【摘要】 目的:探讨经颅内注射β-淀粉样蛋白(Aβ)1-42单克隆抗体(mAb)对阿尔茨海默病(AD)大鼠的疗效及机制。方法:30只SD大鼠分3组:AD模型组和治疗组各12只,生理盐水组6只。AD模型组和治疗组于侧脑室注入Aβ1-42蛋白片段建立AD大鼠模型,治疗组大鼠在注射后第14天于侧脑室内注入Aβ1-42mAb,连用3d。采用水迷宫法检测大鼠认知能力;取脑组织采用RT-PCR和免疫组织化学法检测Aβ、乙酰胆碱转移酶(ChAT)基因和蛋白。结果:3组大鼠逃避潜伏期比较,差异有统计学意义(F=23.117,P<0.01),且治疗组大鼠短于AD模型组(P<0.05)。治疗组较AD模型组大鼠脑组织中AβmRNA水平减少,ChATmRNA水平增加;3组大鼠脑组织中Aβ和ChAT蛋白表达比较,差异有统计学意义(F=338.900和83.490,P均<0.001),治疗组大鼠脑组织Aβ蛋白的表达低于AD模型组,ChAT蛋白的表达高于AD模型组(P<0.05)。结论:Aβ1-42mAb可改善AD大鼠的认知功能,其机制可能与抗原抗体结合减少Aβ积聚并调节ChAT活性有关。更多还原

【Abstract】 Aim:To explore the effects and mechanism of Aβ1-42 monoclonal antibody(mAb)on cognitional ability in Alzheimer’s disease(AD)rats.Methods:A total of 30 SD rats were divided into 3 groups:AD model group(12 rats),treatment group(12 rats)and normal saline group(6 rats).Rats in AD model and treatment groups were made AD model with injection of Aβ1-42 peptide.Rats in treatment group were injected Aβ1-42 mAb through right side ventricle at 14th day after induced injection.Cognitional memory ability was tested by Morris water maze test,and the expression of Aβ and ChAT in brain tissue were examined by RT-PCR and immunohistochemistry.Results:Cognitional ability of rats among the 3 groups had siginificant differences(F=23.117,P<0.001),which improved in treatment group compared with AD moldel group(P<0.05).The contents of Aβ and ChAT protein in brain tissues among the 3 groups had siginificant differences(F=338.900 and 83.490,P<0.001).The expression of Aβ in treatment group were lower than that in AD model group,but the expression of ChAT was the opposite.Conclusion:Aβ1-42 mAb has obvious curative effect on AD model rats,which could reduce the accumulation of Aβ and adjust the avtivity of ChAT.更多还原