本文選題：抗生素混合物 + 均勻設(shè)計(jì)射線法　； 參考：《安徽建筑大學(xué)》2016年碩士論文

【摘要】：抗生素是由微生物(包括細(xì)菌、真菌、放線菌屬等)或高等動(dòng)植物在生活過(guò)程中所產(chǎn)生的一類具有抵抗微生物活性的天然、半合成或人工合成化合物。按化學(xué)結(jié)構(gòu)分,可分為氨基糖苷類、β-內(nèi)酰胺類、四環(huán)素類、喹諾酮類、大環(huán)內(nèi)酯類、多肽類、酰胺醇類、林可酰胺類等�？股刂饕糜陬A(yù)防和治療人類和動(dòng)物疾病,后來(lái)也作為一種生長(zhǎng)促進(jìn)劑添加在飼料中促進(jìn)動(dòng)物的生長(zhǎng)發(fā)育。然而,由于抗生素的大量生產(chǎn)和嚴(yán)重的濫用現(xiàn)象,一部分不可被人畜機(jī)體吸收利用的抗生素進(jìn)入環(huán)境頻度高,對(duì)生態(tài)平衡和生物體造成危害。實(shí)際環(huán)境中的污染物普遍具有低劑量和混合暴露的特征,污染物隨暴露時(shí)間的延長(zhǎng)具有不同的毒性變化規(guī)律。因此,對(duì)環(huán)境中相關(guān)抗生素及其混合物的時(shí)間依賴毒性評(píng)估具有重要的現(xiàn)實(shí)意義。本文針對(duì)抗生素及其混合物在不同暴露時(shí)間具有不同的毒性變化規(guī)律的現(xiàn)象,以蛋白核小球藻作為指示生物,以20種不同類型的抗生素作為目標(biāo)化合物,采用時(shí)間依賴微板毒性分析法測(cè)定了它們?cè)?0、12、24、48、72和96 h)6個(gè)不同時(shí)間下的毒性。運(yùn)用兩階段模型法評(píng)估混合物的時(shí)間依賴毒性,根據(jù)單個(gè)抗生素的時(shí)間依賴毒性測(cè)試結(jié)果,應(yīng)用均勻設(shè)計(jì)射線法設(shè)計(jì)每類抗生素的五元混合物體系共28條射線和20種抗生素的多元混合體系15條射線,考察它們的時(shí)間毒性變化規(guī)律。本文的主要內(nèi)容與成果總結(jié)如下:(1)20種抗生素在48~96h具有良好的濃度-響應(yīng)關(guān)系,不同抗生素的毒性隨時(shí)間變化的規(guī)律不同:大部分抗生素的毒性隨時(shí)間延長(zhǎng)而顯著增加,妥布霉素在前4個(gè)時(shí)間點(diǎn)內(nèi)幾乎沒(méi)有毒性,然后毒性隨時(shí)間延長(zhǎng)而顯著增加;哌拉西林鈉、氨芐西林鈉和恩諾沙星的毒性隨時(shí)間延長(zhǎng)先增加再減小;鹽酸金霉素、鹽酸強(qiáng)力霉素、美他環(huán)素和鹽酸四環(huán)素的毒性隨時(shí)間延長(zhǎng)先減小再增加,諾氟沙星幾乎沒(méi)有毒性。(2)4組五元混合物28條射線和3組多元混合物15條射線在各時(shí)間點(diǎn)具有良好的濃度-響應(yīng)關(guān)系,且具有時(shí)間依賴性,但不同混合物體系的毒性變化規(guī)律不同:如氨基糖苷類抗生素混合物有的隨時(shí)間延長(zhǎng)毒性逐漸增強(qiáng),有的開(kāi)始具有hormesis效應(yīng),隨時(shí)間逐漸減弱;β-內(nèi)酰胺類抗生素幾乎沒(méi)有明顯的毒性,而是具有明顯的hormesis效應(yīng),其它兩組混合體系的毒性隨時(shí)間延長(zhǎng)逐漸增加;五元混合物體系的毒性與混合物中某組分濃度比pi之間有較好的線性關(guān)系。(3)以濃度加和作用模型CA為參考模型,五元混合物毒性基本上呈加和作用,以IA為參考模型,發(fā)現(xiàn)部分20種抗生素的混合物毒性偏離了IA模型出現(xiàn)了協(xié)同或拮抗作用,具有濃度依賴性和時(shí)間依賴性�？傊�,除了呈現(xiàn)出hormesis效應(yīng)、協(xié)同或拮抗作用的抗生素混合物,兩階段模型能較好地評(píng)估大多數(shù)抗生素混合物的時(shí)間依賴毒性。
[Abstract]:Antibiotics are natural, semi-synthetic or synthetic compounds produced by microorganisms (including bacteria, fungi, actinomycetes, etc.) or higher plants and animals during their life. According to the chemical structure, it can be divided into aminoglycosides, 尾-lactams, tetracyclines, quinolones, macrolides, polypeptides, amides, lincomides, etc. Antibiotics are mainly used in the prevention and treatment of human and animal diseases, and later as a growth promoter to promote the growth and development of animals. However, due to the large production of antibiotics and serious abuse, some antibiotics which can not be absorbed and used by human and animal organisms have a high frequency of entry into the environment, which is harmful to ecological balance and organisms. The pollutants in the real environment generally have the characteristics of low dose and mixed exposure, and the pollutants have different toxic changes with the prolongation of exposure time. Therefore, time dependent toxicity assessment of related antibiotics and their mixtures in the environment is