赤芍总苷对高血压大鼠血管重构基质金属蛋白酶9、金属蛋白酶组织抑制因子1和血管壁氧化应激的干预作用
作者:
作者单位:

( 1.广东药科大学附属第一医院心内科,广东省广州市 510080;3.广东药科大学附属第一医院风湿科,广东省广州市 510080;2.中山大学附属第一医院病理科,广东省广州市 510080)

作者简介:

林忠伟,医学博士,副主任医师,主要从事高血压、冠心病研究,E-mail为gdpcxn3110@163.com。

基金项目:

广东省中医药局科研课题(20142086);广东省自然科学基金项目(2015A030313583)


Effect of total paeony glycoside on matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1 and oxidative stress of vascular remodeling in hypertensive rats
Author:
Affiliation:

1.Department of Cardiology, ;3.Department of Rheumatology, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, China;2.Department of Pathology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China)

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    摘要:

    目的 探讨赤芍总苷(TPG)对自发性高血压大鼠(SHR)血管重构基质金属蛋白酶9(MMP-9)、金属蛋白酶组织抑制因子1(TIMP-1)和血管壁氧化应激的干预作用。 方法 30只8周龄雄性SHR大鼠随机分为3组:低剂量TPG组(低剂量组,n=10)、高剂量TPG组(高剂量组,n=10)、对照组(n=10);另外以Wistar大鼠作为空白组(n=8)。低剂量组、高剂量组分别以100、200 mg/(kg·d)的TPG灌胃,对照组、空白组以2 mL生理盐水灌胃。8周后,酶联免疫吸附测定法测定血清MMP-9、TIMP-1水平;活性氧(ROS)荧光探针检测胸主动脉壁细胞氧化应激水平;免疫组织化学染色检测主动脉MMP-9、TIMP-1蛋白表达。 结果 与空白组比较,对照组MMP-9、TIMP-1血清水平及血管壁MMP-9、TIMP-1蛋白表达均明显升高(P<0.05)。TPG治疗后,MMP-9有所下降,高剂量组与对照组比较,差异有统计学意义(P<0.05);但TIMP-1在低剂量组、高剂量组、对照组间差异无统计学意义(P>0.05)。对照组胸主动脉ROS水平明显高于空白组,而低剂量组、高剂量组ROS水平较对照组下降。 结论 高血压血管重构存在血管氧化应激和MMP-9水平升高;TPG能够抑制动脉氧化应激和MMP-9水平,改善高血压血管重构,可作为高血压治疗的辅助药物。

    Abstract:

    Aim To investigate the intervention effect of total paeony glycoside (TPG) on matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and oxidative stress of vascular remodeling in spontaneously hypertensive rats (SHR). Methods 30 male 8 weeks-old SHR rats were randomly divided into 3 groups:low-dose TPG group (low-dose group, n=10), high-dose TPG group (high-dose group, n=10) and control group (n=10); In addition, Wistar rats were used as a blank group (n=8). Low-dose group and high-dose group had intragastric administration with 100 and 200 mg/(kg·d) TPG respectively, and control group and blank group had intragastric administration with 2 mL physiological saline. After 8 weeks, serum levels of MMP-9 and TIMP-1 were detected by enzyme-linked immunosorbent assay; Oxidative stress level of thoracic aorta wall cells was determined by reactive oxygen species (ROS) fluorescence probe; Expressions of MMP-9 and TIMP-1 protein in the aorta was detected by immunohistochemical staining. Results Compared with the blank group, the serum levels of MMP-9 and TIMP-1 and the expressions of MMP-9 and TIMP-1 protein in the vascular wall were significantly increased in the control group (P<0.05). After TPG treatment, MMP-9 was decreased, and the difference between high-dose group and control group was statistically significant (P<0.05); However, there was no significant difference in TIMP-1 among low-dose group, high-dose group and control group (P>0.05). The ROS level of thoracic aorta in control group was significantly higher than that in blank group, while the ROS level in low-dose group and high-dose group was lower than that of the control group. Conclusion There are the increases of vascular oxidative stress and MMP-9 level in hypertensive vascular remodeling. TPG can inhibit arterial oxidative stress and MMP-9 level and improve vascular remodeling in hypertension. It can be used as an auxiliary remedy for the treatment of hypertension.

