本文關(guān)鍵詞： 硒 長(zhǎng)雙歧桿菌 富硒長(zhǎng)雙歧桿菌 CTX 腫瘤 藥代動(dòng)力學(xué)　出處：《南京大學(xué)》2014年碩士論文　論文類(lèi)型：學(xué)位論文

【摘要】：硒元素是人體必需的微量元素之一。機(jī)體硒水平與癌癥發(fā)生率呈負(fù)相關(guān),補(bǔ)硒能有效抑制腫瘤的發(fā)生。但是,以亞硒酸鹽為主的無(wú)機(jī)硒有較大的毒性,且不易被吸收,不適合人和動(dòng)物長(zhǎng)期使用。雙歧桿菌能夠選擇性的富集到腫瘤組織的無(wú)氧區(qū),具有高度的靶向性,且雙歧桿菌是人體內(nèi)固有的有益菌,沒(méi)有致病性,可以作為富集和轉(zhuǎn)化硒的載體。本實(shí)驗(yàn)中,我們證實(shí)了硒能在長(zhǎng)雙歧桿菌中富集并評(píng)估了富硒長(zhǎng)雙歧桿菌對(duì)腫瘤生長(zhǎng)以及荷瘤小鼠免疫功能的影響。利用高效液相色譜-電感耦合等離子質(zhì)譜法分析,發(fā)現(xiàn)富硒長(zhǎng)雙歧桿菌中有機(jī)硒含量超過(guò)99%,有機(jī)硒的主要成分為硒代蛋氨酸(SeMet)。體內(nèi)實(shí)驗(yàn)表明,三種劑量的Se-B.longum灌胃給藥后,無(wú)論單獨(dú)還是與環(huán)磷酰胺(CTX)聯(lián)合使用,中劑量和高劑量的Se-B.longum均能顯著性抑制腫瘤的生長(zhǎng),且與CTX聯(lián)合使用后,腫瘤抑制效果顯著提高并且能夠顯著性延長(zhǎng)荷瘤小鼠的存活時(shí)間。此外,Se-B.longum與CTX聯(lián)用后可以有效提高其免疫功能、提高NK細(xì)胞和T淋巴細(xì)胞的活性、增加IL-2以及TNF-α的水平并能增加白細(xì)胞數(shù),從而降低CTX治療產(chǎn)生的毒性。此外,本實(shí)驗(yàn)還分別考察了硒雙歧桿菌的主要成分硒和長(zhǎng)雙歧桿菌在動(dòng)物體內(nèi)的藥代動(dòng)力學(xué)特征。不同劑量的硒雙歧桿菌經(jīng)Beagle犬灌胃后,原子熒光法分別測(cè)定給藥后不同時(shí)間點(diǎn)血液中的硒含量、硒的組織分布及排泄。結(jié)果表明,在一定的劑量范圍內(nèi),血液中的硒含量變化不明顯,不能計(jì)算藥代動(dòng)力學(xué)參數(shù)；給藥后2 h,硒主要分布的肝臟和腎臟；在動(dòng)物的排泄物中未檢測(cè)到硒元素。不同劑量的硒雙歧桿菌經(jīng)小鼠灌胃后,研究小鼠腸道菌群的變化及長(zhǎng)雙歧桿菌在腸道中的定植情況。結(jié)果表明,硒雙歧桿菌可以調(diào)節(jié)腸道的菌群數(shù)量和結(jié)構(gòu)；長(zhǎng)雙歧桿菌主要定植在小鼠的盲腸部位；給藥后12h,雙歧桿菌已大部分定植；給藥后1d和7d,雙歧桿菌的數(shù)量逐漸增加,且停藥后3d雙歧桿菌數(shù)量并沒(méi)有減少。
[Abstract]:Selenium is one of the essential trace elements in human body. The level of selenium in body is negatively correlated with the incidence of cancer. Selenium supplementation can effectively inhibit the occurrence of tumor. However, inorganic selenium, which is mainly selenite, is toxic and is not easily absorbed. Bifidobacterium can be selectively enriched into the anaerobic region of tumor tissue and has a high targeting. Bifidobacterium is a beneficial bacterium inherent in the human body and has no pathogenicity. It can be used as a carrier for the enrichment and transformation of selenium. We confirmed that selenium can be enriched in Bifidobacterium longifera and evaluated the effect of Bifidobacterium selenium-enriched on tumor growth and immune function in tumor-bearing mice. The results were analyzed by high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS). It was found that the content of organic selenium in Bifidobacterium selenium-enriched was more than 990.The main component of organic selenium was selenomethionine SeMet.Invivo experiments showed that three doses of Se-B.longum were used either alone or in combination with cyclophosphamide (CTX). Both middle and high doses of Se-B.longum could significantly inhibit the growth of tumor, and combined with CTX could inhibit the growth of tumor. In addition, the combination of Se-B.longum and CTX could effectively improve the immune function and the activity of NK cells and T lymphocytes. Increase the levels of IL-2 and TNF- 偽 and increase the number of white blood cells, thereby reducing the toxicity of CTX therapy. The pharmacokinetic characteristics of selenium bifidobacterium and bifidobacterium longifera in animals were also investigated. Different doses of selenium bifidobacterium were fed by Beagle dogs. The content of selenium in blood, tissue distribution and excretion of selenium were determined by atomic fluorescence method at different time points after administration. The results showed that the changes of selenium content in blood were not obvious within a certain dose range, and the pharmacokinetic parameters could not be calculated. At 2 hours after administration, selenium was mainly distributed in liver and kidney, and selenium was not detected in animal excreta. The changes of intestinal flora in mice and the colonization of bifidobacterium longus in intestinal tract were studied. The results showed that Bifidobacterium selenoides could regulate the number and structure of intestinal flora, and that Bifidobacterium longifera was mainly located in the cecum of mice. Bifidobacterium was mostly colonized 12 hours after administration, and the number of bifidobacterium increased gradually at 1 and 7 days after administration, and the number of bifidobacterium did not decrease 3 days after drug withdrawal.
【學(xué)位授予單位】：南京大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R965

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