of great practical significance. In view of the phenomenon that antibiotics and their mixtures have different toxic changes at different exposure time, Chlorella Proteinuca is used as indicator organism and 20 different types of antibiotics as target compounds. Time dependent microplate toxicity analysis was used to determine their toxicity at 6 different time periods. A two-stage model was used to assess the time-dependent toxicity of the mixture, based on the results of the time-dependent toxicity tests for individual antibiotics. In this paper, a uniform design ray method was used to design a mixture system of 28 rays and 20 kinds of antibiotics in a five-component mixture system of each antibiotic, and 15 rays were used to investigate their temporal toxicity. The main contents and results of this paper are summarized as follows: 20 kinds of antibiotics have a good dose-response relationship at 48 ~ 96h. The toxicity of different antibiotics varies with time: the toxicity of most antibiotics increases significantly with time. Tobramycin had little toxicity at the first four time points and then increased significantly with time; the toxicity of piperacillin sodium, ampicillin sodium and enrofloxacin increased first and then decreased with time; chlortetracycline hydrochloride, chlortetracycline hydrochloride, The toxicity of doxycycline hydrochloride, metacycline and tetracycline hydrochloride decreases first and then increases over time. The toxicity of norfloxacin was almost non-toxic. The five-component mixture of four groups (28 rays) and the multicomponent mixture of 3 groups (15 rays) had a good concentration-response relationship at each time point and were time-dependent. However, the toxicity changes of different mixtures are different: for example, the toxicity of aminoglycoside antibiotic mixtures increases gradually with time, and some of them begin to have hormesis effect. 尾-lactam antibiotics had no obvious toxicity, but had obvious hormesis effect, and the toxicity of the other two groups increased gradually with the prolongation of time. There is a good linear relationship between the toxicity of the five-element mixture system and the concentration of a certain component in the mixture than pi. The reference model is CA. The toxicity of the five-element mixture is basically additive, and IA is the reference model. It was found that the toxicity of some of the 20 antibiotics deviated from the IA model and had synergistic or antagonistic effects in a concentration-and time-dependent manner. In a word, in addition to the mixture of antibiotics with hormesis effect, synergistic or antagonistic effect, the two-stage model can better evaluate the time-dependent toxicity of most antibiotic mixtures.
【學(xué)位授予單位】：安徽建筑大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：X171.5

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