目的 基于血管内皮祖细胞（EPCs）探讨桑术益肾降浊方（SYJF）对去势高脂血症大鼠颈动脉损伤的作用 及机制。方法 将 50 只雌性 SD 大鼠随机分为 5 组：空白组、假手术组、模型组、中药组、西药组，每组各 10 只。采用去势+导丝损伤法+高脂饮食复制去势高脂血症颈动脉损伤大鼠模型。空白组、假手术组、模型组 予以等量生理盐水灌胃，中药组予以 SYJF 冻干粉生理盐水溶液（生药浓度 3.67 g·kg-1 ）灌胃，西药组予以戊酸 雌二醇生理盐水溶液（0.097 mg·kg-1 ）灌胃，每天 1 次，连续 8 周。采用 HE 染色法观察大鼠颈动脉内膜组织病 理变化，分别测量颈动脉管腔面积（LA）、内弹力板以内面积（IELA）、外弹力板以内面积（EELA），计算血管内 膜面积（IA）、中膜面积（MA）、颈动脉的内膜增生程度（DIH）、管腔狭窄程度（DLS）；Masson 染色法观察大鼠 颈动脉血管壁组织病理变化；分离、培养 EPCs，并通过细胞吞噬实验鉴定 EPCs；免疫荧光法检测 EPCs 表面 标记物 CD31、CD34、CD133、VEGFR-2 的表达水平；流式细胞术检测表达 CD31、CD34、CD133、VEGFR-2 的 EPCs 细胞比例；通过血管形成实验检测 EPCs 血管新生能力。结果 （1）与假手术组比较，模型组大鼠的血 管内膜增厚，血管平滑肌排列紊乱，内膜下有明显的脂质沉积和泡沫细胞聚集；大鼠颈动脉 LA 水平显著下降 （P＜0.01），IA、MA、DIH、DLS 水平显著升高（P＜0.05，P＜0.01）；颈动脉血管内皮不连续，部分区域内膜 脱落，脱落区域胶原纤维增多，凸向管腔，有形成纤维斑块的趋势，平滑肌排列紊乱，胶原容积分数显著上升 （P＜0.01）。与模型组比较，中药组及西药组大鼠的颈动脉血管内膜增厚现象趋于缓解，血管平滑肌排列更整 齐，内膜下也未见明显泡沫细胞聚集及脂质沉积；中药组及西药组大鼠颈动脉 LA 显著升高（P＜0.01），MA、 DIH、DLS 水平显著下降（P＜0.01）；颈动脉血管内皮更为完整连续，平滑肌排列整齐，胶原容积分数显著降 低（P＜0.01）。（2）鉴定结果显示 5 组细胞均为正在分化的大鼠 EPCs。与假手术组比较，模型组大鼠 EPCs 的 CD31、VEGFR-2 表达水平显著降低（P＜0.01），CD133 表达水平显著升高（P＜0.05）；表达 CD31、CD34、 VEGFR-2 的细胞比例均显著降低（P＜0.01），表达 CD133 的细胞比例显著升高（P＜0.01）；EPCs 新生的管腔数 目显著减少（P＜0.01）。与模型组比较，中药组及西药组大鼠 EPCs 的 CD31、VEGFR-2 表达水平显著升高 （P＜0.01），中药组 EPCs 的 CD133 表达水平明显降低（P＜0.05）；中药组及西药组 EPCs 中表达 CD31、CD34、 VEGFR-2 的细胞比例显著升高（P＜0.01），表达 CD133 的细胞比例显著降低（P＜0.01）；EPCs 新生的管腔数目 显著增多（P＜0.01）。结论 SYJF 可能通过促进 EPCs 增殖、分化及增强血管生成能力，抑制血管修复过程中 血管内膜过度增生、血管狭窄、血管胶原纤维变性，促进去势高脂血症大鼠颈动脉损伤修复，从而延缓动脉粥 样硬化进程，对绝经后心血管疾病的防治具有参考意义。

