檳榔素對小鼠著床旁期胚胎之影響--體外及體內實驗之研究

EFFECTS OF ARECOLINE TO THE PERI-IMPLANTATION MOUSE EMBRYOS - IN VITRO and IN VIVO STUDIES

楊高奇(Gau-Chyi Young)

指導教授 ： 劉紹東

高雄醫學大學/醫學院/醫學研究所/碩士(2005年)

摘要

檳榔嚼食在東南亞國家及印度非常盛行，據估計全球約有2億以上的人口是檳榔嚼食者。台灣地區嚼食檳榔的人數正逐漸增多且有年輕化，職業雜異化和都市化的趨勢。在台灣總人口中，約有10%目前或曾經是嚼食檳榔的紅唇族。國際癌症研究組織(IARC)認定嚼食檳榔及同時又抽煙者，確定會導致口腔、咽、喉及食道癌。檳榔對台灣人民健康的危害無法估計。
檳榔子成份中的檳榔素(arecoline)可能是檳榔致癌最重要的因素之一。先前的動物模式實驗也證實檳榔素的致癌性與基因毒性。而動物實驗結果發現，檳榔造成的病變，不是祇有消化道，亦包括其他不必與檳榔直接接觸之器官，如：肝，肺，及泌尿生殖器官。
有關檳榔對懷孕影響的研究很少。就目前所知，嚼食檳榔的懷孕婦女所產之胎兒，在體重上會較輕。而目前在檳榔對於懷孕之影響均偏重於生產後之調查，但不可掉以輕心的是，檳榔內含物對胚胎早期發育的影響如果到達一定程度，可能會影響著床而導致早期流產，以致於被學者忽略。
為了完整瞭解檳榔素對胚胎發育過程之影響，本實驗室乃針對著床時期老鼠胚胎，將檳榔素對著床過程的影響作分析。在體內實驗中，將胚胎著床旁期的母鼠餵以不同劑量的檳榔素，並觀察胚胎著床情形。在體外實驗中，將著床前胚胎培養在含有不同濃度檳榔素的培養液中，經過不同培養時間後，就胚胎的型態、面積及發育狀況加以觀察及計算，以探究檳榔素對著床時期胚胎在型態學上的影響。
實驗結果發現，在in vivo的環境下，越高劑量的檳榔素，會使著床時期的胚胎著床率降低。不論濃度高低之檳榔素在in vitro 的環境下，對於著床時期之小鼠胚胎之生長均存在抑制之作用。尤其是在培養72小時後，培養於高於8.47x10-4M之檳榔素之胚胎之生長範圍顯著小於對照組胚胎。
因此由本實驗之結果推論，檳榔素對於正在進行著床的胚胎生長有抑制的作用，且影響著床反應之進行。

關鍵字

檳榔 ； 抑制outgrowth ； 著床 ； 小鼠胚胎 ； 檳榔素

並列摘要

It was estimated that there were at least 200 million people worldwide and about 10% people in Taiwan practiced the habit of chewing the betel quid. Arecoline is one of the major ingredients in betel nut and it has been related to the malignancy on digestive, respiratory, reproductive system and to adverse birth outcomes. However, as a critical stage of gestation, it is important to establish the knowledge about the effect of arecoline to the embryos during the processes of implantation. In the present study, we fed pregnant mice with different dosage of arecoline to see whether embryos could implant in uterus. When pregnant mice were fed with 200?慊 arecoline once a day for three days, the implantation rate was decreased dramatically. In vitro studies, we used the model of blastocyst outgrowth to evaluate the growth of mouse peri-implantation embryos under various concentrations of arecoline for various times of incubation. We found that the growth area of mouse embryos in arecoline-containing groups were smaller than control embryos. In addition, growth area of embryos with 8.47x10-4M of arecoline was smaller than control significantly. Therefore, we suggested that arecoline, the major content of betel nut, inhibits the growth implanting mouse embryos in vitro and exerts poisonous effects on implanting embryos during the process of implantation in vivo.

並列關鍵字

betel nut ； arecoline ； mouse embryo ； implantation ； inhibit outgtowth

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