目的:基于HIF1‑VEGF‑Notch通路探讨夏天无（Rhizomes of Corydalis Decumbens，RCD）改善血管性痴呆（vascular dementia，VD）模型大鼠学习记忆能力的可能作用机制。 方法:运用改良双侧颈总动脉结扎（bilateral vessel occlusion，2‑VO）法构建血管性痴呆大鼠模型，将SD大鼠随机分为假手术（Sham）组、VD组、尼莫地平（Nimodipine，Nim，0.01 g/kg）组及夏天无低、中、高剂量（RCD‑L、RCD‑M、RCD‑H，剂量分别为0.2、0.4、0.8 g/kg）组，每组14只，持续灌胃40 d。通过Morris水迷宫实验检测学习记忆能力，尼氏染色观测神经元数量及形态变化，免疫组化观察微血管密度（microvessel density，MVD）变化及血管内皮生长因子受体（vascular endothelial growth factor receptor，VEGFR）的表达差异，Western blot检测缺氧诱导因子1α（hypoxia inducible factor‑1α，HIF‑1α）、血管内皮生长因子（vascular endothelial growth factor，VEGF）和跨膜受体蛋白Notch1（notch homolog 1，Notch1）的蛋白表达水平。 结果:与Sham组相比，VD组大鼠平均逃避潜伏期明显延长（P<0.05），穿越平台次数明显减少（P<0.01）；CA1区锥体细胞坏死现象明显，数量明显减少（P<0.01）；MVD增加（P<0.05），VEGFR蛋白表达水平明显升高（P<0.05）；脑组织HIF‑1α、VEGF及Notch1蛋白含量升高（P<0.05）。与VD组比较，各治疗组大鼠逃避潜伏期均不同程度缩短（P<0.05），穿越平台次数明显增多（P<0.05）；各治疗组神经元数量及MVD增加（P<0.05），VEGFR、HIF‑1α、VEGF及Notch1蛋白表达明显升高（P<0.05）。 结论:夏天无在一定程度上能改善VD大鼠的认知障碍，增强学习记忆能力，其作用机制可能与其调节HIF1‑VEGF‑Notch信号通路，诱导脑组织血管新生，增加MVD，恢复血氧供应，修复神经元损伤有关。

Objective:To explore the possible mechanisms of action of Rhizomes of Corydalis Decumbens （RCD） in improving the learning memory capacity of rats in a vascular dementia （VD） model based on the HIF1‑VEGF‑Notch pathway. Methods:A vascular dementia rat model was constructed using the improved bilateral vessel occlusion method （2‑VO）. SD rats were randomly divided into the sham surgery （Sham） group， the model （VD） group， the nimodipine （Nimodipine， Nim， 0.01 g/kg） group， and the Rhizomes of Corydalis Decumbens low dose， medium dose and high dose （RCD‑L， RCD‑M， RCD‑H， doses were 0.2， 0.4， 0.8 g/kg） groups， with 14 rats in each group， and continued gavage for 40 days. Learning memory ability was detected by Morris water maze experiment. Neuronal number and morphological changes were observed by Nissl staining. Changes in microvessel density （MVD） and differences in vascular endothelial growth factor receptor （VEGFR） expression were observed by immunohistochemistry. The protein convey level of hypoxia inducible factor‑1α （HIF‑1α）， vascular endothelial growth factor （VEGF） and notch homolog 1 （Notch1） were detected by Western blot. Results:Compared to the Sham group， the VD group rats dramatically elongate mean escape latency （P<0.05）， cross platform noticeably diminish （P<0.01）. The necrosis phenomenon of pyramidal cells in CA1 area is significant， and the number shows a very significant decrease （P<0.01）. The MVD increased （P<0.05）， VEGFR protein convey levels noticeably diminish （P<0.05）. The content of brain tissue HIF‑1α， VEGF and Notch1 proteins increased （P<0.05）. Compared to the VD group， the escape latency of rats in each treatment group was shortened to varying degrees （P<0.05）， times of platform crossing was markedly increased （P<0.05）. The number of neurons and MVD increased in each treatment group （P<0.05）， and the expression levels of VEGFR， HIF‑1α， VEGF and Notch1 proteins were significantly increased （P<0.05）. Conclusion:Rhizomes of Corydalis Decumbens can improve cognitive impairment and enhance learning and memory abilities in VD rats to a certain extent. Its action mechanism to adjust HIF1‑VEGF‑Notch signaling pathway， induction of cerebral tissue angiogenesis， increase MVD， restore blood oxygen supply， and repair neuronal damage.

R285.5

江西省一流学科江西中医药大学中西医结合（zxyylxk20220103）；江西省中医药管理局科技计划项目（2020B0331）；江西省教育厅科学技术研究项目（GJJ211211）