TA9902对加速老化小鼠(SAM-P/8)脑Aβ样颗粒沉积的影响  

Effect of TA9902 on the Deposition of Amyloid-β-Like Granules in Senescence-accelerated Mouse (SAM-P/8) Brain

作　　者：汪华侨[1] 谢瑶[1] 袁群芳[1] 李光武[1] 姚志彬[1] 

机构地区：[1]中山大学中山医学院解剖学教研室脑研究室,广东广州510080

出　　处：《中山大学学报（医学科学版）》2003年第3期206-210,i003,共6页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广东省自然科学基金(010698);广东省科技重点攻关基金(2KMO4106S);广东省高校自然科学基金(200058);广州市科技攻关重点基金(2002Z2-E0112)

摘　　要：【目的】观察抗氧化剂TA9901配伍EGb761(简称TA9902)对加速老化鼠P/8(SAM-P/8)脑中Aβ样颗粒沉积的影响,为其临床治疗阿尔采默病(AD)提供科学依据。【方法】选用3月龄雄性SAM-P/8小鼠83只,采用随机数表将其分为TA9001组(15只)、TA9902低剂量组(TA9902-L组,15只)、TA9902高剂量组(TA9902-H组,15只)、EGb761组(10只)、HAT组(Hup-A,10只)和老年组(18只);3月龄雄性SAM-P/8 小鼠15只,作为年轻组。TA9901组和EGb761组饮水中分别加入体积分数5g/L TA9901和0.8g/L EGb761,TA9902-L和TA9902-H组分别加入6g/L和10g/L的TA9002。HAT组石杉碱甲片用量为每只每日0.0125mg。动物喂养期为6.0～6.5个月。用Gomori六胺银法显示海马淀粉样颗粒,并对CA1区的银染颗粒(MSSGs)进行图像分析。【结果】SAM-P/8小鼠脑内MSSG常成群分布(颗粒群长径约40～250μm),以海马的CA3区和齿状回多见。TA9901、EGb761和TA9902能显著减少MSSG平均截面直径、截面面积、平均灰度和MSSG簇数(P<0.05或P<0.01)。高剂量TA9902的作用要强于TA9901、EGb761和低剂量TA9902组(P<0.05)。而且TA9901和EGb761 MSSG的V_V显著减小,TA9901还能减小MSSG的N_V(P<0.05),但对δ无明显影响(P>0.05)。而TA9902-L和TA9902-H均可使MSSG的V_V、N_V有意义地减小,而增加δ?[Objective] To observe the effect of antioxidants TA9901 matched EGb761 (TA9902) on the deposition of amyloid granules in senescence-accelerated mouse (SAM-P/8) and provide scientific basis for TA9902's clinical use. [Methods]Eighty-three male SAM-P/8 (3 months) were randomly divided into six groups. (1) TA9901 group( re = 15) ,5 g/L TA9901 in drinking water. (2) EGb761 group( re = 10), 0. 8 g/L EGb761 in drinking water. (3) Low dose TA9902 (TA9902-L) group ( n = 15) ,6 g/L TA9902 in drinking water. (4) High dose TA9902 (TA9902-H) group ( n, = 15), 10 g/L TA9902 in drinking water. (5) HAT (Hup-A) group( n - 10) ,0. 0125 mg Heu-A in drinking water. (6) Old age group ( n =18) and young age group(3 months,n =18) .normal drinking water and diet. The animals were fed for 6. 0 to 6. 5 months with normal diet. The sections (40μm) of the mice brains were stained by Gomori s methenamine sliver nitrate (Grocott s modification) methods according to standard techniques. Quantitative stereology of the methenamine sliver staining granules (MSSG) in the hippocampus were analyzed by photographs auto-analyzing system. It included the diameter, area, density (gray scale) and clusters number of MSSG. The volume density( Vv) numerical density( Nv) and δ of MSSGs were calculated. [Results] The diameter of clusters of MSSG was about 40 - 250μm. The treatment of TA9901 ,EGb761 and TA9902 produced a significant decrease in the number of clusters, average diameter,area and density of granules( P < 0. 05 or P < 0. 01). The Vv and Nv in TA9902 were significantly smaller than that in old age group. Treatment with TA9902-H had better result than that with TA9901 ,EGb761 and TA9902-L ( P < 0. 05). There was a quantity-effect relationship between TA9902-H and TA9902-L group. Small area granules were markedly increased in TA9901, EGb761 and TA9902 group. [Conclusion] The results suggest that the TA9902 can diminish the deposition of MSSG in the hippocampus of SAM-P/8 brain.

关 键 词：抗氧化剂 银杏 淀粉样蛋白 阿尔采默病 脑组织 动物实验 自由基 

分 类 号：R965[医药卫生—药理学] R749.16[医药卫生—药学]