- 學位論文
人蔘皂苷Rb1誘導小鼠胚胎產生粒線體依賴性凋亡
Ginsenoside Rb1 Induces Mitochondrial-Dependent Apoptosis in Mouse Blastocysts
摘要
Ginsenoside Rb1 是一種從人參根部萃取具有藥理性的化合物且已被證實具有抗癌、抗氧化與抗發炎的功效。本研究利用 ginsenoside Rb1 對小鼠囊胚期胚胎進行體外發育的研究，來探討 ginsenoside Rb1 對於著床前小鼠胚胎發育的影響。小鼠囊胚期胚胎分別與 50 μg/ml 或 100 μg/ml 的 ginsenoside Rb1共培養後，發現ginsenosideRb1會導致囊胚期胚胎細胞數目顯著減少，同時引起細胞凋亡的現象，而細胞數目減少主要以內細胞團為主，但滋養層細胞數目也發現有明顯的下降。接著探討 ginsenoside Rb1 引起囊胚細胞凋亡的機轉，發現是因為增加氧化壓力而誘發粒腺體依賴的凋亡機轉，而以抗氧化劑 Nacetylcysteine 則可有效阻斷 ginsenosideRb1 所導致的粒線體膜電位的喪失、半胱氨酸蛋白酶 (caspases) 的活化以及小鼠囊胚的細胞凋亡。這些結果證實 ginsenoside Rb1 會透過引起小鼠囊胚細胞的凋亡，而對胚胎發育造成傷害.
並列摘要
Ginsenoside Rb1 is one of pharmacologically active compounds that composes mainly root of ginseng. Ginsenoside Rb1 has been reported to promote anti-cancer, anti-oxidant, and anti-inflammation. In this study, we examined the teratogenic effect of ginsenoside Rb1 during mouse embryonic development in vitro. Mouse blastocysts treated with 50 or 100 μg/ml ginsenoside Rb1 showed dose-dependently reduced the total cell numbers and increased blastocyst apoptosis. ICM was more sensitive to ginsenoside Rb1 treatment at 50 μg/ml dose. Meanwhile 100 μg/ml ginsenoside Rb1 reduced not only ICM but also lowered trophectoderm cell significantly compared to untreated control group. Furthermore, ginsenoside Rb1-induced blastocyst apoptosis was ROS dependent-mitochondrial apoptotic pathway as shown by NAC co-treatment could block loss of mitochondrial membrane potential and subsequently reduced caspases-dependent apoptosis in mouse blastocysts. Active caspase-9 and 3 were involved in mediating blastocyst apoptosis induced by ginsenoside Rb1. Bax was upregulated by ginsenoside Rb1 treatment and this protein might be important in blastocyst apoptosis. These findings show for the first time that ginsenoside Rb1 exhibits teratogenic effects on mouse blastocysts by apoptosis induction.