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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林君榮 | |
dc.contributor.author | Huang-Shao Chan | en |
dc.contributor.author | 詹皇劭 | zh_TW |
dc.date.accessioned | 2021-06-08T06:56:48Z | - |
dc.date.copyright | 2009-09-15 | |
dc.date.issued | 2009 | |
dc.date.submitted | 2009-07-22 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/25899 | - |
dc.description.abstract | 胎盤是一個懷孕期間,為了維持胚胎與胎兒發育所暫時產生的器官。藥物與營養物可能透過簡易擴散、便利運輸和主動運輸來穿透胎盤到胎兒身體,因此,懷孕婦女所服用的藥物可能會透過胎盤對於母體本身或是胎兒造成一些有益或是有害的作用。對於患有糖尿病的婦女,在懷孕期間仍然需要服用藥物來降低體內過高的血糖以免對人體有害,有鑑於肉鹼攝取和滋養層母細胞融合對於胎兒的發育有絕對必要的重要性,在我們的研究中,主要對於兩種同類型的第二型糖尿病藥物:troglitazone和rosiglitazone是否能對於胎盤肉鹼運輸和滋養層母細胞融合有所改變進行探討。因為肉鹼主要由第二型新奇有機陽離子轉運蛋白 (OCTN2) 所運送,而滋養層母細胞融合由syncytin來完成,我們藉由給予胎盤絨毛膜癌BeWo細胞株這兩種藥物,來觀察其對OCTN2和syncytin的蛋白質表現與功能的影響。
由西方點墨法的結果可知在給予troglitazone 72小時後,在細胞膜蛋白的部分,OCTN2的蛋白質表現下降,在刷狀絨毛膜也能觀察到類似的結果。由OCTN2動力學的實驗結果得知carnitine uptake的Vm 值也是減少的情形。而syncytin的蛋白是大量地增加。相反的,在rosiglitazone的處理下,OCTN2的蛋白質表現及carnitine uptake則沒有明顯改變。而syncytin蛋白僅有少許的變多。這些結果可能顯示懷孕婦女若是服用troglitazone,雖然可以有利於胎盤的發育,卻會減少肉鹼穿透胎盤的量,進而影響胎兒對肉鹼的攝取。我們接著分析可能調控OCTN2蛋白表現的轉錄因子,PPAR α與RXR α的蛋白表現量,結果發現RXR α 的表現量下降了,PPAR α的表現量則不變。RXR α蛋白量的改變或許與PPAR | zh_TW |
dc.description.abstract | The placenta is a temporary organ required for the development of the embryo and fetus. Substances can transfer across the placenta through passive diffusion, facilitated diffusion, and active transport. Thus, during pregnancy, drugs and nutrients taken by pregnant women may pass to the fetus via placental transfer and may have pharmacological or toxicological effects on the fetal development. For women with gestational diabetes, it is necessary to take daily medication to control the levels of blood sugar. Our research of interest is to study the effects of the two anti-hyperglycemic agents, troglitazone and rosiglitazone, on placental carnitine transport and syncytialization, given that both are required for fetal development. Since placental carnitine transfer is mainly mediated by the novel organic cation/carnitine transporter 2 (OCTN2), and syncytialization is achieved by syncytin. The function and protein expression of OCTN2, syncytin were investigated in human choriocarcinoma BeWo cell lines under the treatment of these thiazolidinediones.
Western blot analysis shows that troglitazone treatment resulted in a decline of OCTN2 expression on the crude membrane fraction of BeWo cells, reaching a marked decrease in 72 hours. The OCTN2 expression on the brush border membrane portion also demonstrated a similar result to that on the crude membrane. The kinetic study shows that the capacity (i.e., Vm) of carnitine uptake significantly decreased as well. Syncytin expression increased dramatically compared to control. On the contrary, the contributions of rosiglitazone in the regulation and function of OCTN2, syncytin expression were minimal. These data suggest that troglitazone may reduce placental carnitine transfer in pregnant women taking troglitazone as a hyperglycemic agent. The transcriptional factors that regulate OCTN2 expression , PPAR | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T06:56:48Z (GMT). No. of bitstreams: 1 ntu-98-R96423019-1.pdf: 2593485 bytes, checksum: 406befed3638d32a0d36a40b4b6a51f2 (MD5) Previous issue date: 2009 | en |
