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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 高照村 | |
| dc.contributor.author | Yuan-Ting Lee | en |
| dc.contributor.author | 李媛婷 | zh_TW |
| dc.date.accessioned | 2021-06-13T01:15:48Z | - |
| dc.date.available | 2008-08-08 | |
| dc.date.copyright | 2007-08-08 | |
| dc.date.issued | 2007 | |
| dc.date.submitted | 2007-07-19 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/29711 | - |
| dc.description.abstract | 脂蛋白解脂酶 (LPL) 在脂質代謝方面佔有重要的角色，其主要的功能在於水解乳糜微粒和極低密度脂蛋白中的三酸甘油酯。三酸甘油酯經脂蛋白解脂酶分解會形成游離型脂肪酸及甘油，而游離型脂肪酸可燃燒作為能量使用，或者以脂肪形式貯存。當脂蛋白解脂酶發生變異時會造成第一型高脂血症，脂質的代謝會失去平衡。
本實驗室在先前的研究中，從台灣地區高三酸甘油酯血症病人血液中發現了脂蛋白解脂酶兩處基因突變，分別是在第252位置的白胺酸變成精胺酸和纈胺酸。這兩處基因的突變皆會造成高三酸甘油酯血症。為了想治療這兩處的基因突變造成的高三酸甘油酯血症，擬建構包含人類脂蛋白解脂酶啟動子序列及cDNA的質體，分別是野生型PLPLWT及突變型PLPL252R和PLPL252V，將這些質體分別轉染到人類293細胞後再藉由藥物（bezafibrate, ciprofibrate, fenofibrate, gemfibrozil, curcumin, esculetin）處理，觀察看是否能達到提高LPL活性及濃度之效用，藉以降低血中的三酸甘油酯。 先利用藥物處理有轉染人類脂蛋白解脂酶啟動子序列之質體的人類293細胞，從這些細胞溶解物中發現啟動子下游的報導基因（β-galactosidase）之活性有明顯增加（P＜0.05），證實這些藥物確實可以作用在人類脂蛋白解脂酶啟動子上，促進下游基因的表現。之後同樣的再使用這些藥物處理PLPLWT質體，從實驗結果發現蛋白解脂酶的mRNA確實是存在細胞中，但卻無法偵測到脂蛋白解脂酶活性及濃度的變化，其原因可能是缺少人類脂蛋白解脂酶序列+80 ~ +144的片段，而影響脂蛋白解脂酶蛋白的生成。目前仍無法直接證明變異型脂蛋白解脂酶會受到藥物影響而提高LPL活性。未來若能重新建構一個包含完整脂蛋白解脂酶序列(-1715 ~ +1643)的質體即能對藥物的功能做更進一步探討。 | zh_TW |
| dc.description.abstract | Lipoprotein lipase ( LPL ) plays an important role in the metabolism of plasma lipid metabolism. It catalyzes the hydrolysis of triglycerides from chylomicrons and very low density lipoprotein into glycerol, diacylglycerol and free fatty acids and the free fatty acids are supplied to tissues as sources of metabolic energy or stored as triglycerides after re-esterification. The defect in LPL gene can cause type I hyperlipoproteinemia and affect lipid homeostasis.
In our previous study, the substitution of leucine for valine or arginine at amino acid residue 252 of LPL was found in hyperlipoproteinemic Taiwanese. Both mutated sites at LPL caused hyperlipoproteinemia. We constructed plasmids carrying either LPL promoter and wild type cDNA ( PLPLWT ) or mutated type cDNA ( PLPL252R, PLPL252V ) and transfected these plasmids into HEK293 cells. The aim of this study was to investigate whether drugs（bezafibrate, ciprofibrate, fenofibrate, gemfibrozil）or chemicals （curcumin, esculetin）could increase LPL activity and concentration in transfected cells. We observed significant expression of reporter gene（β-galactosidase） （P＜0.05） in drugs-treated cells transfected with plasmid carrying human LPL promoter. Although mRNA of LPL was expressed in drugs-treated cells transfected with PLPLWT plasmid, the LPL activity and mass in culture medium were not detected. The reason may be the lack of +80 ~ +144 sequence. According to this result, we could not suggest that drugs increase LPL expression. In the future, we should construct new plasmid containing -1715 ~ +1643 sequence. It is helpful for advanced study about effects of drugs. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T01:15:48Z (GMT). No. of bitstreams: 1 ntu-96-R94424012-1.pdf: 797955 bytes, checksum: 11191a62179f79a2e5a39f0edb8562d8 (MD5) Previous issue date: 2007 | en |
| dc.description.tableofcontents | 總目次
