本文選題：頭孢菌素 + 重金屬離子�。� 參考：《湖北師范大學(xué)》2017年碩士論文

【摘要】：抗生素對(duì)多數(shù)常見(jiàn)菌抑制效果良好。在日常生活中,抗生素常被用來(lái)治療因細(xì)菌感染而引發(fā)的多種疾病;有些畜牧養(yǎng)殖廠為預(yù)防牲畜細(xì)菌感染而大面積使用抗生素;有些不法商家甚至使用抗生素促使牲畜快速生長(zhǎng),危害巨大。人體、牲畜使用的抗生素在體內(nèi)吸收往往不完全,會(huì)隨代謝產(chǎn)物排出體外,與大量過(guò)期的抗生素一起流入環(huán)境體系,破壞生態(tài)環(huán)境。頭孢菌素類抗生素種類繁多,對(duì)大多數(shù)細(xì)菌(如革蘭氏陰或陽(yáng)性菌)所引發(fā)的細(xì)菌感染均有良好的抑菌作用。頭孢菌素最常用的分類方法為依據(jù)抗菌特點(diǎn)而分類,分為四代,其種類居各類抗生素首位,且不同頭孢菌素分子結(jié)構(gòu)之間存在較大差異。工業(yè)生產(chǎn)產(chǎn)生的重金屬離子,經(jīng)水體、土壤、大氣的傳遞與運(yùn)輸,廣泛分布在環(huán)境中。具有強(qiáng)遺傳毒性的重金屬離子危害極大,一旦進(jìn)入食物鏈,即使經(jīng)過(guò)多層食物鏈的傳遞也無(wú)法從生物體內(nèi)代謝除去,從而不間斷地在重要器官內(nèi)吸附、積累,嚴(yán)重威脅人類和動(dòng)物健康。本文旨在利用生物化學(xué)方法,對(duì)比研究分子結(jié)構(gòu)上差異性較大的頭孢菌素與生物大分子的親和作用,考察頭孢菌素分子母核側(cè)鏈連接不同基團(tuán)對(duì)頭孢菌素-生物大分子親和作用所造成的影響,進(jìn)而分析頭孢菌素分子結(jié)構(gòu)-親和性對(duì)應(yīng)關(guān)系。引入強(qiáng)遺傳毒性重金屬離子,考察重金屬離子與頭孢菌素之間的協(xié)同效應(yīng)。本論文共分為五章,分別為:第一章:主要介紹了現(xiàn)今環(huán)境中普遍存在的抗生素以及重金屬離子,分別闡述抗生素與重金屬離子的使用、排放以及污染現(xiàn)狀;歸納現(xiàn)今用作分析藥物小分子-生物大分子相互作用的主要研究方法,概括研究現(xiàn)狀;從總體研究思路,文章立題意義,以及本文研究特點(diǎn)等方面概述。第二章:以頭孢克洛(第二代頭孢菌素)、頭孢克肟(第三代頭孢菌素)為研究對(duì)象,采用紫外吸收光譜、熒光光譜、分子模擬技術(shù)、電化學(xué)方法考察這兩種頭孢菌素與生物大分子DNA相互作用時(shí)的作用機(jī)理、結(jié)合模式。研究抗生素分子結(jié)構(gòu)-作用機(jī)理之間的關(guān)聯(lián)。同時(shí)考察溫度、離子強(qiáng)度、變性劑、熱變性、作用時(shí)間、重金屬離子等因素對(duì)頭孢菌素與DNA相互作用的影響。第三章:借助紫外吸收光譜、熒光光譜、分子模擬等方法研究頭孢氨芐(第一代頭孢菌素)、頭孢克肟(第三代頭孢菌素)與牛血清白蛋白的相互作用。比較并分析實(shí)驗(yàn)中所引入的兩種頭孢菌素分子結(jié)構(gòu)上存在的差異;比較相互作用機(jī)理;判斷主要作用力;確定結(jié)合位點(diǎn);分析所加藥物對(duì)氨基酸殘基所處微環(huán)境的影響;實(shí)驗(yàn)中選用計(jì)算機(jī)輔助設(shè)計(jì),從分子結(jié)構(gòu)角度深入考察作用體系具體鍵聯(lián)信息;同時(shí),選擇性添加重金屬離子,分析其對(duì)頭孢克洛(或頭孢克肟)與牛血清白蛋白親和作用的影響。第四章:選取四種頭孢菌素(頭孢氨芐、頭孢克洛、頭孢克肟以及頭孢吡肟),選用光分析方法、電分析方法、以及分子模擬方法分析四種頭孢菌素與人血清白蛋白的相互作用。對(duì)比實(shí)驗(yàn)中所引入的四種頭孢菌素分子結(jié)構(gòu)上所存在的差異;判斷作用機(jī)理;確定主要作用力;確定結(jié)合位點(diǎn);選用交流阻抗法考察反應(yīng)體系電子的轉(zhuǎn)移情況,并深入探究電子發(fā)生轉(zhuǎn)移原因;實(shí)驗(yàn)中選用圓二色光譜、三維熒光光譜、同步熒光光譜法分析這四種頭孢菌素的加入對(duì)蛋白質(zhì)分子空間構(gòu)象的影響;考察具有強(qiáng)遺傳毒性的重金屬離子與頭孢菌素之間的協(xié)同效應(yīng);同時(shí)結(jié)合分子模擬技術(shù),深入考察四種頭孢菌素與人血清白蛋白結(jié)合的具體鍵聯(lián)信息。第五章:總結(jié)全文并得出實(shí)驗(yàn)結(jié)論,展望后續(xù)工作,為頭孢菌素結(jié)構(gòu)-親和性研究提出思考和建議。
[Abstract]:Antibiotics have a good effect on most common bacteria. In daily life, antibiotics are often used to treat a variety of diseases caused by bacterial infection; some livestock farms use antibiotics for the prevention of bacterial infection in livestock. Some illegal businesses even use antibiotics to promote rapid growth of livestock. The antibiotics used in the body are often not completely absorbed in the body. They will be discharged in vitro with the metabolites and flow into the environment system with a large number of overexpired antibiotics and destroy the ecological environment. There are a wide variety of cephalosporins, which have good bacteriostasis for the bacterial infection caused by most bacteria (such as gram-negative or positive bacteria). The most commonly used classification method is classified into four generations according to the characteristics of antibacterial activity, and its species ranks first in various kinds of antibiotics, and there are great differences between different molecular structures of cephalosporins. Heavy metal ions produced by industrial production are widely distributed in the environment through the transmission and transportation of water, soil and atmosphere. Heavy metals with strong genetic toxicity are found in the environment. Once entering the food chain, even through the food chain, even through the transmission of the multi-layer food chain, it can not be removed from the organism, thus uninterruptedly adsorbing, accumulating and threatening human and animal health in an important organ. This paper aims to use biochemical methods to compare and study cephalosporins with large differences in molecular