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水飞蓟宾对大鼠心肌缺血再灌注损伤的保护作用及其机制。

Cardioprotective effects of the aqueous extract of Echinops cephalotes on myocardial ischemia-reperfusion in rats by modulation of MMP-2, MMP-9, TIMP, and oxidative stress.

机构信息

Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Biomed Pharmacother. 2024 Jul;176:116927. doi: 10.1016/j.biopha.2024.116927. Epub 2024 Jun 12.

Abstract

Echinops plants have received great attention for the treatment of many diseases due to pharmacological properties such as their antidiabetic, antioxidant, and anti-inflammatory characteristics. The major purpose of the present study was to investigate the cardioprotective benefits of Echinops cephalotes (Ech) against myocardial ischemia-reperfusion (MI/R) injury. Male Wistar rats were randomly allocated to three groups: sham, MI, and MI + Ech. The left coronary artery (LAD) was blocked for 30 minutes to induce MI. In the treatment group, rats were given 150 mg/kg/day of Ech extract for 28 days. Aqueous extracts were made from Echinops plants. To study heart function, fibrosis, cardiac damage indicators, and oxidative stress factors, echocardiography, Masson's trichrome staining, and biochemical tests were used. The expression of matrix metalloproteinase 2 and 9 (MMP2 and MMP-9) and tissue inhibitor of metalloproteinase (TIMP) was determined using Western blotting. Tissue damage was assessed using hematoxylin and eosin staining. MI group exhibited significantly reduced ejection fraction (EF) and fractional shortening (FS), enhanced levels of lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), cardiac Troponin I (cTnI), and malondialdehyde (MDA), as well as a decrease in the Glutathione (GSH) tissue content, reduced activity of superoxide dismutase (SOD), increasing fibrosis, upregulations of MMP-2 and MMP-9, and reduction of TIMP compared to the sham group. The findings suggest that Ech in particular, could be a promising therapeutic agent to reduce the damage in MI by targeting oxidative stress and modulating the activities of matrix metalloproteinases and their tissue inhibitors.

摘要

由于具有降血糖、抗氧化和抗炎等药理学特性,蓝刺头属植物在治疗许多疾病方面受到了广泛关注。本研究的主要目的是研究蓝刺头(Ech)对心肌缺血再灌注(MI/R)损伤的心脏保护作用。雄性 Wistar 大鼠随机分为三组:假手术组、MI 组和 MI+Ech 组。通过阻断左冠状动脉(LAD) 30 分钟来诱导 MI。在治疗组中,大鼠给予 150mg/kg/天的 Ech 提取物 28 天。从蓝刺头植物中提取水提取物。通过超声心动图、Masson 三色染色和生化试验研究心脏功能、纤维化、心脏损伤标志物和氧化应激因子。使用 Western blot 测定基质金属蛋白酶 2 和 9(MMP2 和 MMP-9)和组织金属蛋白酶抑制剂(TIMP)的表达。使用苏木精和伊红染色评估组织损伤。MI 组的射血分数(EF)和短轴缩短率(FS)明显降低,乳酸脱氢酶(LDH)、肌酸激酶 MB(CK-MB)、心肌肌钙蛋白 I(cTnI)和丙二醛(MDA)水平升高,谷胱甘肽(GSH)组织含量降低,超氧化物歧化酶(SOD)活性降低,纤维化增加,MMP-2 和 MMP-9 上调,TIMP 减少,与假手术组相比。这些发现表明,Ech 特别是可以通过靶向氧化应激和调节基质金属蛋白酶及其组织抑制剂的活性,成为一种有前途的治疗药物,以减少 MI 造成的损伤。

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