中药新药与临床药理2025，Vol.36Issue(6)：869-878,10.DOI:10.19378/j.issn.1003-9783.2025.06.004
桑术益肾降浊方调控内皮祖细胞改善去势高脂血症大鼠颈动脉损伤的作用及机制
Effect and Mechanism of Sangshu Yishen Jiangzhuo Formula in Regulating Endothelial Progenitor Cells to Improve Carotid Artery Injury in Castrated Hyperlipidemic Rats
摘要
Abstract
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.关键词
桑术益肾降浊方/血管内皮祖细胞/去势/高脂血症/颈动脉损伤/动脉粥样硬化/大鼠Key words
Sangshu Yishen Jiangzhuo Formula/endothelial progenitor cells/castration/hyperlipidemia/carotid artery injury/atherosclerosis/rats分类
医药卫生引用本文复制引用
朱倩华,王丹纳,刘建,杨洪艳,罗甜裕,聂广宁..桑术益肾降浊方调控内皮祖细胞改善去势高脂血症大鼠颈动脉损伤的作用及机制[J].中药新药与临床药理,2025,36(6):869-878,10.基金项目
广东省自然科学基金项目(2022A1515011651) （2022A1515011651）
省部共建中医湿证国家重点实验室(SZ2022ZZ47) （SZ2022ZZ47）
广东省中医院拔尖专项(BJ2022KY09) （BJ2022KY09）
广东省中医院优秀中医临床人才研修项目[(2024)88号]. （2024）
