血浆CoQ_（10）的含量测定及其与甲状腺疾病相关性的初步研究
摘要
辅酶Q_(10)(CoQ_(10))是一种重要的维他命样脂溶性物质，主要位于细胞线粒体。作为至少三种线粒体酶(复合物Ⅰ、Ⅱ和Ⅲ)的辅酶，它参与线粒体呼吸链上氧化磷酸化反应中的电子传递，因而是细胞能量三磷酸腺甙(ATP)生成过程中不可缺少的组成成分。CoQ_(10)同时也是一种重要的抗氧化物质，有保持细胞膜稳定的功能，即能防止膜脂质过氧化和保持膜流动性，因此其在脂蛋白以及血浆中的含量被认为体内氧化应激的标志。CoQ_(10)的含量水平和很多疾病的发生、发展都直接或间接相关，检测CoQ_(10)的含量具有重要的医学意义。过去对CoQ_(10)的研究主要集中在心脏疾病治疗方面，对内分泌疾病如甲状腺疾病的研究较少。
本文优化了测定CoQ_(10)的SPE-HPLC方法，通过对固相萃取(SPE)柱容量的选择，大大提高了测定的灵敏度。选用合适的提取溶剂，简化了血浆样品的预处理过程，并建立了测定血浆CoQ_(10)的HPLC方法。针对测定过程中存在繁琐、耗时的手动样品预处理问题，构建了一个样品预处理和分离一体化的柱切换液相色谱在线系统，并首次在该系统上建立了分析血浆CoQ_(10)的方法，实现了血样的自动预处理、自动进样以及CoQ_(10)的自动分离和定量功能。大大减少了所需的样品量和分析时间，提高了分析结果的精密度。该方法灵敏度高，检测限达0.1mg/L。应用该方法测定了甲亢、甲减以及正常人血浆CoQ_(10)的含量水平，比较了三者含量水平的显著性差异，同时探索了CoQ_(10)的含量与甲状腺激素之间的相关性关系。结果表明，甲亢病人血浆CoQ_(10)浓度最低，甲减病人较高，与正常对照组相比较，均存在显著性差异，CoQ_(10)的含量与甲状腺激素之间存在显著的线性负相关关系。
此外，本文首次建立了化妆品中CoQ_(10)含量测定的RP-HPLC方法，该方法利用固相萃取(SPE)技术浓缩和净化样品，有效地保护了柱寿命，同时该方法重现性好，灵敏度高(检测限达0.04mg/L)。用该方法对同一品牌的系列化妆品中CoQ_(10)进行了测定，两者的含量基本一致。
Coenzyme Q10 (CoQ10) is essentially a vitamin-like and lipophilic compound which mainly locates in the mitochondria. As the coenzyme for at least three mitochondrial enzymes (complexes I, II and III) as well as enzymes in other parts of the cell, CoQ10 functions as a cofactor in the electron transport of oxidative phosphorylation, so it is essential for production of cellular energy in the form of phosphate adenosine triphosphate (ATP). Moreover, CoQ10 has been studied as an antioxident agent for stabilizing membrane, that is, avoiding lipid peroxidation and regulating lipid fluidity. Therefore, it's concentration in lipoproteins and plasma may be a useful marker of oxidative stress. The content of CoQ10 is thought relevant to the causes and development of some diseases directly or indirectly, so the measurement is of considerable importance in clinical chemistry laboratories. In past, more clinical work with CoQ10 has focused on heart disease and little on endocrinopathy such as thyroid disease.
The method based on SPE-HPLC for determining CoQ10 in plasma was optimizd with higher sensitivity by selecting the column capacity of SPE. Another HPLC method for assaying CoQ10 in plasma was developed with the simplified extraction of CoQ10. Current HPLC analysis of CoQ10 involves laborious and time-consuming manual sample processing steps due to the complexity of the sample matrix. A liquid chromatography on-line system based on column-switching that can be used for integrating sample pretreatment and analysis was set up, and the new method for determining CoQ10 in human plasma was established on this system. Small sample volume shorten analysis time and improved analytical precision are obtained for the on-line procedure. The method shows high sensitivity, the detection limit of which is 0.1mg/L. Using this method, the CoQ10 concentration of healthy subjects, hyperthyroid and hypothyroid patients were evaluated. The results shows the levels of CoQ10 have a significant difference among these subjects, and there lies a significant inverse correlation between the level of the thyroid hormones and that of the CoQ10.
