摘要
老年性痴呆脑中β 淀粉样蛋白 (Aβ)聚集和毒性作用与自由基的产生关系密切 ,TA990 1具有极强的抗氧化和清除自由基的作用。本研究重点探讨TA990 1对在Aβ聚集过程中肽自由基形成的影响。用 0 1%Aβ1～ 40 单独或分别与相同百分浓度的TA990 1、维生素E(VE)乳化液和TA990 1加VE在 37℃恒温箱中共同孵育 ,在孵育液中加入 5 0mM的自由基捕捉剂本叔丁基氮酮 (PBN) ,分别在孵育后的第 1d、2d、3d、6d利用BrukerRCS10 6电子顺磁共振仪 (EPR)检测 ,分析自由基的性质和药物对自由基的清除率。结果证实 ,在不同条件下 ,Aβ在老化过程中产生曲线强度和分裂不同的EPR曲线 ;以第 3dEPR谱第二峰的线宽代表各组自由基的强度 ,计算TA990 1、VE和TA990 1加VE对自由基的清除率分别为5 0 4 6 %、31 2 8%和 36 77%。上述结果提示 ,TA990 1抑制Aβ的毒性作用和纤维形成与其强烈的清除自由基的作用有关。
The free radical generation may be involved in the processes of amyloid β protein(Aβ)aggregation and/or neurotoxicity in brain of Alzheimer's disease.TA9901 has strong capability of antioxidation and scavenging free radicals.In this paper,the effect of TA9901 on Aβ peptidyl free radical generation was studied by electron paramagnetic resonance(EPR).The solution of 0.1% Aβ 1～40 in 50 mM PBS(pH 7.4) was incubated alone or together with 0.1% TA9901,0.1% VE and 0.1% TA9901+VE respectively in a 37 ℃ water bath for 6 days,50 mM N tert butyl α phenylnitrone(PBN)a spin trapper,was added into the solutions.The peptide solution was imbibed into quartz capillary tube that was subsequently sealed at both ends.EPR spectra in different time of the incubating period(1 st,2 nd,3 rd and 6 th day)were acquired on a EPR spectrometer.The results show that the EPR spectra and its peak intensity ratio in drug treated groups had gradual changes in the numbers and positions of peaks.If the width of the second peak of the EPR spectrum at the third day represented the free radical intensity of the group at the time,the scavenging rate of TA9901,VE and TA9901+VE were 50.46%,31.28% and 36.77% respectively.The results indicated that the inhibitory mechanism of TA9901 on Aβ aggregation and/or neurotoxicity is associated with inibition of TA9901 on Aβ peptidyl free radical generation.
出处
《天然产物研究与开发》
CAS
CSCD
2002年第3期58-62,共5页
Natural Product Research and Development
基金
广东省科技重点攻关项目 (NO .2KMO410 6S)
广东省高校自然科学基金 (NO .2 0 0 0 5 8)
广东省自然科学基金 (NO .0 10 698)
