【摘要】： 谷胱甘肽過氧化物酶(GPX)是生物體內(nèi)重要的抗氧化酶,能有效地清除活性氧自由基,但是此酶來源有限、穩(wěn)定性差、分子量大等缺點(diǎn)限制了它的藥用前景。因此,人們把注意力集中在對(duì)它的人工模擬上。我室利用環(huán)糊精空腔作為底物結(jié)合口袋、二碲橋?yàn)榇呋行暮铣沙龊溥虻沫h(huán)糊精衍生物6-ImTeCD,用來模擬GPX。實(shí)驗(yàn)結(jié)果表明該模擬物具有較高的GPX活力,且催化機(jī)制、最適pH值和最適溫度均與天然酶相似。6-ImTeCD的加入可使羅丹明B分子免受羥自由基的破壞,證明了該模擬酶具有預(yù)期的雙重抗氧化損傷能力。建立過氧化氫損傷肝細(xì)胞的模型,細(xì)胞表現(xiàn)出脂質(zhì)過氧化損傷,且損傷程度與過氧化氫濃度存在劑量依賴性,6-ImTeCD的加入降低了細(xì)胞內(nèi)MDA生成量、提高了損傷細(xì)胞存活率、預(yù)防了細(xì)胞內(nèi)LDH的泄漏,使細(xì)胞膜能夠保持良好的通透性,很好地保護(hù)了肝細(xì)胞,使其免受氧化損傷。另外,6-ImTeCD能夠穿過細(xì)胞膜進(jìn)入肝細(xì)胞中,使該分子極有可能成為預(yù)防和治療由ROS介導(dǎo)的疾病的藥物前體。
[Abstract]:Glutathione peroxidase (GPX) is an important antioxidant enzyme which can effectively scavenge reactive oxygen free radicals. However, its limited sources, poor stability and high molecular weight limit its medicinal prospects. Therefore, attention is focused on the artificial simulation of it. A cyclodextrin derivative 6-ImTeCD-containing imidazolium was synthesized by using cyclodextrin cavity as substrate binding pocket and tellurium bridge as catalytic center in our room, which was used to simulate GPX.. The experimental results show that the mimic has high GPX activity, and its catalytic mechanism, optimum pH value and optimum temperature are similar to those of natural enzymes. The addition of 6-ImTeCD can protect Rhodamine B from the destruction of hydroxyl radical. It is proved that the mimic enzyme has the expected ability of double antioxidant damage. The model of hydrogen peroxide injury of hepatocytes was established. The cells showed lipid peroxidation damage in a dose-dependent manner. The addition of 6-ImTeCD decreased the MDA production and increased the survival rate of the injured cells. It can prevent the leakage of intracellular LDH, keep the membrane permeability and protect hepatocytes from oxidative damage. In addition, 6-ImTeCD can penetrate the cell membrane into the hepatocytes, making the molecule a potential drug precursor for the prevention and treatment of ROS-mediated diseases.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2008
【分類號(hào)】：R341

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