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目的:研究还脑益聪方提取物对不同月龄APP转基因小鼠行为学及其海马CA1区线粒体超微结构的影响,从能量代谢的角度探讨中药提取物治疗AD的部分作用机制。方法:选用3月龄APP695V717I转基因小鼠120只为痴呆模型,随机分为模型组、盐酸多奈哌齐组、还脑益聪方提取物高剂量组、低剂量组,每组30只,并设正常对照组。采用Morris水迷宫及跳台实验观察试验动物的行为学;应用透射电镜观察模型脑海马区线粒体超微结构。结果:7,9月龄APP转基因模型小鼠Morris水迷宫试验中穿越原平台位置次数、游泳时间和路程均较转基因模型组显著增多(P<0.05,P<0.01)、跳台实验中的潜伏期均明显缩短(P<0.01),且随着病程的进展而有加重之势。还脑益聪方提取物能明显提高不同月龄转基因小鼠穿越原平台位置次数、游泳时间和路程(P<0.05,P<0.01),且明显延长跳台实验中的潜伏期(P<0.05,P<0.01)。7,9月龄APP转基因小鼠海马CA1区神经元线粒体均表现出线粒体膜破坏、溶解,内嵴大部分排列轻度紊乱,有的嵴内腔扩张,基质疏松,线粒体肿胀,且随病程进展而损坏加重;还脑益聪方提取物能改善不同月龄APP转基因小鼠海马CA1区线粒体超微结构与数量。结论:APP转基因小鼠AD模型学习记忆能力显著下降,且该模型海马CA1区神经元线粒体数量减少、结构损伤,且随病程进展而均显加剧;还脑益聪方提取物能够改善不同病程APP转基因小鼠的学习记忆能力,其可能与改善海马区神经元线粒体结构、增加线粒体数量而保护脑功能有关。
OBJECTIVE: To study the effects of Huannao Yicong Fang extract on the behavior and the ultrastructure of mitochondria in hippocampal CA1 region of APP transgenic mice at different ages, and to explore the mechanism of action of traditional Chinese medicine extract on AD in terms of energy metabolism. Methods: A total of 120 APP695V717I transgenic mice, 3 months old, were randomly divided into model group, donepezil hydrochloride group, high-dose and low-dose group of Huannao Yike Decoction, 30 rats in each group. Normal control group. Morris water maze and jumping test were used to observe the behavior of experimental animals. Transmission electron microscopy was used to observe the ultrastructure of mitochondria in hippocampus. Results: The frequency of swimming through the original platform, the swimming time and the distance in the Morris water maze test of APP transgenic mice at 7 and 9 months were significantly higher than those in the transgenic model (P <0.05, P <0.01) Significantly shortened (P <0.01), and with the progression of the disease there is an aggravating trend. Huannao Yicongfang extract can significantly increase the number of transplants, swimming time and distance across the original platform (P <0.05, P <0.01), and significantly prolong the incubation period (P <0.05, P <0.01). Mitochondria of hippocampal CA1 neurons in APP transgenic mice at 7 and 9 months of age showed mitochondrial membrane destruction and lysis. Most of the internal cristae were arranged in mild disorder, and some of the crista lumen dilated, the matrix was loose and the mitochondria were swollen. With the progression of the disease While the damage was aggravated. Huannao Yicong Fang extract could improve the ultrastructure and quantity of mitochondria in hippocampal CA1 region of APP transgenic mice at different months. CONCLUSION: Learning and memory abilities of APP transgenic mice decreased significantly, and the number of mitochondria in hippocampal CA1 subfields decreased and their structures were damaged. The learning and memory abilities of transgenic mice may be related to improving the mitochondrial structure of neurons in the hippocampus, increasing the number of mitochondria and protecting brain function.