切除大网膜对阿尔茨海默病小鼠的神经保护作用

Neuroprotective effect of omentum removal on Alzheimer's mice

目的 探讨大网膜对阿尔茨海默病(Alzheimer’s disease, AD)认知障碍及β淀粉样蛋白(amyloid β,Aβ)负荷的影响。方法 选取3月龄转基因和野生型雌鼠各6只分别为转基因组和野生型组,选取6只3月龄转基因雌鼠,手术切除大网膜,建立转基因-大网膜切除(OR)组,各组小鼠9月龄时采用Morris水迷宫进行定位航行和空间探索实验,采用6E10抗体免疫组织化学染色和刚果红染色检测脑内Aβ,采用刚果红染色检测小鼠脑淀粉样血管病(CAA)。采用普鲁士蓝染色检测小鼠脑内微出血。采用抗神经元核抗原(NeuN)+神经元轴突抗体(MAP2)抗体双重标记免疫荧光检测小鼠脑内神经元与轴突。结果 转基因-OR组逃逸潜伏期和逃逸距离明显低于转基因组,但明显高于野生型组,穿越平台时间明显高于转基因组(P<0.05)。转基因-OR组刚果红和6E10抗体免疫组织化学染色阳性总面积、刚果红和6E10抗体染色阳性颗粒数明显低于转基因组[(0.20±0.02)%vs(0.50±0.04)%,(0.85±0.05)%vs(1.65±0.04)%,(21.65±1.52)个/mm^(2)vs(39.05±1.65)个/mm^(2),(56.75±4.21)个/mm^(2)vs(74.94±2.92)个/mm^(2),P<0.05],但明显高于野生型组(P<0.05)。转基因-OR组CAA面积和CAA计数、脑微出血计数明显低于转基因组,NeuN、MAP2抗体总面积明显高于转基因组(P<0.05)。结论 切除大网膜减轻AD小鼠空间学习记忆能力损害,减少脑内Aβ负荷,抑制AD特征性病理改变,提示大网膜在AD发生发展中可能起着重要作用。

Objective To explore the effect of the great omentum on cognitive impairment and brain β amyloid(Aβ)burden in mouse model of Alzheimer's disease(AD).Methods Six 3-month-old APP/PS1transgenic female mice and 6female wide-type(WT)mice were adopted in this study.The greater omentum was surgically removed(OR)in the transgenic(Tg)female mice to establish the Tg-OR group,and Tg and WT female mice were set as controls.Morris water maze test was conducted for the spatial learning and memory abilities of mice.The Congo red and 6E10immunohistochemical staining were used to evaluate the Aβlevel in the brain.Congo red staining was used to observe cerebral amyloid angiopathy(CAA),and Prussian blue staining was employed for cerebral microhemorrhage in the mice.Cerebral neurons and axons were detected with the expression of NeuN and microtubule-associated protein 2(MAP2)by double immunofluorescence assay.Results The Tg-OR group obtained significantly shorter escape latency and escape distance than the Tg group,but longer than the WT group,and longer time of crossing the platform than the Tg group(all P<0.05).Percentages of Congo red[(0.20±0.02)%vs(0.50±0.04)%]and 6E10antibody[(0.85±0.05)%vs(1.65±0.04),P<0.05]positive areas and numbers of Congo red-stained[(21.65±1.52)/mm^(2) vs(39.05±1.65)/mm^(2)]and 6E10antibody stained plaques[(56.75±4.21)/mm^(2) vs (74.94±2.92)/mm^(2)]in the Tg-OR group were obviously lower than those of the Tg group(P<0.05),but notably higher than those of the WTgroup(P<0.05).The area and number of CAA,and the number of cerebral microbleeds in theTg-OR group were decreased when compared with those in the Tg group.The double positive area of NeuN and MAP2was larger in the Tg-OR group than the Tg group(P<0.05).ConclusionRemoval of the greater omentum can alleviate the impairment of spatial learning and memoryabilities,reduce the Aβburden,and suppress typical pathological changes of AD,suggesting thatthe greater omentum may play an important role in the pathogenesis of the disease.