目的 探讨调补心肾方（党参、制首乌、枸杞子、黄芪等）对阿尔茨海默病 5xFAD 转基因小鼠突触可塑 性的影响及机制。方法 取 5 月龄雄性野生型（WT）小鼠和 5xFAD 转基因小鼠各 18 只，分别随机分为对照组 （0.9% NaCl）、调补心肾方组（颗粒剂，4.18 g·kg-1）、安理申组（盐酸多奈哌齐，0.625 mg·kg-1），每组 6 只。按 照上述分组灌胃给药，每日 1 次，共 60 d。采用透射电镜观察小鼠海马组织超微结构；Western Blot 法检测小 鼠皮层组织中 Synaptophsin、PSD-95、p-NMDAR1、NMDAR1、p-CaMKⅡa、CaMKⅡa、PI3K、p-Akt、Akt、 p-mTOR、mTOR 蛋白表达水平。结果 与 WT 对照组比较，5xFAD 对照组小鼠海马 CA1 区突触的超微结构不 规则，线粒体萎缩、减少，线粒体嵴断裂、消失，突触膜弯曲不规则，突触囊泡减少，突触后致密物（PDS）变 薄甚至断裂；皮层组织中 Synaptophsin、PSD-95、p-NMDAR1/NMDAR1、p-CaMKⅡa/CaMKⅡa、PI3K、p-Akt/ Akt、p-mTOR/mTOR 蛋白表达均明显下调（P＜0.05）。与 5xFAD 对照组相比较，5xFAD 调补心肾方组小鼠海马 CA1 区突触的超微结构有明显变化，线粒体数量增加，突触囊泡增多，突触膜完整，突触后致密物有增厚现 象；皮层组织中 Synaptophsin、PSD-95、p-NMDAR1/NMDAR1、p-CaMKⅡa/CaMKⅡa、PI3K、p-Akt/Akt、 p-mTOR/mTOR 蛋白表达明显上调（P＜0.05）。结论 调补心肾方可能通过活化 PI3K/Akt/mTOR 通路，促进突 触可塑性相关蛋白合成，进而改善 AD 的认知功能障碍。

Objective To investigate the effect and mechanism of Tiaobu Xinshen Prescription （Codonopsis Radix， Polygoni Multiflori Radix Praeparata， Lycii Fructus， Astragali Radix， etc.） on synaptic plasticity in 5xFAD transgenic mice with Alzheimer’s disease （AD） . Methods Eighteen 5-month-old male wild-type （WT）mice and 18 5xFAD transgenic mice were randomly divided into control group （0.9% NaCl）， Tiaobu Xinshen Prescription group （granules，4.18 g·kg-1） and Aricept group （Donepezil Hydrochloride，0.625 mg·kg-1），with six mice in each group. According to the above groups，the rats were given intragastric administration once a day for 60 days. The ultrastructure of hippocampus in mice was observed by transmission electron microscopy. Western Blot was used to detect the protein expression levels of Synaptophsin，PSD-95，p-NMDAR1，NMDAR1，p-CaMKIIa，CaMKIIa， PI3K，p-Akt，Akt，p-mTOR and mTOR in mouse cortical tissue. Results Compared with the WT mice control group，the ultrastructure of synapses in the hippocampal CA1 region of the 5xFAD control group was irregular，the mitochondria was atrophied and reduced， the mitochondrial cristae was broken and disappeared， the synaptic membrane was irregularly and curved，the synaptic vesicles were reduced，and the postsynaptic density （PDS） was thinned or even broken. The protein expressions of Synaptophsin，PSD-95，p-NMDAR1/NMDAR1，p-CaMKIIa/ CaMKIIa， PI3K， p-Akt/Akt and p-mTOR/mTOR in the cortex were significantly down-regulated （P＜0.05）. Compared with the mice in the 5xFAD control group，the ultrastructure of synapses in the hippocampal CA1 region of the mice in the Tiaobu Xinshen Prescription 5xFAD group was significantly changed，the number of mitochondria was increased， the number of synaptic vesicles was increased， the synaptic membrane was intact， and the postsynaptic density was thickened. The protein expressions of Synaptophsin， PSD-95， p-NMDAR1/NMDAR1， p-CaMKIIa/CaMKIIa， PI3K， p-Akt/Akt and p-mTOR/mTOR in the cortex were significantly up-regulated （P＜ 0.05）. Conclusion Tiaobu Xinshen Prescription may promote the synthesis of synaptic plasticity-related proteins by activating the PI3K/Akt/mTOR pathway，thereby improving the cognitive dysfunction of AD.

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福建省自然科学基金项目（2022J01258）；“十四五”非中医医疗机构中医药科室建设项目（2128101401，2100601）；第五批医院重点 学科建设经费项目（中医科，2022YYZDXK16）