Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China.
Department of Traditional Chinese Medicine, Affiliated Hospital of Binzhou Medical College, Shandong 256603, China.
J Tradit Chin Med. 2023 Feb;43(1):78-86. doi: 10.19852/j.cnki.jtcm.20220727.001.
To investigate the efficacy of Jinsiwei (a patented Chinese herbal compound) on learning and memory impairment, the number of synapses and synaptic plasticity-related structural and functional protein expression in mice with sporadic Alzheimer's disease (SAD) induced by streptozotocin.
Seventy-five C57/BL6J male mice were intracerebroventricularly injected with streptozotocin to establish the animal model of SAD. Mice were randomly divided into the model group (MG), donepezil group (DG), and the Jinsiwei high, medium, and low-dose groups (JH, JM, JL). Another fifteen C57/BL6J male mice were injected with artificial cerebrospinal fluid as the control group (CG). The intervention groups were intragastrically administrated with corresponding medicine, while the CG and MG were given 0.5% carboxymethyl cellulose by gavage. After 3 months, the Morris Water Maze test and step-down passive avoidance test were used to assess the learning and memory ability of mice. Synapses in hippocampal CA1 were observed by transmission electron microscope. Immunohistochemistry and western blotting were used to assess the distribution and expression levels of synaptic plasticity-related structural and functional proteins involving drebrin, cofilin, synapsin (syn), and N-methyl D-aspartate receptor subtype 2B (NR2B).
The Morris Water Maze results showed that the escape latency in the Jinsiwei intervention groups was significantly shorter than that of the MG. Results of the step-down passive-avoidance test showed that the error times in the Jinsiwei intervention groups were significantly reduced compared with the MG. Transmission electron microscope results showed that the number of synapses in hippocampal CA1 was obviously increased in the Jinsiwei intervention groups compared with the MG. Immunohistochemical and western blotting results revealed that the positive cells and expression levels of drebrin, syn, and NR2B were significantly decreased in the MG and meanwhile cofilin significantly increased, while these changes were reversed after the Jinsiwei treatment.
Jinsiwei can alleviate learning and memory impairments in a mouse model of SAD, increase the number of synapses and enhance synaptic plasticity rescuing the expression of drebrin, syn, and NR2B and inhibiting cofilin expression.
观察金实维对链脲佐菌素诱导的散发性阿尔茨海默病（SAD）模型小鼠学习记忆能力、突触数量及突触可塑性相关结构和功能蛋白表达的影响。
75 只雄性 C57/BL6J 小鼠立体定位侧脑室注射链脲佐菌素（STZ）制备 SAD 模型，随机分为模型组（MG）、多奈哌齐组（DG）和金实维高、中、低剂量组（JH、JM、JL），每组 15 只，另取 15 只 C57/BL6J 雄性小鼠作为空白对照组（CG），CG 和 MG 组给予 0.5%羧甲基纤维素钠灌胃，干预组给予相应药物灌胃，连续给药 3 个月后，采用 Morris 水迷宫和避暗实验检测各组小鼠学习记忆能力，透射电镜观察海马 CA1 区突触数量，免疫组化和 Western blot 检测突触可塑性相关结构和功能蛋白 drebrin、cofilin、突触素（syn）和 N-甲基-D-天冬氨酸受体 2B 亚型（NR2B）的分布和表达水平。
Morris 水迷宫实验结果显示，金实维干预组逃避潜伏期明显短于 MG 组；避暗实验结果显示，金实维干预组错误次数明显少于 MG 组；电镜结果显示，金实维干预组海马 CA1 区突触数量明显多于 MG 组；免疫组化和 Western blot 结果显示，MG 组 drebrin、syn 和 NR2B 阳性细胞数及蛋白表达水平明显降低，cofilin 蛋白表达水平明显升高，金实维治疗后上述变化均得到逆转。
金实维可改善 SAD 模型小鼠学习记忆能力，增加突触数量，增强突触可塑性，其机制可能与上调 drebrin、syn 和 NR2B 表达、下调 cofilin 表达有关。
