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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 Effects of troglitazone and rosiglitazone on placental OCTN2 expression and function |
Authors: | Huang-Shao Chan 詹皇劭 |
Advisor: | 林君榮 |
Keyword: | 胎盤,肉鹼,OCTN2,troglitazone,rosiglitazone,PPAR, placenta,carnitine,OCTN2,troglitazone,rosiglitazone,PPAR, |
Publication Year : | 2009 |
Degree: | 碩士 |
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 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 |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/25899 |
Fulltext Rights: | 未授權 |
Appears in Collections: | 藥學系 |
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