具有清除羥自由基能力的GPX模擬物的研究
發(fā)布時間：2018-11-19 13:54
【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、分子量大等缺點限制了它的藥用前景。因此,人們把注意力集中在對它的人工模擬上。我室利用環(huán)糊精空腔作為底物結(jié)合口袋、二碲橋為催化中心合成出含咪唑的環(huán)糊精衍生物6-ImTeCD,用來模擬GPX。實驗結(jié)果表明該模擬物具有較高的GPX活力,且催化機制、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胞的模型,細胞表現(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的加入降低了細胞內(nèi)MDA生成量、提高了損傷細胞存活率、預(yù)防了細胞內(nèi)LDH的泄漏,使細胞膜能夠保持良好的通透性,很好地保護了肝細胞,使其免受氧化損傷。另外,6-ImTeCD能夠穿過細胞膜進入肝細胞中,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)位級別】：碩士
【學(xué)位授予年份】：2008
【分類號】：R341
本文編號：2342505
[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)位級別】：碩士
【學(xué)位授予年份】：2008
【分類號】：R341
【參考文獻】
相關(guān)期刊論文 前1條
1 尤長城,劉育;超分子體系中的分子識別研究(一)——有機硒修飾β-環(huán)糊精的合成及其與L-和D-色氨酸的包結(jié)配位作用[J];高等學(xué)�；瘜W(xué)學(xué)報;2000年02期
，本文編號：2342505
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