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为寻找治疗老年性痴呆 (AD)的有效药物 ,运用透射电镜和硫磺素 T荧光分析 ,通过体外孵育方式研究天然抗氧化剂 TA990 1对 β-淀粉样蛋白 (Aβ) 1～ 4 0 的聚集及纤维化的影响。电镜观察显示 ,Aβ1～ 4 0 在 PBS(p H7.4)中室温孵育 7d,其纤维呈晶状聚集 ,直径约 8～ 1 0 nm。TA990 1的存在使 Aβ聚集减少 ,无明显 Aβ纤维形成 ,主要表现为无定形结构。Aβ1～ 4 0 与维生素 E(VE)共同孵育 ,Aβ纤维聚集密度明显下降。 TA990 1和 VE联用使 Aβ纤维的形态主要表现为网状分布的 Aβ原纤维 ,直径约 3～ 5nm。荧光分析揭示 ,TA990 1 ,VE和二者联用对 Aβ纤维形成的抑制率分别为 95.0 % ,3 8.6 %和 6 7.6 %。结果表明 ,TA990 1 ,VE和二者联用均可以不同程度地抑制 Aβ聚集及纤维形成 ,以 TA990 1的抑制作用最强。提示 TA990 1有望发展成为以Aβ为靶治疗 AD的候选药物。
In order to search for an effective drug for the treatment of senile dementia (AD), we studied the aggregation and fibrinolytic activity of TA-990 1 on the level of β-amyloid (Aβ) 1 ~ 40 in vitro by means of transmission electron microscopy and thioflavin T fluorescence analysis The impact of change. Electron microscopy showed that Aβ1 ~ 40 was incubated in PBS (p H7.4) for 7 days at room temperature. The fibers were aggregated in crystal form and the diameter was about 8 ~ 10 nm. The presence of TA990 1 reduced Aβ aggregation, no significant Aβ fiber formation, mainly manifested as amorphous structure. Aβ1 ~ 40 incubated with vitamin E (VE), Aβ fiber aggregation density decreased significantly. The combination of TA990 1 and VE led to the appearance of Aβ fiber mainly in the form of reticular distribution of Aβ fibrils with a diameter of about 3 ~ 5 nm. Fluorescence analysis revealed that the inhibitory rates of TA990 1, VE and their combination on Aβ fiber formation were 95.0%, 8.66% and 7.66%, respectively. The results showed that TA990 1, VE and the combination of both could inhibit Aβ aggregation and fibrosis to a certain extent, and the inhibition by TA990 1 was the strongest. Tip TA990 1 is expected to develop into Aβ targets for the treatment of AD drug candidates.