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目的 研究突变的人载脂蛋白 E(apo E)对大脑皮层功能的影响。方法 以 F1代 apo E4与 apo E7转基因小鼠为研究对象 ,分别用 Southern印迹分析及 EL ISA检测人 apo E基因在 F1代小鼠染色体上的整合与在血中的表达 ;以主动回避实验检测小鼠的学习能力和短期与长期记忆能力的变化 ,同时用酶法测定 F1代小鼠的血脂水平。结果 (1)人 apo E4和 apo E7基因稳定地整合于 F1代小鼠染色体上并高效表达于血清中 ;(2 ) F1代小鼠血脂升高的同时 ,apo E4小鼠学习能力与短期记忆能力均显著下降 ,apo E7小鼠短期记忆能力也下降。结论 人apo E4与 apo E7基因过度表达均可使转基因小鼠大脑皮层功能受损害 ,提示人 apo E基因突变可能与 apo E4表型一样 ,也与早老性痴呆的发病有一定关系。
Aim To investigate the effect of mutant human apolipoprotein E on cerebral cortex function. Methods The F1 generation of apo E4 and apo E7 transgenic mice were studied by Southern blot analysis and ELISA, respectively. The integration and the expression of human apo E gene in the F1 generation of mouse chromosomes were detected by the active avoidance assay Mice learning ability and short-term and long-term changes in memory capacity, while using enzyme method to determine the F1 generation of blood lipid levels in mice. Results (1) The human apo E4 and apo E7 genes were stably integrated in the chromosomes of F1 generation mice and expressed in the serum. (2) In addition to the elevated blood lipids in the F1 generation mice, the learning ability of apo E4 mice was associated with short-term memory Ability were significantly decreased, apo E7 mice also short-term memory capacity decreased. CONCLUSION: Overexpression of apo E4 and apo E7 genes can impair the function of cerebral cortex in transgenic mice, suggesting that human apo E gene mutation may be the same as apo E4 phenotype and also have a certain relationship with the pathogenesis of Alzheimer’s disease.