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
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( 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。

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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
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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.

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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
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  • 在线发布日期: 2018-07-17