神经调节素对阿尔茨海默病大鼠模型海马细胞凋亡和核转录因子κB表达的影响

Effect of neuregulin on expressions of apoptosis and nuclear factor kappa B in hippocampus of Alzheimer＇s disease model rats

目的研究神经调节素1β（neuregulin1β，NRG1β）对β-淀粉样蛋白1-40（beta-amyloid prorein，Aβ1-40）所致的模拟阿尔茨海默病模型大鼠空间学习记忆能力、神经元凋亡、核转录因子KB（nuclear factor kappaB，NFKB）表达的影响，探讨NRG改善学习记忆能力的作用机制。方法成年健康雄性Wistar大鼠30只，随机数字表法分为对照组、模型组和治疗组，每组10只，经侧脑室微量注射Aβ1-40建立实验性阿尔茨海默病模型大鼠，经侧脑室注射NRG1β（0．3ug·kg-1）干预治疗。各组大鼠实验前及造模7d后、治疗14d后均用Y型迷宫检测大鼠学习和记忆功能，利用HE染色观察海马神经细胞的结构变化，原位TUNEL法检测海马神经细胞凋亡，免疫组织化学法检测海马神经细胞NFKB的表达。结果模型组大鼠学习能力[（57．50±1．58）次]和记忆能力[（7．20±1．03）次]较对照组学习[（59．50±2．79）次]和记忆能力[（7．50±1．08）次]明显下降（t=20．36，5．28，P〈0．05），海马区神经细胞排列稀疏、紊乱，有明显神经元脱失，TUNEL阳性细胞数明显增多、NFKB表达增加（P〈0．05）。NRG1β治疗组大鼠学习记忆能力[（67．70±4．90）次，（5．80±0．63）次]及细胞结构较模型组[（79．10±4．12）次，（4．40±0．69）次]显著改善（t=5．63，4．69，P〈0．05）。相对于模型组[（41．10±7．95）次，（29．30±7．24）个]，NRG1β治疗组NFKB表达（25．90±6．67）明显减弱、细胞凋亡数量[（23．50±3．89）个]明显减少（t=4．63，2．23，P〈0．05）。结论NRG1β能抑制海马神经细胞NFKB表达，减少细胞凋亡，从而改善阿尔茨海默病大鼠的学习和记忆能力。

Objective To investigate the effect of neuregulin1β （NRG1β）on the learning memory abilities and the neuronal apoptosis and the expressions of nuclear factor kappa B （NFKB） in experimental Alzheimer＇s disease model in rats induced with beta-amyloid proteinl-40 （Aβ1-40 ） injection. To explore the mechanisms of NRG in improving the capabilities of learning and memory. Methods Thirty adult healthy male wistar rats were randomly divided into control group （n= 10）,model group （n = 10） and treated group （n = 10）. Alzheimer＇s disease models were established by stereotactically injecting Aβ1-40 into the left lateral ventricle,and treated by injecting NRG1β（0.3 ug . kg-1 ） into the right lateral ventricle. The learning and memory abilities of rats were evaluated with Y-electric maze before the experiment and 7 days after making Alzheimer＇s disease models and 14 days after treatment. HE staining was used to observe the structure of hippocampal neurons. The neuronal apoptosis of hippocampus was investigated by TUNEL assay. The expressions of NFKB in hippocampal neurons were determined with immunohistochemistry technique. Results Compared with control group （57.50 ± 1.58,7.20 ± 1.03 ） ,the model group rats （59.50 ± 2.79,7.50 ± 1.08 ） showed low cognitive ability （ t = 20.36,5.28, P 〈 0.05 ） , the hippocampal pyramidal ceils of rats in the model group were sparse and disturbed pyramidal cells , noticeable neuron loss. The number of neuronal apoptosis and the expressions of NFKB increased significantly than those in control group （P 〈 0.05 ）. Compared with model group （79.10 ± 4.12,4.40 ± 0.69 ）, NRG1β strikingly improved cognitive ability （67.70 ± 4.90,5.80 ± 0.63 ） and normal cell structure （ t = 5.63,4.69, P 〈 0.05 ）. The expressions of NFKB（25.90 ± 6.67 ） reduced while the number of neuronal apoptosis （ 23.50 ± 3.89 ） decreased markablely than those （ 41. 10 ± 7. 95, 29. 30 ± 7. 24） in model group（t = 4. 63, 2. 23, P 〈 0. 05）. Conclusion NRG1 β might decrease the neuronal apoptosis by inhibiting NFKB expressions, so that to improve the learning and memory abilities of experimental dementia rats.