SVHRP对Aβ_(1-40)处理后大鼠海马突触形态学改变的抑制作用  

SVHRP prevents synaptic morphological changes in hippocampus of Aβ_(1-40)-treated rats

作　　者：于胜波[1] 宫瑾[1] 迟彦艳[1] 彭岩[2] 高船舟[3] 赵杰[2] 张万琴[2] 隋鸿锦[1] 

机构地区：[1]大连医科大学基础医学院解剖学教研室 [2]大连医科大学基础医学院生理学教研室 [3]大连医科大学基础医学院中心实验室,大连116044

出　　处：《神经解剖学杂志》2010年第3期249-254,共6页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(30770737)

摘　　要：目的:探索蝎毒耐热蛋白(SVHRP)对淀粉样β蛋白(Aβ)神经毒性的抑制作用。方法:在大鼠海马内每侧注射Aβ1-40(10μg/2μl)后1d,给予腹腔SVHRP(0.5～2μg/100g),1次/d,连续10次。建模16d后分别进行海马部位的突触体素免疫组织化学分析和突触超微结构计量观察。结果:与对照组比较,Aβ组大鼠突触体素免疫反应强度和电镜下突触密度明显下降(P<0.01),小突触丢失为主,突触终末可见突触小泡大量集聚,突触活性区平均长度增加。SVHRP干预组大鼠实触体素免疫反应强度和电镜下突触密度明显高于Aβ组大鼠(P<0.01),突触终末内未见突触小泡过量集聚,但小突触比例显著增加(P<0.01)。结论:以上结果强有力的提示,Aβ是突触退变的始动因素,SVHRP可抑制Aβ引起的突触退变,有可能成为治疗Alzheimer病(AD)的一种药物。Objective： To investigate the inhibition of scorpion venom heat-resistant protein （SVHRP） on the neurotoxicity of the amyloid beta-protein （Aβ）. Methods： After injected Aβ1-40 （10 μg/2 μl ） into hippocampus of rats one day; then injected SVHRP intraperitoneally once a day （0.5 -2μg/100 g） , for consecutive 10 days. And at 16 days following model establishment, synaptophysin of rat hippocampus was determined by immunohistochemistry. The ultrastructures of the synapses of rats hippocampus were analyzed quantitatively by electron microscope. Results： Compared with the control group, the Aβ group exhibited notably reduced synaptophysin expression and synaptic density（ P 〈 0.01 ）, accumulating the synaptic vesicles at the synaptic terminals abnormally and elongated the synaptic active zone under the electron microscope, in addition, the lost of small synapse is dominant. However, compared with the Aβ group, SVHRP group inhibited the descending of the level of synaptophysin and synaptic density and abnormal accumulating of the synaptic vesicles, and small synapses increated in number significantly（ P 〈 0.01 ）. Conclusion： These results strongly suggest that a direct causative role of Aβ in the synaptic degeneration seen in AD, SVHRP can inhibite Aβ-induced synaptie degeneration and it is possible as a treatment drug for Alzheimer＇s disease.

关 键 词：蝎毒液类 蝎毒耐热蛋白 淀粉样Β蛋白 阿尔茨海默病 海马 突触 突触体素 超微结构 大鼠 

分 类 号：R285.5[医药卫生—中药学]