过氧亚硝酸根在二氧化碳仿生环境中的毒理性质研究
发布时间：2018-12-14 00:37
【摘要】：一氧化氮自由基（NO）和超氧阴离子（O_2~-）快速结合会生成一种具有强氧化、硝化能力的细胞毒性物质——过氧亚硝酸根（ONOO~-），ONOO-能引起多种生物大分子损伤，可硝化蛋白质酪氨酸残基、诱导DNA链断裂以及促进脂质过氧化反应，导致细胞凋亡等，，进而引发一系列重大疾病的产生。然而体内环境中含有大量的重碳酸盐（25mM左右），与二氧化碳处于动态平衡，二氧化碳与过氧亚硝酸根反应从而影响过氧亚硝酸根的毒理学性质。本文应用紫外-可见分光光度计、流动注射分析仪和高效液相色谱等分析仪器，结合体内微环境，研究了过氧亚硝酸根在二氧化碳仿生环境中的自分解、损伤生物分子及其清除等毒理性质，主要内容包括以下3个方面： 1、过氧亚硝酸根的自分解以及二氧化碳对其分解的动力学分析 过氧亚硝酸根的自分解属于一级反应。当温度为37℃、盐离子浓度为0.1M时，过氧亚硝酸根在pH为7.4时的降解速率k=1.0s~(-1)。采用拟一级反应动力学方法，研究了过氧亚硝酸根与二氧化碳反应的动力学。在中性条件、盐离子浓度为0.1M、温度37℃下，过氧亚硝酸根与二氧化碳反应的速率常数k=2.3×10~3M~(-1)s~(-1)。 2、二氧化碳对过氧亚硝酸损伤酪氨酸和色氨酸影响的研究 反应体系中二氧化碳的存在可抑制过氧亚硝酸根对色氨酸和酪氨酸的损伤。通过高效液相色谱分析，当反应体系中含有碳酸氢盐时，过氧亚硝酸根损伤氨基酸的产物浓度低于反应体系中无二氧化碳存在时的产物浓度，说明二氧化碳能够减少过氧亚硝酸根的生物毒性。推测认为当体系中含有碳酸氢盐时，过氧亚硝酸根首先与碳酸氢盐释放的二氧化碳发生反应，生成加合物ONO_2CO_2~-，该物质会进一步裂解产生硝基自由基和碳酸氢根自由基，对氨基酸产生硝化和氧化作用。 3、二氧化碳对卟啉催化过氧亚硝酸根的动力学分析 利用流动注射分析仪研究了二氧化碳对铁卟啉催化过氧亚硝酸根分解的动力学影响，结果证明，体系中的二氧化碳可加快铁卟啉催化过氧亚硝酸根分解的速率，在生理条件下，体系中有无二氧化碳时，卟啉催化过氧亚硝酸根分解的催化速率常数分别为1.26×10~6M~(-1)s~(-1)和1.17×10~6M~(-1)s~(-1)。 该研究考虑了重碳酸盐在人体内环境中大量存在这一事实，模拟体内微环境，能够更准确的反应过氧亚硝酸根在人体中的毒理性质，对过氧亚硝酸根引起的相关疾病具有预防和治疗的作用，对保护人体健康具有积极意义。
[Abstract]:The rapid combination of nitric oxide free radical (NO) and superoxide anion produces a cytotoxic substance with strong oxidation and nitrification, peroxynitrite (ONOO~-). ONOO- can cause damage to many biological macromolecules. Nitrifying protein tyrosine residues induce DNA strand breakage and promote lipid peroxidation, leading to apoptosis and leading to a series of major diseases. However, there is a large amount of bicarbonates (about 25mM) in the body, which is in dynamic equilibrium with carbon dioxide. The reaction of carbon dioxide with peroxynitrite affects the toxicological properties of peroxynitrite. In this paper, the self-decomposition of peroxynitrite in the bionic environment of carbon dioxide was studied by means of UV-Vis spectrophotometer, flow injection analyzer and high performance liquid chromatography. The toxicological properties of damaged biomolecules and their clearance include the following three aspects: 1. Self-decomposition of peroxynitrite and kinetic analysis of its decomposition by carbon dioxide the self-decomposition of peroxynitrite is a first-order reaction. When the temperature is 37 鈩
本文编号：2377555
[Abstract]:The rapid combination of nitric oxide free radical (NO) and superoxide anion produces a cytotoxic substance with strong oxidation and nitrification, peroxynitrite (ONOO~-). ONOO- can cause damage to many biological macromolecules. Nitrifying protein tyrosine residues induce DNA strand breakage and promote lipid peroxidation, leading to apoptosis and leading to a series of major diseases. However, there is a large amount of bicarbonates (about 25mM) in the body, which is in dynamic equilibrium with carbon dioxide. The reaction of carbon dioxide with peroxynitrite affects the toxicological properties of peroxynitrite. In this paper, the self-decomposition of peroxynitrite in the bionic environment of carbon dioxide was studied by means of UV-Vis spectrophotometer, flow injection analyzer and high performance liquid chromatography. The toxicological properties of damaged biomolecules and their clearance include the following three aspects: 1. Self-decomposition of peroxynitrite and kinetic analysis of its decomposition by carbon dioxide the self-decomposition of peroxynitrite is a first-order reaction. When the temperature is 37 鈩
本文编号：2377555
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