9型腺相关病毒携带IL4对阿尔兹海默病模型大鼠学习记忆能力的影响

Effect of adeno-associated virus 9 carrying IL4 on learning and memory ability of Alzheimer’s disease model rats

目的探讨过表达白细胞介素4(IL4)的9型腺相关病毒(AAV9-IL4)对阿尔茨海默病(AD)模型大鼠在Morris水迷宫行为学测试中学习记忆的影响。方法75只SPF级SD大鼠,雄性,利用海马区注射Aβ1-42制作的AD模型;将模型随机分为实验组39只、对照组36只,尾静脉注射包装并测定好滴度的腺相关病毒(AAV9-IL4与AAV9空载对照),实验组大鼠尾静脉给予5μl AAV9-IL4注射,对照组大鼠给予等同剂量的AAV9空载注射。术后2 w,4 w,8 w分别采用Morris水迷宫测试,记录大鼠逃避潜伏期、经过原隐藏平台的次数以及大鼠在第1象限游泳时间占总体游泳时间的百分比。结果IL4-AAV9组SD大鼠逃逸潜伏期明显低于AAV9组SD大鼠(P<0.001)。IL4-AAV9组SD大鼠单位时间平均穿越平台次数显著高于AAV9组(F=109.23 P<0.001),且2 w、4 w差异显著,4 w、8 w无明显差异。IL4-AAV9组SD大鼠单位时间目标象限游泳时间占总时间比显著高于AAV9组,且2 w、4 w无明显差异,4 w、8 w差异显著。结论IL4-AAV9能够显著改善SD大鼠的空间学习记忆能力。

Objective To investigate the effects of type 9 adeno-associated virus(AAV9-IL4)over expression of interleukin-4 on learning and memory in Morris water maze behavior test in Alzheimer’s disease(AD)model rats.Methods 75 SD rats of SPF grade,male,were injected with Aβ1-42 into hippocampus to make AD model.The model was randomly divided into experimental group(n=39)and control group(n=36).The adeno-associated virus(AAV9-IL4 and AAV9 no-load control group)were packaged and measured by tail vein injection.The rats in the experimental group were injected with 5 U/L AAV9-IL4 through caudal vein,and the rats in the control group were injected with the same dose of AAV9 without loading.The control group was injected with the same dose of AAV9.Two weeks,four weeks and eight weeks after operation,Morris water maze test was used to record the escape latency,the times of passing through the original hidden platform and the percentage of swimming time in the first quadrant of the rats to the total swimming time.Results The escape latency of SD mice in IL4-AAV9 group was significantly lower than that in SD mice in AAV9 group(P<0.001),and the average times of crossing platform in SD mice in IL4-AAV9 group was significantly higher than that in AAV9 group(F=109.23 P<0.001).The difference was significant between 2 weeks and 4 weeks,but not between 4 weeks and 8 weeks.Swimming time of SD mice in the quadrant of unit time target in IL4-AAV9 group was significantly higher than that in AAV9 group,and there was no significant difference between2 weeks and 4 weeks,but not between 4 weeks and 8 weeks in SD mice.Conclusion IL4-AAV9 can significantly improve the spatial learning and memory ability of SD mice.