發(fā)布時(shí)間：2018-02-07 11:14

  本文關(guān)鍵詞： 帕金森病 Salsolinol N-methyl-salsolinol 多反應(yīng)監(jiān)測(cè) α-Synuclein轉(zhuǎn)基因小鼠　出處：《分析科學(xué)學(xué)報(bào)》2017年06期 　論文類型：期刊論文

【摘要】：建立內(nèi)源性兒茶酚異喹啉類物質(zhì)1-甲基-6,7-二羥基-1,2,3,4-四氫異喹啉(Salsolinol,Sal)、6,7-二羥基-1,2-二甲基-1,2,3,4-四氫異喹啉(N-methyl-Sal,NMSal)的高效液相色譜-串聯(lián)質(zhì)譜(HPLC-MS/MS)定量檢測(cè)方法,研究α-Synuclein過表達(dá)對(duì)Sal、NMSal腦內(nèi)水平的影響。實(shí)驗(yàn)優(yōu)化了色譜及質(zhì)譜條件,建立基于多反應(yīng)監(jiān)測(cè)(MRM)技術(shù)的Sal和NMSal的高靈敏度、高選擇性、高重復(fù)性分析方法,并應(yīng)用此方法對(duì)過表達(dá)人源野生型(WT)、突變型(A53T)α-Synuclein蛋白的轉(zhuǎn)基因小鼠腦中Sal、NMSal含量進(jìn)行測(cè)定,發(fā)現(xiàn)WT、A53T轉(zhuǎn)基因小鼠腦內(nèi)Sal、NMSal的含量與對(duì)照組相比均顯著升高。結(jié)果表明:Sal、NMSal分別在6.10pmol/L~6.25nmol/L和97.70pmol/L~100.00nmol/L范圍呈線性(相關(guān)系數(shù)r≥0.9995),日內(nèi)、日間相對(duì)標(biāo)準(zhǔn)偏差(RSD)均小于15.0%,回收率分別為86.5%~90.7%和81.0%~91.4%,Sal、NMSal的檢出限分別為1.53pmol/L和24.4pmol/L,定量限分別為6.10pmol/L和97.7pmol/L。α-Synuclein過表達(dá)會(huì)導(dǎo)致內(nèi)源性神經(jīng)毒素Sal、NMSal水平的升高,可能與帕金森病發(fā)病機(jī)制有關(guān)。
[Abstract]:A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS) method for the quantitative determination of the endogenous catechol isoquinoline (1-methyl-6-dihydroxy-7-dihydroxyquinoline) Salsolinoline Salsolinoline Salsolinoline-6-dihydroxy-2-dimethyl-1-dimethyl-1-dimethyl-4-tetrahydroisoquinoline (N-methyl-SalNMSaline) was developed, and a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MSMS) method was developed for the determination of 1-methyl-6-dihydroquinoline (1-methyl-6-dihydroquinoline) and 4-dihydro-isoquinoline (1-methyl-6-dihydroquinoline). To study the effect of 偽 -Synuclein overexpression on the brain level of Salvia NMSal, the conditions of chromatography and mass spectrometry were optimized, and a high sensitivity, high selectivity and high reproducibility analysis method of Sal and NMSal based on multi-reaction monitoring technique was established. The content of Saline NMSal in the brain of transgenic mice with overexpression of human wild type WTA, mutant A53T) 偽 -Synuclein protein was determined by this method. It was found that the content of Saline NMSal in brain of WTA53T transgenic mice was significantly higher than that of control group. The results showed that the linear range of brain Saline NMSal was 6.10pmol / L 6.25nmol / L and 97.70pmol / L 100.00nmol / L (r 鈮，

本文編號(hào)：1494243