dc.description.tableofcontents | 中文摘要 i
Abstract ii 第一章 文獻回顧 1 1.1. 胎盤的生理 1 1.1.1. 胎盤結構與發育 1 1.1.2. 胎盤物質運輸 2 1.1.3. 懷孕用藥的未知安全性 3 1.1.4. 胎盤絨毛膜細胞株 (placental choriocarcinoma cell lines) 4 1.1.5. 胎盤的其他屏障 5 1.1.6. 使用細胞株研究物質吸收的限制 5 1.2. 輸送營養物質或藥物的重要轉運蛋白 6 1.2.1. 新奇有機陽離子第二型轉運蛋白 (Novel organic cationic transporter type 2, OCTN2) 6 1.2.2. 葡萄糖轉運蛋白 (Glucose transporter) 9 1.3. 第二型糖尿病藥物 11 1.3.1. Thiazolidinediones (TZD) 11 1.3.2. TZD的副作用考量 12 1.3.3. Peroxisome proliferator activated receptors (PPARs) 14 1.3.4. PPAR response element (PPRE) 17 第二章 實驗目的 18 第三章 實驗材料 19 3.1. BeWo細胞培養 19 3.2. 蛋白質濃度分析 20 3.3. BeWo細胞的肉鹼攝取量研究 20 3.4. BeWo細胞的葡萄糖攝取量研究 20 3.5. 細胞膜 (Crude membrane)、刷狀絨毛膜 (Brush border membrane, BBM) 和核蛋白(nuclear extract) 的萃取 21 3.6. 西方墨點法 (western blot) 23 3.7. H2O2測定所用試劑 25 3.8. 其它儀器 26 第四章 實驗方法 27 4.1. BeWo細胞株培養 27 4.2. 藥物處理 27 4.3. 膜蛋白萃取 (Crude membrane extraction) 27 4.4. 刷狀膜萃取 (Brush Border Membrane extraction) 28 4.5. 鹼性磷酸酶 (Alkaline phosphatase, ALP) 測定 28 4.6. 核蛋白萃取 (nuclear extraction) 29 4.7. 蛋白質濃度測定 30 4.8. 西方點墨法 (Western blot) 30 4.9. 肉鹼、葡萄糖的攝取動力學 (uptake kinetics) 研究 31 4.10.H2O2的測定 33 4.11. 找尋OCTN2上游可能的PPAR binding sequence 33 4.12.統計檢定 33 第五章 實驗結果 35 5.1. 第二型糖尿病藥物對BeWo 細胞分化的特殊融合蛋白質syncytin影響 35 5.2. 刷狀外緣絨毛膜 (Brush Border Membrane, BBM) 萃取 35 5.3. 第二型糖尿病藥物對BeWo 細胞OCTN2在細胞膜和刷狀外緣絨毛膜的量之變化 36 5.4. BeWo細胞經由第二型糖尿病藥物處理後的肉鹼攝取動力學 36 5.5. 第二型糖尿病藥物對BeWo 細胞PDZK1在細胞膜和刷狀外緣絨毛膜的量 之變化 36 5.6. 第二型糖尿病藥物對BeWo 細胞PPAR 在細胞核内和細胞質的量之變化 37 5.7. 第二型糖尿病藥物對BeWo細胞RXR 在細胞核内和細胞質的量之變化 37 5.8. 第二型糖尿病藥物對BeWo 細胞GLUT1在細胞膜和刷狀外緣絨毛膜的量 之變化 38 5.9. BeWo細胞經由第二型糖尿病藥物處理後的去氧葡萄糖攝取動力學 38 5.10. 細胞內活性氧化物 (Reactive oxygen species, ROS) H2O2經第二型糖尿病 藥物藥物處理後的改變 38 第六章 結果討論 51 6.1. 本研究發現的thiazolidinedione可能造成的生理影響 51 6.1.1. 代謝路徑 51 6.1.2. 胎兒發育 51 6.2. 可能分子機轉 52 6.2.1 OCTN2與RXR蛋白下降的原因 52 6.2.2 Thiazolidinedione對於滋養層細胞的分化影響 53 6.2.3 Troglitazone與氧化逆境 (oxidative stress) 的關係 54 6.2.4 Thiazolidinedione的作用中,與PPAR無關的功能 55 6.3. 臨床上服用troglitazone或rosiglitazone的追蹤 55 第七章 結論 58 參考文獻 (References) 59 附錄 一 71 附錄 二 80 | |
dc.language.iso | zh-TW | |
dc.title | 比較同類型糖尿病藥物troglitazone和rosiglitazone如何影響胎盤新型有機陽離子轉運蛋白第二型 (OCTN2) 的表現與功能 | zh_TW |
dc.title | Effects of troglitazone and rosiglitazone on placental OCTN2 expression and function | en |
dc.type | Thesis | |
dc.date.schoolyear | 97-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳美如,孔繁璐,楊家榮 | |
dc.subject.keyword | 胎盤,肉鹼,OCTN2,troglitazone,rosiglitazone,PPAR, | zh_TW |
dc.subject.keyword | placenta,carnitine,OCTN2,troglitazone,rosiglitazone,PPAR, | en |
dc.relation.page | 85 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2009-07-22 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 藥學研究所 | zh_TW |
顯示於系所單位: | 藥學系 |
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