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别嘌醇对慢性心力衰竭患者左心室功能和基质金属蛋白酶(MMPs)活性的治疗作用。

Therapeutic effects of allopurinol on the function of left ventricular and activity of matrix metalloproteinase enzymes (MMPs) in patients with chronic heart failure.

机构信息

Department of Cardiovascular medicine, Chenzhou No.1 People's Hospital, Chenzhou City, China 423000.

Children Department of Ophthalmology, Chenzhou No.1 People's Hospital, Chenzhou City, China 423000.

出版信息

Cell Mol Biol (Noisy-le-grand). 2022 May 31;68(5):96-102. doi: 10.14715/cmb/2022.68.5.13.

Abstract

Heart failure is a growing public health problem, especially in the elderly, often occurring due to ischemia and coronary artery disease. Allopurinol can protect against myocardial ischemia and improve myocardial energy utilization during ischemia. On the other hand, matrix metalloproteinase (MMP) enzymes play an essential role in causing atherosclerosis, obstruction, and myocardial infarction. Therefore, in the present study, the effect of allopurinol on the function of the left ventricular and the activity of MMP-1, MMP-2, MMP-3, and MMP-9 were evaluated in heart failure patients. In this clinical trial, 82 patients were randomly assigned to allopurinol or placebo in addition to standard treatment. Echocardiographic evaluations were performed before treatment and six months after treatment. Also, after allopurinol treatment, plasma and peripheral blood mononuclear cells were extracted from control and intervention groups. The active form of MMPs was measured by ELISA and mRNA expression by Real-time PCR. The rate of change in left ventricular ejection fraction in the allopurinol group was significantly higher than patients in the control group. There was also found more improvement in NYHA class in patients receiving allopurinol than in the control group. ELISA results showed that all plasma MMP levels in the control group were significantly higher than those in the allopurinol group (P<0.001). Quantitative determination of mRNA expression in MMPs by Real-time RT-PCR revealed that, except for MMP-9, there was no significant difference in the expression of evaluated MMPs between the treatment and control groups. In general, the results showed that long-term administration of allopurinol improves left ventricular function, and it has beneficial effects on the life quality of patients with heart failure.

摘要

心力衰竭是一个日益严重的公共卫生问题,尤其是在老年人中,常因缺血和冠状动脉疾病而发生。别嘌醇可预防心肌缺血,并在缺血期间改善心肌能量利用。另一方面,基质金属蛋白酶(MMP)酶在导致动脉粥样硬化、阻塞和心肌梗死方面发挥着重要作用。因此,在本研究中,评估了别嘌醇对心力衰竭患者左心室功能和 MMP-1、MMP-2、MMP-3 和 MMP-9 活性的影响。在这项临床试验中,82 名患者被随机分配到别嘌醇或安慰剂加标准治疗组。在治疗前和治疗后 6 个月进行超声心动图评估。此外,在别嘌醇治疗后,从对照组和干预组中提取血浆和外周血单核细胞。通过 ELISA 测量 MMP 的活性形式,通过实时 PCR 测量 mRNA 表达。别嘌醇组左心室射血分数的变化率明显高于对照组。接受别嘌醇治疗的患者 NYHA 分级也有改善。ELISA 结果显示,对照组所有血浆 MMP 水平均明显高于别嘌醇组(P<0.001)。通过实时 RT-PCR 定量测定 MMPs 的 mRNA 表达显示,除 MMP-9 外,治疗组和对照组之间评估的 MMPs 表达无显著差异。总的来说,结果表明,长期服用别嘌醇可改善左心室功能,并对心力衰竭患者的生活质量产生有益影响。

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