人源化抗Aβ抗体治疗APP/PS1转基因鼠的实验研究

Experiment research of APP /PS1 transgenic mice's treatment with humanization anti-amyloid-β antibodies

目的初步探讨人源化抗Aβ抗体对APP/PS1转基因鼠被动免疫治疗效果。方法选取36只APP/PS1转基因鼠,随机分为3组,每组各12只,分别予腹腔注射人源化抗Aβ抗体、鼠源性单克隆抗体、磷酸盐缓冲液(PBS),观察3组小鼠脑内淀粉样斑块积聚情况,测试其学习记忆能力,同时检测血清及脑内TNF-α含量。结果人源化抗Aβ抗体组、鼠源性单克隆抗体组小鼠空间辨别学习记忆能力均优于PBS对照组(P<0.05),人源化抗Aβ抗体组与鼠源性单克隆抗体组间比较差异无统计学意义(P>0.05);治疗后人源化抗Aβ抗体组与鼠源性单克隆抗体组小鼠大脑皮质、海马区棕色斑块沉积明显形态变小、数量变少、范围分散。人源化抗Aβ抗体组与鼠源性单克隆抗体组脑内TNF-α含量均较PBS对照组明显减少(P<0.05)。结论人源化抗Aβ抗体治疗转基因小鼠后明显改善其学习记忆能力,同时使其脑内TNF-α含量减少。

Objective To preliminarily explore the effect of passive immunity treatment for APP/PS1 transgenic mice with humanization anti-amyloid-βantibodies.Method Thirty-six APP/PS1 transgenic mice were selected and randomly divided into 3 groups.Experimental group（n=1 2）was intraperitoneal injected with humanization anti-amyloid-βantibodies,positive control group was intraperitoneal injected with monoclonal an-tibody,negative control group was intraperitoneal injected with PBS.The accumulation of the amyloid plaques in the brain and the ability of learning and memory were observed.The levels of TNF-αin serum and brain were detected.Result The mice’s ability of learning and memory in space identification of experimental group and positive control group,were statistically better than that of negative control group （P〈0.05）.However, there is no statistically difference between experimental group and positive control group （P〉0.05）.With the treatment of humanization anti-amyloid-βantibodies and monoclonal antibody ,the brown plaque deposition in mice’s brain cortex and hippocampus were obviously smaller,with less number and dispersive range.The levels of TNF-αin brain in experimental group and positive control group decreased significantly when compared with negative control group （P〈0.05）.Conclusion For transgenic mice,humanization anti-amyloid-βantibod-ies could obviously improve their learning and memory ability,and increase the level of TNF-αin brain.