异氟醚和七氟醚促进β淀粉样蛋白1-40寡聚化和纤维形成  

Isoflurane and sevoflurane enhance amyloid-beta protein in oligomerization and fibril formation

作　　者：刘永哲[1] 高明龙[1] 张宏[1] 

机构地区：[1]解放军总医院麻醉手术中心,北京100853

出　　处：《中国药物与临床》2008年第2期85-87,I0001,共4页Chinese Remedies & Clinics

基　　金：国家自然科学基金资助项目(3057192)

摘　　要：目的研究异氟醚和七氟醚对β-淀粉样蛋白1-40(Aβ1-40)的促寡聚化作用和纤维形成。方法对照组:Aβ1-40用磷酸盐缓冲液(PBS)配制。I组:Aβ1-40采用溶解1.3MAC异氟醚的PBS配制。S组:Aβ1-40采用溶解1.3MAC七氟醚的PBS配制。在30min、1d、2d、3d、4d、5d、6d、7d时各组进行荧光分析,在空白组30min和7d、其余各组4和7d时进行透射电镜分析。结果与空白组相比,I组在各时点的荧光强度均明显增强(P<0.05),S组在3、4d以外各时点荧光强度明显增强(P<0.05);与I组比较,S组30min和7d时荧光强度差异无统计学意义(P>0.05),其余时点明显降低(P<0.05)。I组4d比空白组7d形成更加密集的纤维状聚集物,7d可以见到团状聚集。S组老化4d无明显的纤维状结构,但7d时可以见到比空白组7d更加明显的网状纤维。结论异氟醚和七氟醚都可以促进Aβ的寡聚化和纤维形成。Objective To investigate the enhancement of amyloid-beta proteinl-40 （Aβ1-40） in oligomerization and fibril formation by isoflurane and sevoflurane. Methods Control group： Aβ1-40 incubated in PBS. Group I： Aβ1-40 incubated in PBS with 1.3 MAC isoflurane dissolved. Group S： Aβ1-40 incubated in PBS with 1.3 MAC sevoflurane dissolved. The concentration of Aβ1-40 was 0.2mg/ml. The concentration of Aβ1-40 fibril was measured by thioflavine fluorimetric analysis at 30 min, 1, 2, 3, 4, 5, 6 and 7 d in all groups. The structure of Aβ1-40 fibril was observed by transmission electron microscope analysis at 30 min, and 7 d in control group, and 4 d and 7 d in groups I and S. Results Compared with control group, fluorescence intensity in group I was remarkably increased at all time points （P〈0.05）, as were in group S at all time points except 3 d and 4 d （P〈0.05）. Compared with group I, group S showed greatly decreased fluorescence intensity at all time points except for 30 min and 7 d. A higher density of fibrillar Aβ1-40 aggregation was observed at 4 d in group I compared with that at 7 d in control group and a massive aggregation was observed at 7 d in group I. Fibrillar Aβ1-40 aggregation was hardly observed at 4 d in group S but a higher density of fibrillar Aβ1-40 aggregation was observed at 7 d in group S as compared with the same time point in control group. Conclusion Both isoflurane and sevoflurane may enhance amylold-beta protein in oligomerization and fibril formation, whereas such effect was found to be more active with isoflurane than with sevoflurane.

关 键 词：阿尔茨海默病 淀粉样Β蛋白 异氟醚 七氟醚 

分 类 号：R96[医药卫生—药理学]