去除雄性素受體對腦外傷小鼠mTOR表現影響之評估

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題名:	去除雄性素受體對腦外傷小鼠mTOR表現影響之評估 Evaluation of the effect of androgen receptor knockout on the expression of mTOR in mice following TBI
作者:	余錦權 ER, JIN-QUAN
貢獻者:	楊良友
關鍵詞:	雄性素受體;腦創傷 Androgen receptor;Traumatic brain injury;mTOR
日期:	2015-07-13
上傳時間:	2020-08-19 14:27:22 (UTC+8)
摘要:	創傷性腦損傷（Traumatic Brain Injury, TBI）的死亡率與導致身心障礙的病患在全球不斷持續增加中。根據先前的研究發現雄性素受體 (Androgen Receptor) 可調節染色體中組織蛋白及DNA並調控基因表現，具有保護腦神經細胞的作用，減少因腦損傷帶來的傷害，因此在此類傷害之冶療上可能有所益助的。先前的文獻證明在腦外傷病患中因缺乏雄性素受體將會延長其住院時間和降低獨立性神經功能等，本文回顧並檢視缺乏雄性素受體小鼠在腦損傷模式是否下會惡化受傷程度，進而去增加損傷的發生。首先利用細胞實驗得知在 C6 glioma細胞中經L-glutamate刺激2小時內會增加phosphorylation mTOR (p-mTOR) 蛋白表現量，在24小時會減少C6 glioma細胞 p-mTOR 蛋白表現量。進一步探討腦損傷在動物實驗方面對mTOR蛋白表現與雄性素受體的影響得知缺乏雄性素受體小鼠 (ARKO) 與一般小鼠 (WT) 經TBI處理後4小時與24小時後p-mTOR蛋白表現量都減少。同時，在實驗中也發現ARKO組小鼠對比WT小鼠，ARKO組小鼠p-mTOR蛋白表現量相對顯著減少。綜合上述實驗結果，缺乏雄性素受體小鼠在神經系統受傷後mTOR蛋白表現量顯著減少，並顯示缺乏雄性素受體在受傷後可能導致神經細胞更容易受傷害和減緩神經修復。 Traumatic brain injury (TBI) is a continuously increasing cause of mortality and disability around the world. It was found in a previous study that androgen receptors (AR) can change the protein of chromosomes and DNA in regulation of gene expression. It plays a protective role for nerve cells and reduces the damage caused by brain injuries, thus it is beneficial to the injured. It is documented that patients lacking androgen receptors who have traumatic brain injury will have an extended length of hospitalization and show lower functional independence measure scores. My study aims to explore the molecular pathways of mTOR and its path mechanism in androgen receptor knock out (ARKO) mice and wide type (WT) mice with TBI. First, L-glutamate stimulated C6 glioma cells in cell experiments and western blot showed that expression of phosphorylation mTOR (p-mTOR) increased for 2 hours and then reduced 24 hours after L-glutamate is induced. To further investigate the effects of brain injury in animal experiments on mTOR protein expression, western blot showed that the expression of mTOR in both ARKO and WT mice decreased significantly at 4 and 24 hours after TBI treatment. The proteins level of ARKO further decreased significantly compared to WT mice. This article discusses the physiological and pathological roles of mTOR when there is a lack of androgen receptor in the nervous system after brain injury. Due to the dual effects, lack of androgen receptor may lead to nerve cells that are more susceptible to injury have slower nerve repair.
描述:	碩士指導教授:楊良友委員:高永旭委員:陳彥州
資料類型:	thesis
顯示於類別:	[醫學科學研究所] 博碩士論文

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