非遗传性阿尔茨海默病大鼠模型建立的实验研究

Establishment of rat model of non-hereditary Alzheimer's disease

目的:应用喹啉酸损毁Meynert基底核建立非遗传性阿尔茨海默病大鼠模型。方法:应用喹啉酸(每侧150nmol,2μL)损毁老年大鼠双侧Meynert基底核,一次性训练被动回避跳台实验和水迷宫空间分辨能力测试,研究大鼠学习记忆的改变,并观察1,2,3,4四氢吖啶(THA)对Meynert基底核损毁大鼠学习记忆的改善作用。结果:与假损伤组相比,喹啉酸损伤Meynert基底核后13d,大鼠在跳台中出现的错误反应次数明显增多,学习中为(1.25±0.71)次比(3.75±1.28)次(q=6.83,P<0.01),重测验中为(0.50±0.53)次比(2.00±0.76)次(q=7.42,P<0.001)。损伤后16d,大鼠学会迷宫所需的训练次数显著增加(q=22.16,P<0.001)。与喹啉酸组对比,腹腔注射THA10mg/(kg·d)13d后,Meynert基底核损伤后大鼠在跳台中出现的错误反应次数明显减少(P<0.01),腹腔注射THA16d后学会迷宫所需的训练次数也显著减少(q=20.38,P<0.01)。结论:喹啉酸损毁老年大鼠双侧Meynert基底核,能够建立非遗传性阿尔茨海默病大鼠模型。目的:应用喹啉酸损毁Meynert基底核建立非遗传性阿尔茨海默病大鼠模型。方法:应用喹啉酸(每侧150nmol,2μL)损毁老年大鼠双侧Meynert基底核,一次性训练被动回避跳台实验和水迷宫空间分辨能力测试,研究大鼠学习记忆的改变,并观察1,2,3,4四氢吖啶(THA)

AIM:To establish rat models of non-hereditary Alzheimer's disease(AD) by dama ging bilateral nucleus basalis of Meynert(NBM) with quinolinic acid. METHODS:Bilateral NBM of elderly rats were damaged with quinolinic acid(150 nm ol in 2 μL for each NBM).One-off step-down passive avoidance training and wat er-maze spatial localization task were conducted to observe the ability of lear ning and memory in the rats .The effects of 1,2,3,4-tetrahydroacridine(THA)on learning and memory of the rat with damaged NBM were also observed. RESULTS:Compared with the sham-lesion group,the number of errors in the step -down trial 13 days after NBM damage was increased significantly(in the learnin g test,1.25±0.71 vs 3.75±1.28,q=6.83,P< 0.01;in the retest, 0.50±0.53 vs 2.00 ±0.76,q=7.42,P< 0.001). So was the training times to reach the criterion in the water-maze task 16 days after damage(q= 22.16,P< 0.001).Compared with the qui nolinic acid group, the number of errors in the step-down trial after the rats were intraperitoneally injected with THA 10 mg/(kg·d ) for 13 days was decrease d obviously(P< 0.01) .So was the training times to reach the criterion in the wa ter maze task 16 days after intraperitoneal injection of THA(q= 20.38,P< 0.01). CONCLUSION: Rat models of non-hereditary AD can be made by damaging bilateral NBM with quinolinic acid.