抗氧化剂TA9901对注入大鼠脑皮质内的β-淀粉样蛋白_(1-40)纤维形成的干预作用  

Effect of antioxidants TA9901 on the fibril formation of Aβ_(1-40) injected into cerebral cortex of rat brain

作　　者：庾照学[1] 汪华侨[1] 姚志彬[1] 李光武[1] 

机构地区：[1]中山医科大学解剖学教研室脑研究室,广东广州510080

出　　处：《中国病理生理杂志》2001年第12期1220-1223,共4页Chinese Journal of Pathophysiology

基　　金：广东省科技重点攻关项目资助 (No .2KM0 4 12S);中山医科大学"2 11"工程 ( 980 17)基金资助

摘　　要：目的 :观察抗氧化剂TA990 1对注入脑内的 β -淀粉样蛋白1-40 (Aβ1-40 )纤维形成的干预作用 ,以进一步研究其治疗老年性痴呆 (AD)的作用机制。方法 :12只雄性Wistar大鼠随机分为对照组、TA990 1组、维生素E(VE)组和磷酸缓冲液 (PBS)组。前 3组动物均注射Aβ1-40 ( 2g/L) 5 μL ,PBS组注射相同剂量的 5 0mmol/LPBS。TA990 1组和VE组分别给予TA990 1( 10 0mg·kg-1·d-1)和VE( 10 0mg·kg-1·d-1)腹腔注射 ,对照组和PBS组腹腔注射等体积的生理盐水 ,连续 7d。取注射部位组织作超薄切片 ( 60nm) ,CM 10透射电镜定性观察Aβ纤维的形态 ;另一部分组织作冰冻切片 ,采用甲醇刚果红法染色 ,偏振光显微镜观察Aβ纤维结构。结果 :在Aβ注射部位 ,出现高电子密度沉积物 ,其周围出现许多胶质细胞 ,其胞浆中含有类似于沉积物电子密度的吞噬颗粒 ,而PBS组鼠脑中不存在此现象 ;对照组与VE组的沉积物中 ,出现大量密集的纤维结构 ,纤维直径约 10nm ,类似于在AD脑的老年斑 (SP)中所含的Aβ纤维 ,而在TA990 1组中 ,这种纤维结构非常少见 ,且其数目和密度要远远低于对照组和VE组。偏振光显微镜观察 ,在TA990 1处理组注射部位的偏振光相对较弱。结论 :TA990 1有明显干预Aβ纤维形成和沉积的作用 ,初步提示TA990 1有望发展成?AIM: To clarify if TA9901, a natural antioxidants, could inhibit the formation of β-amyloid(Aβ) fibril when Aβ 1-40 were injected into cerebral cortex of rat brain, and explore the mechanism of action of TA9901 on Alzheimer disesse. METHODS: Twelve Wistar rats (250-300 g) were randomly divided into four groups ( n=3 ). (1) control group; (2) TA9901 treatment group (ip. 100 mg·kg -1 ·d -1 ); (3) Vitamin E(VE) treatment group (ip. 100 mg·kg -1 ·d -1 ); (4) PBS group. 5 μL 0.2% Aβ 1-40 was immediately injected into the right side of the deep cerebral cortex of control, TA9901 and VE group rats. The animals were sacrificed at the seventh day after the injection. The sections of the rat brain that contained the injected field were examined with transmission electron microscopy and Congo red staining with polarized microscopy. RESULTS: Many depositions of high electron density were observed by electron microscopy in the field where Aβ 1-40 was injected. They are intimately intermingled with macrophages and astrocytes. In the field, about 10nm fibrillar structures were observed that appeared similar to the fibrils seen in senile plaque (SP) of the brain of Alzheimer disease (AD). The fields in control and VE group contained richer Aβ fibrils than that in TA9901 group. After the sections stained with Congo red, Aβ 1-40 aggregation demonstrated intense birefringence under, indication the formation of amyloid fibrils. In TA9901 group, there was a weak birefringence.CONCLUSIONS: TA9901 can inhibit the fibril formation of Aβ that was injected into deep cerebral cortex of rat brain, this indicates primarily that TA9901 may be a potential therapeutic drug to interfere with the progression of amyloidgenesis in AD.

关 键 词：淀粉样Β蛋白 阿尔茨海默病 显微镜检查 抗氧化剂 Β-淀粉样蛋白 动物实验 

分 类 号：R338.2[医药卫生—人体生理学] R749.16[医药卫生—基础医学]