Moreover, the new RP-HPLC method based on SPE for assaying CoQ10 in cosmetic is developed. The method shows good reproducibility, high sensitivity (the detection limit is 0.04mg/L). Series cosmetic of the same product was investigated, and the same content of CoQio was found.
本文优化了测定CoQ_(10)的SPE-HPLC方法，通过对固相萃取(SPE)柱容量的选择，大大提高了测定的灵敏度。选用合适的提取溶剂，简化了血浆样品的预处理过程，并建立了测定血浆CoQ_(10)的HPLC方法。针对测定过程中存在繁琐、耗时的手动样品预处理问题，构建了一个样品预处理和分离一体化的柱切换液相色谱在线系统，并首次在该系统上建立了分析血浆CoQ_(10)的方法，实现了血样的自动预处理、自动进样以及CoQ_(10)的自动分离和定量功能。大大减少了所需的样品量和分析时间，提高了分析结果的精密度。该方法灵敏度高，检测限达0.1mg/L。应用该方法测定了甲亢、甲减以及正常人血浆CoQ_(10)的含量水平，比较了三者含量水平的显著性差异，同时探索了CoQ_(10)的含量与甲状腺激素之间的相关性关系。结果表明，甲亢病人血浆CoQ_(10)浓度最低，甲减病人较高，与正常对照组相比较，均存在显著性差异，CoQ_(10)的含量与甲状腺激素之间存在显著的线性负相关关系。
此外，本文首次建立了化妆品中CoQ_(10)含量测定的RP-HPLC方法，该方法利用固相萃取(SPE)技术浓缩和净化样品，有效地保护了柱寿命，同时该方法重现性好，灵敏度高(检测限达0.04mg/L)。用该方法对同一品牌的系列化妆品中CoQ_(10)进行了测定，两者的含量基本一致。
Coenzyme Q10 (CoQ10) is essentially a vitamin-like and lipophilic compound which mainly locates in the mitochondria. As the coenzyme for at least three mitochondrial enzymes (complexes I, II and III) as well as enzymes in other parts of the cell, CoQ10 functions as a cofactor in the electron transport of oxidative phosphorylation, so it is essential for production of cellular energy in the form of phosphate adenosine triphosphate (ATP). Moreover, CoQ10 has been studied as an antioxident agent for stabilizing membrane, that is, avoiding lipid peroxidation and regulating lipid fluidity. Therefore, it's concentration in lipoproteins and plasma may be a useful marker of oxidative stress. The content of CoQ10 is thought relevant to the causes and development of some diseases directly or indirectly, so the measurement is of considerable importance in clinical chemistry laboratories. In past, more clinical work with CoQ10 has focused on heart disease and little on endocrinopathy such as thyroid disease.
The method based on SPE-HPLC for determining CoQ10 in plasma was optimizd with higher sensitivity by selecting the column capacity of SPE. Another HPLC method for assaying CoQ10 in plasma was developed with the simplified extraction of CoQ10. Current HPLC analysis of CoQ10 involves laborious and time-consuming manual sample processing steps due to the complexity of the sample matrix. A liquid chromatography on-line system based on column-switching that can be used for integrating sample pretreatment and analysis was set up, and the new method for determining CoQ10 in human plasma was established on this system. Small sample volume shorten analysis time and improved analytical precision are obtained for the on-line procedure. The method shows high sensitivity, the detection limit of which is 0.1mg/L. Using this method, the CoQ10 concentration of healthy subjects, hyperthyroid and hypothyroid patients were evaluated. The results shows the levels of CoQ10 have a significant difference among these subjects, and there lies a significant inverse correlation between the level of the thyroid hormones and that of the CoQ10.
Moreover, the new RP-HPLC method based on SPE for assaying CoQ10 in cosmetic is developed. The method shows good reproducibility, high sensitivity (the detection limit is 0.04mg/L). Series cosmetic of the same product was investigated, and the same content of CoQio was found.
引文
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