胆甾-5,7-二酮（7-酮胆固醇，7-K）、5α-胆甾烷-3β,5,6β-三醇（胆甾三醇）、5,6α-环氧-5α-胆甾烷-3α-醇（胆固醇-5α,6α-环氧化物）、5,6β-环氧-5β-胆甾烷-3β-醇（胆固醇-5β,6β-环氧化物）和胆甾-5-烯-3β,25-二醇（25-羟基胆固醇，25-OH）（括号内为俗名和缩写）的水平。

结果

与年龄匹配的无糖尿病受试者相比，DM1和DM2组的总ChOx水平升高（p < 0.05）。DM2组受试者血浆中7β-羟基胆固醇、胆固醇-α-环氧化物和胆固醇-β-环氧化物的浓度高于C2组和IGT组受试者血浆中的浓度（p < 0.05）。用口服降糖药联合胰岛素治疗2型糖尿病患者，可使血浆中硝基酪氨酸浓度降低，而血糖和糖化血红蛋白浓度无明显变化。此外，两种治疗方法联合使用他汀类药物均可降低ChOx浓度。