目的 基于 miR-124/SIRT1 信号通路探讨二至丸对神经突触损伤小鼠的作用及机制。方法 将 C57BL/ 6J 小鼠随机分为空白组、模型组、阴性病毒对照组、阳性药物组（白藜芦醇 50 mg•kg-1 •d-1 ）、二至丸组（3.5 g•kg-1 •d-1 ），每组 10 只。采用脑室注射 miR-124-UP 腺相关病毒复制 miR-124-UP 小鼠模型。灌胃给药，每日 1 次，连续 42 d。采用 Morris 水迷宫实验检测小鼠学习记忆能力；HE 及 Nissl 染色法观察海马组织病理 变化；检测血清丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-PX）水平；Western Blot 法检测海马组织中 SIRT1、BDNF、CREB、SYN、PSD95 蛋白表达水平；qPCR 法检测海马组织 miR-124、SIRT1、BDNF、CREB、SYN、PSD95 mRNA 表达水平。结果 与空白组比较，模型组小鼠第 5 天的逃避潜伏期显著延长（P＜0.01），穿越平台次数显著减少（P＜0.001）；小鼠海马 CA3 区神经细胞明显减少，细胞呈萎缩状态，细胞核浓染；血清 MDA含量显著升高（P＜0.001），GSH-PX 酶活性显著下降（P＜0.001）；海马组织 SIRT1、BDNF、CREB、SYN、PSD95 蛋白及 mRNA 表达量均显著下降（P＜0.05，P＜0.01，P＜0.001）；海马组织 miR-124 mRNA 表达量显著升高（P＜0.01）。与模型组比较，阳性药物组与二至丸组第 5 天的逃避潜伏期显著缩短（P＜0.01），穿越平台次数显著增加（P＜0.01，P＜0.001）；小鼠海马 CA3 区神经细胞数量增加，细胞形态趋于正常，萎缩细胞数量减少；血清 MDA 含量显著下降（P＜0.001），GSH-PX 酶活性显著升高（P＜0.01，P＜0.001）；海马组织 SIRT1、BDNF、CREB、PSD95 蛋白表达量均显著升高（P＜0.01，P＜0.001）；海马组织 miR-124 mRNA 表达量显著降低（P＜0.01），SIRT1、BDNF、CREB、SYN、PSD95 mRNA 表达量均显著升高（P＜0.05，P＜0.01，P＜0.001）；二至丸组小鼠海马组织 SYN 蛋白表达量显著升高（P＜0.001）。结论 二至丸能够提高 miR-124-UP 小鼠的学习记忆能力，增强抗氧化应激能力，改善神经元损伤，可能与其通过 miR-124/SIRT1 信号通路调控神经元可塑性有关。

Objective To investigate the effect and mechanism of Erzhi Pills on synaptic damage of mice based on miR-124/SIRT1 signaling pathway. Methods C57BL/6J mice were randomly divided into blank group， model group，negative viral control group，positive drug group （resveratrol 50 mg•kg-1 •d-1），and Erzhi Pills group （3.5 g•kg-1 •d-1），with 10 mice in each group. A miR-124-UP mouse model was replicated using intraventricular injection of adenovirus. The corresponding drug was administered by gavage after modeling，once a day for 42 days. Morris water maze was used to detect the learning and memory ability of the mice. Pathological changes in hippocampal tissue were observed using HE and Nissl staining. The kits were used to detect the serum levels of malondialdehyde （MDA） and glutathione peroxidase （GSH-PX） . Western Blot was used to determine the protein expression of SIRT1，BDNF，CREB，SYN and PSD95 in hippocampal tissues， and qPCR was used to determine the mRNA expression of miR-124， SIRT1，BDNF，CREB，SYN and PSD95 in hippocampal tissues. Results Compared with the blank group，escape latency at the 5th day of the model group was significantly prolonged （P＜0.01）， while the number of crossing platforms was significantly reduced （P＜0.001） . Nerve cells in the CA3 region of the hippocampus were markedly reduced，with atrophied cells and densely stained nuclei. Serum MDA content was markedly up-regulated （P＜0.001），and GSH-PX enzyme activity appeared to be significantly down-regulated （P＜0.001） . The protein and mRNA expression of SIRT1，BDNF，CREB，SYN，and PSD95 in hippocampal tissue appeared significantly down-regulated （P＜0.05，P＜0.01， P＜0.001）， but the mRNA expression of miR-124 in hippocampal tissue was significantly up-regulated（P＜0.01） . Compared with the model group，escape latency at the 5th day of positive drug group and Erzhi Pills group was obviously shortened （P＜0.01） and the number of crossing platforms was significantly increased （P＜0.01，P＜0.001） . Nerve cells in the CA3 region of the hippocampus was increased，the cell morphology tended to be normal， and the number of atrophic cells was decreased. The serum MDA content was significantly down-regulated （P＜0.001）， and the GSH-PX enzyme activity was significantly up-regulated （P＜0.01， P＜0.001） . The protein expression of SIRT1， BDNF， CREB， SYN， and PSD95 in hippocampal tissue was significantly up-regulated （P＜0.01， P＜0.001） . The mRNA expression of miR-124 in hippocampal tissue was significantly down-regulated （P＜0.01） . The mRNA expression of SIRT1，BDNF，CREB，SYN and PSD95 in hippocampal tissue was significantly up-regulated （P＜0.05， P＜0.01， P＜0.001） . The protein expression of SYN in hippocampal tissue of Erzhi Pills group was significantly increased （P＜0.001） . Conclusion Erzhi Pills could improve the learning and memory ability，enhance anti-oxidative stress and ameliorate neuronal cell damage in miR-124-UP mice，which may be related to the regulation neuronal plasticity through the miR-124/SIRT1 signaling pathway.

R285.5

广东省自然科学基金面上项目（2019A1515011299）