本文選題：帕金森病　切入點(diǎn)：黑質(zhì)　出處：《華北理工大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的對(duì)帕金森病(Parkinson’s disease,PD)模型大鼠進(jìn)行側(cè)腦室注射抗氧化劑、氧化應(yīng)激誘導(dǎo)劑,觀察大鼠行為學(xué)變化、檢測(cè)氧化應(yīng)激相關(guān)指標(biāo)的含量變化及自噬相關(guān)蛋白的表達(dá),探討氧化應(yīng)激對(duì)帕金森病模型大鼠黑質(zhì)自噬相關(guān)蛋白表達(dá)的影響,為帕金森病的發(fā)病機(jī)制及治療提供理論依據(jù)。方法144只清潔級(jí)健康雄性SD大鼠隨機(jī)分為假手術(shù)組(sham組)、帕金森病模型組(PD組)、抗氧化劑NAC組(NAC組)和氧化應(yīng)激誘導(dǎo)劑Aβ組(Aβ組),采用頸背部皮下注射魚藤酮制作PD模型,待模型制備成功后,sham組和PD組大鼠進(jìn)行側(cè)腦室注射生理鹽水5μL,NAC組大鼠進(jìn)行側(cè)腦室注射N-乙酰半胱氨酰(N-acetylcysteine,NAC)5μL,Aβ組大鼠進(jìn)行側(cè)腦室注射β淀粉樣蛋白(Beta amyloid protein,Aβ)5μL,分別在實(shí)驗(yàn)后4 d和8 d選取18只大鼠,用微量酶標(biāo)法檢測(cè)大鼠黑質(zhì)GSH、GSH-Px、SOD和MDA的含量的變化;采用免疫組化法和免疫印跡法檢測(cè)大鼠黑質(zhì)自噬相關(guān)蛋白Beclin1、LC3的表達(dá)水平。所得實(shí)驗(yàn)數(shù)據(jù)用Excel建庫(kù)后用SPSS(23.0)軟件包對(duì)所得數(shù)據(jù)進(jìn)行統(tǒng)計(jì)分析,所得數(shù)據(jù)均以均數(shù)±標(biāo)準(zhǔn)差(xˉ±s)表示,多組間比較采用單因素方差分析(one-way ANOVA),以P0.05認(rèn)為有統(tǒng)計(jì)學(xué)意義。結(jié)果1 sham組大鼠懸掛時(shí)間較長(zhǎng),評(píng)分值較高;與sham組相比,PD組大鼠評(píng)分值降低(P0.01),8 d組低于4 d組(P0.05);與PD組相比,NAC組大鼠評(píng)分值升高(P0.01),8 d組高于4 d組(P0.05);與PD組相比,Aβ組大鼠評(píng)分值降低(P0.01),8 d組低于4 d組(P0.05)。2 1)sham組大鼠黑質(zhì)中GSH、GSH-Px、SOD的含量表達(dá)較高;與sham組相比,PD組大鼠黑質(zhì)中GSH、GSH-Px、SOD含量降低(P0.05),8 d組低于4 d組(P0.05);與PD組相比,抗氧化劑NAC組大鼠黑質(zhì)中GSH、GSH-Px、SOD含量增高(P0.05),8 d組高于4 d組(P0.05);與PD組相比,氧化應(yīng)激誘導(dǎo)劑Aβ組大鼠黑質(zhì)中GSH、GSH-Px、SOD含量降低(P0.05),8 d組低于4 d組(P0.05)。2)sham組大鼠黑質(zhì)中MDA的含量表達(dá)較低;與sham組相比,PD組大鼠黑質(zhì)中MDA含量增多(P0.05),8 d組高于4 d組(P0.05);與PD組相比,抗氧化劑NAC組大鼠黑質(zhì)中MDA含量降低(P0.05),8 d組低于4d組(P0.05);與PD組相比,氧化應(yīng)激誘導(dǎo)劑Aβ組大鼠黑質(zhì)中MDA含量增高(P0.05),8 d組高于4 d組(P0.05)。3 sham組大鼠黑質(zhì)中表達(dá)少量Beclin1、LC3陽(yáng)性細(xì)胞;與sham組相比,PD組大鼠黑質(zhì)中Beclin1、LC3蛋白表達(dá)和LC3II/LC3-I比值增多(P0.05),8 d組高于4d組(P0.05);與PD組相比,抗氧化劑NAC組大鼠黑質(zhì)中Beclin1、LC3蛋白表達(dá)和LC3II/LC3-I比值降低(P0.05),8 d組低于4 d組(P0.05);與PD組相比,氧化應(yīng)激誘導(dǎo)劑Aβ組大鼠黑質(zhì)中Beclin1、LC3蛋白表達(dá)和LC3II/LC3-I比值增多(P0.05),8 d組高于4 d組(P0.05)。結(jié)論1氧化應(yīng)激參與了帕金森病的發(fā)病、發(fā)展過(guò)程。2自噬參與了帕金森病的發(fā)病、發(fā)展過(guò)程。抗氧化劑NAC能夠抑制自噬相關(guān)蛋白的表達(dá),氧化應(yīng)激誘導(dǎo)劑Aβ可上調(diào)自噬相關(guān)蛋白的表達(dá)。3氧化應(yīng)激對(duì)帕金森病模型大鼠黑質(zhì)自噬相關(guān)蛋白的表達(dá)具有促進(jìn)作用,抗氧化應(yīng)激可抑制帕金森病模型大鼠黑質(zhì)自噬相關(guān)蛋白的表達(dá),具有神經(jīng)保護(hù)作用。
[Abstract]:The purpose of Parkinson's disease (Parkinson 's disease, PD) in a rat model of intraventricular injection of antioxidants, oxidative stress induced behavioral changes of the rats were observed, the expression of oxidative stress related indexes and the content change of autophagy related proteins, to investigate the impact of oxidative stress on the expression of autophagy related protein in substantia nigra of rats with Parkinson disease model and provide a theoretical basis for the pathogenesis of Parkinson's disease and treatment. Methods 144 clean grade healthy male SD rats were randomly divided into sham operation group (Group sham), Parkinson disease model group (PD group), NAC group (group NAC) antioxidants and oxidative stress inducer group A beta (A beta group), the PD model is established by subcutaneous injection of rotenone, after the model was successfully established, sham group and PD group rats were ICV injection of saline 5 L NAC rats were ICV injection of N- acetyl cysteinyl (N-acetylcysteine, NAC) 5 L, A beta 緇勫ぇ榧犺繘琛屼晶鑴戝娉ㄥ皠尾娣，

本文編號(hào)：1629645