總目次.…………………………………………………………………..…….Ⅰ 圖目次……………………………………………………………………..…..Ⅲ 表目次……………………………………………………………….……..….Ⅳ 附錄目次…………………………………………………………….……..….Ⅳ 簡稱或縮寫對照表…………………………………………………………....Ⅴ 中文摘要………………………………………………………………………Ⅷ Abstract……………………………………………………………………..…Ⅸ 第一章 導論 第一節 前言………………………………………………………..…1 第二節 高三酸甘油酯血症………………………………………..…1 第三節 脂蛋白解脂酶的發現……………………………………..…2 第四節 脂蛋白解脂酶的基因構造………………………………..…2 第五節 脂蛋白解脂酶的基本特性…..……………………………....3 第六節 脂蛋白解脂酶的分泌機轉…………………………………..4 第七節 細胞內的訊息傳遞…………………………………………..5 第八節 脂蛋白解脂酶的基因缺陷…………………………………..6 第九節 脂蛋白解脂酶缺乏的臨床症狀……………………………..6 第十節 高脂血症的治療……………………………………………..7 第十一節 藥物特性……………………………………………………..7 第十二節 研究動機……………………………………………………10 第二章 實驗材料與方法 第一節 儀器設備……………………………………………………11 第二節 試藥、試劑組與耗材………………………………………..12 第三節 實驗方法……………………………………………………16 第三章 實驗結果 第一節 質體之序列確認…………………………………..………..23 第二節 溶液對細胞毒性的測試……………………………..……..25 第三節 藥物對細胞毒性的測試……………………………..……..26 第四節 藥物對脂蛋白解脂酶啟動子的影響………………..……..28 第五節 極低密度脂蛋白的分離……………………………………30 第六節 藥物對野生型脂蛋白解脂酶活性的影響…………………30 第七節 pBlue-TOPO-PLPLWT質體之cDNA的確認………………31 第八節 藥物對野生型脂蛋白解脂酶濃度的影響…………………31 第四章 討論………………………………………………………………..33 附圖……………………………………………………………………………38 附表……………………………………………………………………………55 附錄……………………………………………………………………………59 參考文獻………………………………………………………………………79 圖目次 圖1：pBlue-TOPO-(LPL)P質體的初步篩選............................................................38 圖2：pCR3-Uni, pCR3-L252L質體的初步篩選……………………….…....….…39 圖3：pBlue-TOPO-PLPLWT質體的製備-Double digestion………….…………….40 圖4：pBlue-TOPO-PLPLWT質體的初步篩選..…………………………………….41 圖5：pBlue-TOPO-PLPLWT質體的序列……..…………………………………….42 圖6：溶液對細胞存活度的影響…………………..……………………………….43 圖7：藥物對細胞存活度的影響…………………………………………………...44 圖8：以Bezafibrate作用後在細胞溶解物中β-galactosidase活性的比較……...46 圖9：以Ciprofibrate作用後在細胞溶解物中β-galactosidase活性的比較…......47 圖10：以Fenofibrate作用後在細胞溶解物中β-galactosidase活性的比較……...48 圖11：以Gemfibrozil作用後在細胞溶解物中β-galactosidase活性的比較.….....49 圖12：以Curcumin作用後在細胞溶解物中β-galactosidase活性的比較….........50 圖13：以Esculetin作用後在細胞溶解物中β-galactosidase活性的比較……......51 圖14：以藥物作用後在細胞培養液中的脂蛋白解脂酶活性的比較.…………......52 圖15：轉染pBlue-TOPO-PLPLWT質體的人類293細胞之RT-PCR分析圖.….....53 圖16：以藥物作用後在細胞培養液中的脂蛋白解脂酶濃度的比較.…………......54 表目次 表一：實驗過程中所需之寡核酸引子序列………………….….…………..55 表二：世界衛生組織對高脂血症的分類………………………….......…….55 表三：人類脂蛋白解脂酶的組成…………………………………...……….56 表四：人類脂蛋白解脂酶之功能與結構………..…………..………………58 附錄目次 附錄一：pBlue-TOPO質體之限制酶圖譜……….….....………………........59 附錄二：pCR3-Uni質體之限制酶圖譜….……………….……...…….….....60 附錄三：實驗流程…………………….….……….……...…………….….....61 | |
| dc.language.iso | zh-TW | |
| dc.subject | 脂蛋白解脂酶 | zh_TW |
| dc.subject | 活性 | zh_TW |
| dc.subject | 藥物 | zh_TW |
| dc.subject | 核受體 | zh_TW |
| dc.subject | 高三酸甘油酯血症 | zh_TW |
| dc.subject | nuclear receptor | en |
| dc.subject | hypertriglyceridemia | en |
| dc.subject | drug | en |
| dc.subject | activity | en |
| dc.subject | lipoprotein lipase | en |
| dc.title | 藥物對變異型脂蛋白解脂酶活性之影響 | zh_TW |
| dc.title | The Effects of Drugs on The Mutated Lipoprotein Lipase Activity | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 95-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林淑萍,林淑華,江福田 | |
| dc.subject.keyword | 脂蛋白解脂酶,高三酸甘油酯血症,核受體,藥物,活性, | zh_TW |
| dc.subject.keyword | lipoprotein lipase,hypertriglyceridemia,nuclear receptor,drug,activity, | en |
| dc.relation.page | 86 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2007-07-20 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 醫學檢驗暨生物技術學研究所 | zh_TW |
| Appears in Collections: | 醫學檢驗暨生物技術學系 | |
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| File | Size | Format | |
|---|---|---|---|
| ntu-96-1.pdf Restricted Access | 779.25 kB | Adobe PDF |
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