| 摘要: | 許多研究指出，氧化壓力與內質網壓力會參與一些人類的神經性疾病，例如亨丁頓舞蹈症（Huntington's disease）、帕金森氏症（Parkinson's disease）、prion蛋白相關疾病等。過氧化增殖受體γ (peroxisome proliferator-activated receptorγ, PPARγ)可作為治療神經性退化疾病的標的，因為激活PPARγ可活化神經膠細胞以抗發炎。PPARγ激活劑目前已被研究人員作為許多慢性神經退化疾病前臨床模型的依據，而日漸受到研究人員的重視。本實驗的目的首先探討PPARγP465L/+小鼠（PPARγ突變）和野生型小鼠，利用QPCR檢測其海馬迴和小腦，以了解其抗氧化與內質網壓力基因的相關性；接下來利用H2O2產生氧化壓力誘導N2A細胞死亡的條件下，研究PPARγ激活劑（rosiglitazone, Rosi）對N2A細胞的神經保護作用。關於氧化壓力和內質網壓力，我們利用QPCR檢測PPARγP465L/+小鼠和野生型小鼠的SOD1, BiP, CHOP, Herpud1, CREB的mRNAs表現量。結果顯示，PPARγP465L/+小鼠的SOD1, BiP, CHOP, 和Herpud1的mRNAs表現量在海馬迴和小腦有顯著下降，這表明了PPARγ功能缺失會導致抗氧化能力下降與內質網損傷。將N2A細胞經Rosi 10 μM處理3天和56天、在100 μM H2O2氧化壓力的環境下，結果表明，Rosi處理組，其細胞存活率有顯著增加，顯示PPARγ有神經保護作用。
Many studies suggested that oxidative stress and ER (Endoplasmic Reticulum) stress are involved in some human neuronal diseases, such as Alzheimer’s disease, Parkinson’s disease and prion disease. However, recent studies have pointed out to the role of PPARγ agonist (rosiglitazone, Rosi) has received increasing attention. Researchers have provided a multitude of evidences in preclinical models of a variety of chronic neurodegenerative conditions. The aim of this study is to investigate PPARγ P465L/+ mice and wild-type mice that detected associate of antioxidant stress and ER stress gene expression that in hippocampus and cerebellum. Next, to investigate the neuroprotective effects of PPAR γ, on the oxidative stress induced death in the N2A cells. We monitored the antioxidative and ER stress markers SOD1, Bip, CHOP, and Herpud1 expression by quantitative real-time PCR. We attempted to detect PPARγ P465L/+ mice. Results suggested the loss of PPARγ function could lead to the decreased antioxidant capacity and ER injure. N2A cell treated with 10 μM rosiglitazone in 100 μM H2O2 for the 3 day and 56 days in the oxidative stress, show that rosiglitazone group has significantly increased neuroprotective effects in the N2A. |
