3β，5α，6β-三羟胆固醇对小鼠肝线粒体的氧化损伤及相关机理研究
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摘要
动脉粥样硬化(AS)是严重威胁人类的疾病之一,氧化型胆固醇被认为是AS的主要致病因素。揭示氧化型胆固醇的细胞毒性作用及其机制、研究AS发生和发展的防治,仍然是当前人口与健康研究领域的前沿课题之一。
本论文以分离的小鼠肝线粒体以及人血影为对象,研究了3β,5α,6β-三羟胆固醇(Triol)对线粒体的氧化损伤作用,及其产生氧化损伤的可能机制。主要研究结果如下:
1.研究了Triol对分离的小鼠肝线粒体的氧化损伤作用,包括脂质过氧化、膜蛋白氧化、H2O2产生、跨膜电位、细胞色素C释放等。结果表明,Triol能引起肝线粒体脂质过氧化和膜蛋白的氧化程度增强、H2O2水平升高,并引起跨膜电位降低以及细胞色素C的释放增加。
2.测定了Triol对线粒体内膜上呼吸链部分酶活性的影响。结果显示,Triol作用分离的小鼠肝线粒体能引起线粒体呼吸链上复合物Ⅰ和Ⅱ酶活性升高,对复合物Ⅲ酶活性无显著影响。而Triol作用破碎后的线粒体,引起复合物Ⅰ和复合物Ⅲ酶活性降低以及复合物Ⅱ酶活性升高。
3.应用衰减全反射-傅立叶红外技术,以人血影为模型,研究了Triol对质膜的作用。结果表明,Triol使血影膜蛋白α-螺旋结构含量升高、β-折叠和β-转角含量降低、无规卷曲含量略有降低;随着作用时间的延长,Triol对α-螺旋结构、无规卷曲以及β-转角含量的影响均更加显著,而β-折叠含量在Triol作用时间延长时反而逐渐升高。
Atherosclerosis (AS) is one of the most serious diseases in human, and the cholesterol oxidation products (Ch-Ox) are currently considered as a key atherogenic factor in its pathogenesis. The researches on the cytotoxicity of Ch-Ox and its mechanism, the prevention and cure of AS are one of the frontier fields in human health.
In this paper, the effect of Triol on oxidative impairment of isolated mouse liver mitochondria and the probable mechanism were investigated. The main results are as follows:
1. The effect of Cholestane-3β, 5α, 6β-triol(Triol) on lipid peroxidation, membrane protein oxidation, H2O2 generation, transmembrane potential, release of cytochorme c of isolated mouse liver mitochondria were studied. The results indicated that Triol induced lipid peroxidation and membrane protein oxidation, decrease of transmembrane potential, and increase of H2O2 generation and cytochorme C release.
2. To further investigate the mechanism, the effects of Triol on the activity of three enzymes in mitochondria respiratory chain were studied. The results suggested that complex I and II enzyme activity increased, while complex III enzyme activity did not change significantly as Triol applied to intact mitochondria. Furthermore, complex I and III enzyme activity decreased, and complex II enzyme activity increased as Triol applied to broken mitochondria.
3. The effect of Triol on membrane protein secondary structure of human ghost was studied by Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR- FTIR). The results showed thatα-helix increased dose- and time-dependently, andβ-sheet decreased at high concentration of Triol but increased as time prolonged, and random as well as turns reduced dose- and time-dependently.
本论文以分离的小鼠肝线粒体以及人血影为对象,研究了3β,5α,6β-三羟胆固醇(Triol)对线粒体的氧化损伤作用,及其产生氧化损伤的可能机制。主要研究结果如下:
1.研究了Triol对分离的小鼠肝线粒体的氧化损伤作用,包括脂质过氧化、膜蛋白氧化、H2O2产生、跨膜电位、细胞色素C释放等。结果表明,Triol能引起肝线粒体脂质过氧化和膜蛋白的氧化程度增强、H2O2水平升高,并引起跨膜电位降低以及细胞色素C的释放增加。
2.测定了Triol对线粒体内膜上呼吸链部分酶活性的影响。结果显示,Triol作用分离的小鼠肝线粒体能引起线粒体呼吸链上复合物Ⅰ和Ⅱ酶活性升高,对复合物Ⅲ酶活性无显著影响。而Triol作用破碎后的线粒体,引起复合物Ⅰ和复合物Ⅲ酶活性降低以及复合物Ⅱ酶活性升高。
3.应用衰减全反射-傅立叶红外技术,以人血影为模型,研究了Triol对质膜的作用。结果表明,Triol使血影膜蛋白α-螺旋结构含量升高、β-折叠和β-转角含量降低、无规卷曲含量略有降低;随着作用时间的延长,Triol对α-螺旋结构、无规卷曲以及β-转角含量的影响均更加显著,而β-折叠含量在Triol作用时间延长时反而逐渐升高。
Atherosclerosis (AS) is one of the most serious diseases in human, and the cholesterol oxidation products (Ch-Ox) are currently considered as a key atherogenic factor in its pathogenesis. The researches on the cytotoxicity of Ch-Ox and its mechanism, the prevention and cure of AS are one of the frontier fields in human health.
In this paper, the effect of Triol on oxidative impairment of isolated mouse liver mitochondria and the probable mechanism were investigated. The main results are as follows:
1. The effect of Cholestane-3β, 5α, 6β-triol(Triol) on lipid peroxidation, membrane protein oxidation, H2O2 generation, transmembrane potential, release of cytochorme c of isolated mouse liver mitochondria were studied. The results indicated that Triol induced lipid peroxidation and membrane protein oxidation, decrease of transmembrane potential, and increase of H2O2 generation and cytochorme C release.
2. To further investigate the mechanism, the effects of Triol on the activity of three enzymes in mitochondria respiratory chain were studied. The results suggested that complex I and II enzyme activity increased, while complex III enzyme activity did not change significantly as Triol applied to intact mitochondria. Furthermore, complex I and III enzyme activity decreased, and complex II enzyme activity increased as Triol applied to broken mitochondria.
3. The effect of Triol on membrane protein secondary structure of human ghost was studied by Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR- FTIR). The results showed thatα-helix increased dose- and time-dependently, andβ-sheet decreased at high concentration of Triol but increased as time prolonged, and random as well as turns reduced dose- and time-dependently.
引文
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