structure. The influence of different groups of cephalosporins on the affinity of cephalosporins and biological macromolecules by the side chain of cephalosporins was investigated, and the corresponding relationship between the molecular structure and affinity of cephalosporins was analyzed. The strong genotoxic heavy metal ions were introduced to investigate the synergistic effect between heavy metal ions and cephalosporins. This paper is divided into five chapters: Chapter 1: the first chapter is the introduction of the prevailing antibiotics and heavy metal ions in the present environment. The use, emission and pollution status of antibiotics and heavy metal ions are described respectively, and the main research methods used to analyze the interaction of small molecules and macromolecules are summarized and summarized. The second chapter: using cefaclor (second generation cephalosporins) and cefixime (third generation cephalosporins) as the research object, using UV absorption spectra, fluorescence spectra, molecular simulation technology and electrochemical methods to investigate the two cephalosporins and biological fractions. The interaction mechanism of the sub DNA interaction, combined with the mode. The relationship between the molecular structure of antibiotics and the mechanism of action. The influence of temperature, ionic strength, denaturant, thermal denaturation, action time, heavy metal ions on the interaction of cephalosporin and DNA. The third chapter: UV absorption, fluorescence, molecular simulation To study the interaction between cefamoxin (first generation cephalosporin) and cefixime (third generation cephalosporins) and bovine serum albumin. Compare and analyze the differences in the molecular structure of the two kinds of cephalosporins introduced in the experiment; compare the interaction mechanism; determine the main force; determine the binding site; analyze the added drugs to ammonia. The effect of the microenvironment on the base acid residues; in the experiment, the computer aided design was selected to examine the specific bond information from the molecular structure angle. At the same time, the effect of the selective addition of heavy metal ions on the affinity and effect of cefaclor (or cefixime) with bovine serum albumin was analyzed. The fourth chapter: the selection of four cephalosporins (head) The interaction between four cephalosporins and human serum albumin was analyzed by PHOTOANALYSIS, electroanalysis and molecular simulation. The differences in the molecular structure of the four cephalosporins introduced in the experiment were compared, the mechanism of action was judged and the main force was determined. To determine the binding site, use the AC impedance method to investigate the electron transfer in the reaction system, and to explore the cause of the electron transfer. In the experiment, the effect of the four cephalosporins on the spatial conformation of the protein molecules was analyzed by using the circular two color spectrum, the three-dimensional fluorescence spectrum and the synchronous fluorescence spectrum, and the strong genotoxicity was investigated. The synergistic effect between heavy metal ions and cephalosporins; at the same time combined with molecular simulation technology, the specific bond information of the binding of four cephalosporins to human serum albumin was examined in depth. The fifth chapter: summarize the full text and draw the conclusion of the experiment, and look forward to the follow-up work, and put forward some thoughts and suggestions for the study of cephalosporin's structure and affinity.
【學(xué)位授予單位】：湖北師范大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R96

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本文編號(hào)：1968408