异槲皮苷对AngⅡ高血压小鼠血管重塑的作用及机制研究

doi:10.19586/j.2095-2341.2025.0044

生物技术进展 ›› 2025, Vol. 15 ›› Issue (5): 895-903.DOI: 10.19586/j.2095-2341.2025.0044

异槲皮苷对AngⅡ高血压小鼠血管重塑的作用及机制研究

李慧¹(), 张彦海², 拓步雄¹, 徐杰¹

^1.空军第九八六医院心血管内科，西安 710054
^2.空军第九八六医院老年医学科，西安 710054

收稿日期:2025-03-31 接受日期:2025-05-26 出版日期:2025-09-25 发布日期:2025-11-11
作者简介:李慧 E-mail: lit-mouse@163.com
基金资助:
陕西省科技攻关项目(2021JM-230)

Effect and Mechanism of Isoquercitrin on Vascular Remodeling in Ang Ⅱ Hypertensive Mice

Hui LI¹(), Yanhai ZHANG², Buxiong TUO¹, Jie XU¹

^1.Department of Cardiovascular Medicine，986th Hospital of Air Force，Xi'an 710054，China
^2.Department of Geriatrics，986th Hospital of Air Force，Xi'an 710054，China

Received:2025-03-31 Accepted:2025-05-26 Online:2025-09-25 Published:2025-11-11

摘要/Abstract

摘要：

研究旨在探究异槲皮苷（isoquercitrin，ISO）在血管紧张素Ⅱ（angiotensinⅡ，AngⅡ）诱导的高血压小鼠血管重塑中的作用及相关机制。通过微渗透泵连续28 d注入AngⅡ构建高血压小鼠模型，在模型构建过程的后14 d腹腔注射异槲皮苷，构建异槲皮苷小鼠模型。对照组给予同体积的生理盐水，检测造模过程中小鼠的血压变化。异槲皮苷处理14 d后，检测血清一氧化氮（nitric oxide，NO）和活性氧（reactive oxygen species，ROS）水平。收集血管组织，进行HE染色和Masson染色观察小鼠血管组织形态和纤维化情况。采用10 μmol·L^-1异槲皮苷预处理人脐静脉内皮细胞（human umbilical vein endothelial cells，HUVECs）6 h后，使用1 μmol·L^-1 AngⅡ干预12 h，对照组给予同剂量PBS处理。进行细胞计数试剂盒（cell counting kit-8，CCK-8）实验检测细胞活力，使用试剂盒检测ROS水平，末端标记法（terminal-deoxynucleoitidyl transferase mediated nick end labeling，TUNEL）染色检测细胞凋亡，qPCR检测细胞炎性因子水平，免疫荧光检测内皮细胞线粒体分裂，JC-1染色检测线粒体膜电位，Fluo-4 AM探针检测线粒体Ca²⁺含量。结果发现，与对照组相比，模型组小鼠血压和ROS水平升高，血清NO含量降低，血管壁增厚并发生纤维化。异槲皮苷组显著降低了高血压小鼠的血压和血清水平，恢复了NO含量，改善了血管壁增厚和血管纤维化。体外实验结果显示，异槲皮苷组显著降低了AngⅡ诱导的细胞ROS水平、细胞凋亡和炎性因子水平，缓解了线粒体过度分裂，改善了内皮细胞线粒体膜电位，并使Ca²⁺含量升高。结果表明，异槲皮苷通过减轻内皮细胞线粒体损伤，改善AngⅡ诱导的高血压小鼠血管重塑，进而达到降低血压的效果。

关键词: 高血压, 血管重塑, 异槲皮苷, AngⅡ, 内皮细胞, 线粒体损伤

Abstract:

The study aimed to investigate the role and related mechanisms of isoquercitrin （ISO） in vascular remodeling of hypertensive mice induced by AngⅡ. The hypertensive mouse model was constructed by continuous infusion of AngⅡ with mini-osmotic pump for 28 days. In the last 14 days of the process of AngⅡ model construction， the mouse model of isoquercitrin was constructed by intraperitoneal injection of isoquercitrin. The mice in control group were given the same volume of normal saline and the changes in blood pressure of the mice was measured during the molding process. After 14 days of isoquercetin treatment， mouse serum levels of NO and ROS in serum were detected. Collected vascular tissue and vascular morphology and fibrosis were observed by HE and Masson staining. In vitro， human umbilical vein endothelial cells （HUVECs） were pretreated with 10 μmol·L^-1 isoquercitrin for 6 h， followed by intervention with 1 μmol·L^-1 Ang Ⅱ for 12 h， and the control group was given the same dose of PBS. The activity of HUVECs was detected by cell counting kit-8 （CCK-8）. The level of ROS was detected by the kit. Apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling （TUNEL） staining. The levels of cell inflammatory factors were detected by qPCR. Mitochondrial division of endothelial cells was detected by immunofluorescence. Mitochondrial membrane potential was detected by JC-1 staining. Mitochondrial Ca²⁺ content was detected by Fluo-4 AM probe. The results showed that compared with controls， AngⅡ mice had increased blood pressure and ROS levels， decreased serum NO content， thickened blood vessel walls and fibrosis. Isoquercitrin treatment significantly reduced blood pressure and serum ROS， restored NO levels， and ameliorated vessel wall thickening and vascular fibrosis in AngⅡ mice. In vitro experimental results showed that isoquercitrin treatment reduced AngⅡ-induced cellular ROS levels， apoptosis， and attenuated inflammatory factor levels， alleviated excessive mitochondrial division， and ameliorated AngⅡ-induced elevation of mitochondrial membrane potential and Ca²⁺ content in HUVECs. The result showed that isoquercitrin ameliorates AngⅡ-induced vascular remodeling in hypertensive mice by attenuating mitochondrial damage in endothelial cells， leading to a reduction in blood pressure.

Key words: hypertension, vascular remodeling, isoquercitrin, AngⅡ, endothelial cell, mitochondrial damage

中图分类号:

Q946.83

李慧, 张彦海, 拓步雄, 徐杰. 异槲皮苷对AngⅡ高血压小鼠血管重塑的作用及机制研究[J]. 生物技术进展, 2025, 15(5): 895-903.

Hui LI, Yanhai ZHANG, Buxiong TUO, Jie XU. Effect and Mechanism of Isoquercitrin on Vascular Remodeling in Ang Ⅱ Hypertensive Mice[J]. Current Biotechnology, 2025, 15(5): 895-903.

图/表 7

图1 异槲皮苷对模型组小鼠收缩压、舒张压、血管NO和ROS水平的影响A~B：AngⅡ诱导小鼠高血压模型前及诱导后的收缩压和舒张压变化；C：血清中NO含量；D：血清中ROS含量。*表示差异在P<0.05水平上具有统计学意义。

Fig. 1 Effects of isoquercitrin on systolic blood pressure, diastolic blood pressure, NO and ROS in blood vessels in AngⅡ hypertensive mice

图2 异槲皮苷对AngⅡ小鼠血管组织形态和纤维化的影响A：HE染色及Masson染色检测小鼠血管组织形态及纤维化情况；B：血管壁厚度；C：胶原容积分数；*表示差异在P<0.05水平上具有统计学意义。

Fig. 2 Effects of isoquercitrin on vascular morphology and fibrosis in AngⅡ mice

图3 异槲皮苷对人脐静脉内皮细胞活性的影响

Fig. 3 Effect of isoquercitrin on activity of HUVECs

图4 异槲皮苷对HUVECs形态和功能的影响A：AngⅡ及异槲皮苷处理对HUVECs形态变化的影响；B：NO含量；C~D：ROS含量变化；E~F：TUNEL染色检测HUVECs凋亡情况；绿色表示凋亡细胞，蓝色表示细胞核；G~I： HUVECs细胞炎症因子IL-1β、IL-6、TNF-α的mRNA水平；*表示差异在P<0.05水平上具有统计学意义。

Fig. 4 Effect of isoquercitrin on morphology and function of HUVECs

图5 异槲皮苷对HUVECs线粒体功能的影响A：免疫荧光检测HUVECs线粒体分裂情况；绿色标记DRP1，蓝色标记细胞核；B：DRP1荧光强度定量分析；*表示差异在P<0.05水平上具有统计学意义。

Fig. 5 Effect of isoquercitrin on mitochondrial fission of HUVECs

图6 异槲皮苷对HUVECs线粒体膜电位的影响A：HUVECs线粒体膜电位；红色表示JC-1聚合物，绿色表示JC-1单体；B：JC-1单体荧光强度定量分析；*表示差异在P<0.05水平上具有统计学意义。

Fig. 6 Effect of isoquercitrin on mitochondrial membrane potential of HUVECs

图7 异槲皮苷对HUVECs Ca2+含量的影响A: Ca2+含量检测； B: Ca2+荧光强度的定量分析； *表示差异在P<0.05水平上具有统计学意义。

Fig. 7 Effect of isoquercitrin on the content of Ca2+ in HUVECs

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异槲皮苷对AngⅡ高血压小鼠血管重塑的作用及机制研究

Effect and Mechanism of Isoquercitrin on Vascular Remodeling in Ang Ⅱ Hypertensive Mice

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