    参考文献
    [1] 伍章保, 王汀, 刘青云, 等.赤芍总苷抗凝血作用机制研究.安徽中医学院学报, 7,6(3):39-42.
    [2] 肖文豪, 王卓, 李瑞莹, 等.赤芍总苷对自发性高血压大鼠血小板sCD4OL和炎症因子的干预作用.广东药学院学报, 6,2(4):481-484.
    [3] 张璐, 薛梅, 马晓娟, 等.赤芍川芎有效部位对兔动脉粥样硬化基质金属蛋白酶的影响.中国中西医结合杂志, 9,9(6):514-518.
    [4] Su J, Zhang P, Zhang JJ, et al.Effects of total glucosides of paeony on oxidative stress in the kidney from diabetic rats.Phytomedicine, 0,7(3-4):254-260.
    [5] Lin Z, Wang Z, Li G, et al.Fibulin-3 may improve vascular health through inhibition of MMP-2/9 and oxidative stress in spontaneously hypertensive rats.Mol Med Rep, 6,3(5):3805-3812.
    [6] 徐红梅, 刘清云, 戴敏, 等.赤芍总苷对大鼠血小板功能的影响.合肥工业大学学报(自然科学版), 3,6(1):141-144.
    [7] Dhingra R, Pencina MJ, Schrader P, et al.Relations of matrix remodeling biomarkers to blood pressure progression and incidence of hypertension in the community.Circulation, 9,9(8):1101-1107.
    [8] Cave AC, Brewer AC, Narayanapanicker A, et al.NADPH oxidases in cardiovascular health and disease.Antioxid Redox Signal, 6,8(5-6):691-728.
    [9] 陈瑗, 周玫.氧化应激-炎症在动脉粥样硬化发生发展中作用研究的新进展.中国动脉硬化杂志, 8,6(10):757-762.
    [10] Jahandideh F, Majumder K, Chakrabarti S, et al.Beneficial effects of simulated gastro-intestinal digests of fried egg and its fractions on blood pressure, plasma lipids and oxidative stress in spontaneously hypertensive rats.PLoS One, 4,9(12):e115006.
    [11] Schulz E, Gori T, Münzel T.Oxidative stress and endothelial dysfunction in hypertension.Hypertens Res, 1,4(6):665-673.
    [12] Tsutsui H, Kinugawa S, Matsushima S.Oxidative stress and heart failure.Am J Physiol Heart Circ Physiol, 1,1(6):H2181-H2190.
    [13] Bahrehmand F, Vaisi-Raygani A, Kiani A, et al.Matrix metalloproteinase 9 polymorphisms and systemic lupus erythematosus:correlation with systemic inflammatory markers and oxidative stress.Lupus, 5,4(6):597-605.
    [14] 李慧颖, 李静.阿托伐他汀对高血压病早期肾损害患者MMP-9及TIMP-1的影响.中国动脉硬化杂志, 5,3(6):607-612.
    [15] 梁日欣, 黄璐琦, 刘菊福, 等.药对川芎和赤芍对高脂血症大鼠降脂、抗氧化及血管内皮功能的实验观察.中国实验方剂学杂志, 2,8(1):43-45.
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林忠伟,王卓,喻婵,张炽明,李稳磊,肖文豪.赤芍总苷对高血压大鼠血管重构基质金属蛋白酶9、金属蛋白酶组织抑制因子1和血管壁氧化应激的干预作用[J].中国动脉硬化杂志,2018,26(8):774~778.

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  • 收稿日期:2017-10-30
  • 最后修改日期:2017-12-06
  • 在线发布日期: 2018-07-17