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牛膝总皂苷提取物对自发性高血压大鼠血管内皮功能损伤的改善作用及机制研究
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| 篇名： | 牛膝总皂苷提取物对自发性高血压大鼠血管内皮功能损伤的改善作用及机制研究 |
| TITLE： | Improvement effects and mechanism of Achyranthes bidentata total saponins extract on vascular endothelial dysfunction in spontaneously hypertensive rats |
| 摘要： | 目的 基于细胞色素P4504A（CYP4A）/20-羟-二十烷四烯酸（/20-HETE）/G蛋白偶联受体75（GPR75）轴探究牛膝总皂苷（ABS）提取物对自发性高血压大鼠（SHR）血管内皮功能损伤的改善作用及机制。方法将10只Wistar-Kyoto大鼠设为正常对照组；将40只SHR根据收缩压进行分层后，按随机数字表法分为模型组（MOD组）、卡托普利阳性对照组（CAP组，10mg/kg）和ABS提取物低、高剂量组（ABS-L、ABS-H组，60、120mg/kg），每组10只。各组动物灌胃相应药物或等体积纯水，每天1次，连续28d。末次给药后，测量大鼠收缩压，检测血清中血管活性物质、炎症因子和氧化应激指标水平，观察大鼠胸主动脉病理形态学变化，检测胸主动脉组织中活性氧（ROS）水平及内皮型一氧化氮合酶（eNOS）、CYP4A、GPR75、核因子-κBp65（NF-κBp65）、磷酸化NF-κBp65、p22phox、还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶4（NOX4）的表达。结果给药28d后，与MOD组比较，ABS-L、ABS-H组大鼠收缩压及血清中20-HETE、血管紧张素Ⅱ、内皮素1、白细胞介素1β、白细胞介素6、肿瘤坏死因子α、细胞间黏附分子1和丙二醛水平均显著降低（P＜0.05或P＜0.01）；一氧化氮、超氧化物歧化酶、谷胱甘肽过氧化物酶和过氧化氢酶水平均显著升高（P＜0.05或P＜0.01）；胸主动脉内膜损伤减轻，内皮细胞形态改善；胸主动脉中ROS、CYP4A、GPR75、p22phox和NOX4的表达及NF-κBp65蛋白的磷酸化水平均显著下调/降低（P＜0.05或P＜0.01），eNOS的表达均显著上调（P＜0.05或P＜0.01）。结论ABS提取物可能通过下调CYP4A表达，减少20-HETE生成，抑制GPR75激活，进而抑制下游NF-κB和NOX4的活化，有效减轻SHR的炎症反应和氧化应激，从而改善其高血压相关血管内皮功能损伤。 |
| ABSTRACT： | OBJECTIVE To investigate the improvement effects and mechanism of Achyranthes bidentata total saponins （ABS） extract on vascular endothelial dysfunction in spontaneously hypertensive rat （SHR） based on cytochrome P450 4A （CYP4A）/20-hydroxyeicosatetetraenoic acid （20-HETE）/G protein-coupled receptor 75 （GPR75） axis. METHODS Ten Wistar- Kyoto rats were taken as the normal control group. Forty SHR were first stratified by systolic blood pressure and then， within each stratum， randomly assigned using a random-number table to the model group （MOD group）， captopril positive control group （CAP group， 10 mg/kg）， ABS low- and high-dose extract groups （ABS-L group， ABS-H group， 60 and 120 mg/kg）， with 10 rats in each group. Animals in each group were given the corresponding drug or equal volume of pure water by gavage， once a day， for 28 consecutive days. After the last administration， systolic blood pressure of rats was measured. The levels of vasoactive substances， inflammatory factors and oxidative stress indicators in serum were measured. The pathological changes of rat thoracic aorta were observed. The level of reactive oxygen species （ROS） in aortic tissue was analyzed. The expressions of endothelial nitric oxide synthase （eNOS）， CYP4A， GPR75， nuclear factor-κB p65 （NF-κB p65）， phosphorylated NF-κB p65， p22phox， and reduced nicotinamide adenine dinucleotide phosphate oxidase 4（NOX4） in thoracic aorta tissue were detected. RESULTS After 28 d of treatment， compared with MOD group， the systolic blood pressure of rats in the ABS-L and ABS-H groups decreased significantly. The levels of 20-HETE， angiotensin Ⅱ， interleukin-1β， interleukin-6， tumor necrosis factor-α， intercellular cell adhesion molecule-1 and malondialdehyde in serum were significantly reduced （P＜0.05 or P＜0.01）， while the levels of nitric oxide， superoxide dismutase， glutathione peroxidase and catalase were significantly increased （P＜0.05 or P＜0.01）. Intimal damage of thoracic aorta was reduced， and endothelial cell morphology was improved. The expressions of ROS， CYP4A， GPR75， p22phox， NOX4 and the phosphorylation level of NF-κB p65 protein in thoracic aorta were down-regulated or reduced （P＜0.05 or P＜0.01）， while the expression of eNOS was up-regulated （P＜0.05 or P＜0.01）. CONCLUSIONS ABS extract may alleviate the inflammatory response and oxidative stress in SHR effectively by down-regulating the expression of CYP4A， reducing the production of 20-HETE， inhibiting the activation of GPR75， and subsequently suppressing the activation of downstream NF-κB and NOX4， thereby improving hypertension-related vascular endothelial dysfunction. |
| 期刊： | 2026年第37卷第03期 |
| 作者： | 梁瑞峰；葛文静；寇晓波；田萍；安鸿志；魏征；张明利 |
| AUTHORS： | LIANG Ruifeng，GE Wenjing，KOU Xiaobo，TIAN Ping，AN Hongzhi，WEI Zheng，ZHANG Mingli |
| 关键字： | 牛膝总皂苷提取物；高血压；血管内皮功能损伤；20-羟-二十烷四烯酸；细胞色素P450 4A |
| KEYWORDS： | Achyranthes bidentata total saponins extract； hypertension； vascular endothelial dysfunction； 20-hydroxyeicosate- |
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