Objective To investigate the effect and mechanism of Sangshu Yishen Jiangzhuo Formula （SYJF） on carotid artery injury in castrated hyperlipidemic rats based on vascular endothelial progenitor cells （EPCs）. Methods Fifty SD rats were randomly divided into five groups：blank group，sham-operated group，model group，traditional Chinese medicine （TCM） group，and western medicine group，with 10 rats in each group. A rat model of carotid artery injury in castrated hyperlipidemic rats was established using castration + wire injury + high-fat diet. The blank group，sham-operated group，and model group were given an equal volume of saline by gavage. The TCM group was administered SYJF lyophilized powder saline solution （crude drug concentration：3.67 g·kg-1 ） by gavage，and the western medicine group was given estradiol valerate saline solution （0.097 mg · kg-1 ） by gavage， once daily for 8 consecutive weeks. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the carotid artery intima. The lumen area （LA），internal elastic lamina area （IELA），and external elastic lamina area （EELA） of the carotid artery were measured， and the intima area （IA）， media area （MA）， degree of intimal hyperplasia （DIH），and degree of lumen stenosis （DLS） were calculated. Masson staining was used to observe the histopathological changes in the carotid artery wall. EPCs were isolated， cultured， and identified through a phagocytosis assay. Immunofluorescence was used to detect the expression levels of EPC surface markers CD31，CD34， CD133， and VEGFR-2. Flow cytometry was used to measure the proportion of EPCs expressing CD31， CD34， CD133， and VEGFR-2. The angiogenic ability of EPCs was assessed using a vascular formation assay. Results （1） Compared with the sham-operated group， the model group showed thickened vascular intima， disordered arrangement of vascular smooth muscle，significant lipid deposition，and foam cell aggregation under the intima. The LA of the carotid artery in the model group was significantly decreased （P＜0.01），while IA，MA，DIH，and DLS were significantly increased （P＜0.05， P＜0.01）. The carotid artery endothelium was discontinuous， with partial intimal detachment，increased collagen fibers in the detached areas，protruding into the lumen，and a tendency to form fibrous plaques. The arrangement of smooth muscle was disordered， and the collagen volume fraction was significantly increased （P＜0.01） . Compared with the model group，the TCM and western medicine groups showed alleviated intimal thickening， more orderly arrangement of vascular smooth muscle， and no significant foam cell aggregation or lipid deposition under the intima. The LA of the carotid artery in the TCM and western medicine groups was significantly increased （P＜0.01），while MA，DIH，and DLS were significantly decreased （P＜0.01） . The carotid artery endothelium was more continuous，smooth muscle was orderly arranged，and the collagen volume fraction was significantly reduced （P＜0.01）. （2） Identification results showed that the cells in all five groups were differentiating rat EPCs. Compared with the sham-operated group， the expression levels of CD31 and VEGFR-2 in EPCs of the model group were significantly decreased （P＜0.01），while the expression level of CD133 was significantly increased （P＜0.05）. The proportions of cells expressing CD31，CD34，and VEGFR-2 were significantly decreased （P＜0.01）， while the proportion of cells expressing CD133 was significantly increased （P＜0.01）. The number of newly formed lumens by EPCs was significantly reduced （P＜0.01）. Compared with the model group，the expression levels of CD31 and VEGFR-2 in EPCs of the TCM and western medicine groups were significantly increased （P＜ 0.01），while the expression level of CD133 in the TCM group was significantly decreased （P＜0.05）. The proportions of EPCs expressing CD31，CD34，and VEGFR-2 in the TCM and western medicine groups were significantly increased （P＜0.01）， while the proportion of cells expressing CD133 was significantly decreased （P＜0.01）. The number of newly formed lumens by EPCs was significantly increased （P＜0.01）. Conclusion SYJF may promote the proliferation and differentiation of EPCs and enhance their angiogenic ability， thereby inhibiting excessive intimal hyperplasia， vascular stenosis，and collagen fiber degeneration during vascular repair. It promotes the repair of carotid artery injury in castrated hyperlipidemic rats，delaying the progression of atherosclerosis. This provides a reference for the prevention and treatment of postmenopausal cardiovascular diseases.

R285.5

广东省自然科学基金项目（2022A1515011651）；省部共建中医湿证国家重点实验室（SZ2022ZZ47）；广东省中医院拔尖专项（BJ2022KY09）； 广东省中医院优秀中医临床人才研修项目（[ 2024）88号]