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高阿司匹林反应性血小板与 2 型糖尿病或原发性高胆固醇血症患者超氧化物歧化酶活性降低的相关性。

Association between High On-Aspirin Platelet Reactivity and Reduced Superoxide Dismutase Activity in Patients Affected by Type 2 Diabetes Mellitus or Primary Hypercholesterolemia.

机构信息

Department of Clinical and Biological Sciences of Turin University, 10043 Orbassano, Turin, Italy.

Metabolic Disease and Diabetes Unit, San Luigi Gonzaga Hospital, 10043 Orbassano, Turin, Italy.

出版信息

Int J Mol Sci. 2020 Jul 15;21(14):4983. doi: 10.3390/ijms21144983.

Abstract

Platelet hyperactivation is involved in the established prothrombotic condition of metabolic diseases such as Type 2 Diabetes Mellitus (T2DM) and familial hypercholesterolemia (HC), justifying the therapy with aspirin, a suppressor of thromboxane synthesis through the irreversible inhibition of cyclooxygenase-1 (COX-1), to prevent cardiovascular diseases. However, some patients on aspirin show a higher than expected platelet reactivity due, at least in part, to a pro-oxidant milieu. The aim of this study was to investigate platelet reactivity in T2DM ( = 103) or HC ( = 61) patients (aspirin, 100 mg/day) and its correlation with biomarkers of redox function including the superoxide anion scavenger superoxide dismutase (SOD) and the in vivo marker of oxidative stress urinary 8-iso-prostaglandin F. As results, in T2DM and HC subjects the prevalence of high on-aspirin platelet reactivity was comparable when both non-COX-1-dependent and COX-1-dependent assays were performed, and platelet reactivity is associated with a lower SOD activity that in a stepwise linear regression appears as the only predictor of platelet reactivity. To conclude, in T2DM and HC, similarly, the impairment of redox equilibrium associated with a decrease of SOD activity could contribute to a suboptimal response to aspirin.

摘要

血小板过度激活与 2 型糖尿病(T2DM)和家族性高胆固醇血症(HC)等代谢疾病的既定血栓形成状态有关,这使得通过不可逆抑制环氧化酶-1(COX-1)来抑制血栓素合成的阿司匹林成为预防心血管疾病的一种治疗方法。然而,一些服用阿司匹林的患者表现出高于预期的血小板反应性,至少部分原因是由于促氧化剂环境。本研究旨在调查 T2DM(=103)或 HC(=61)患者(阿司匹林,100mg/天)的血小板反应性及其与氧化还原功能生物标志物的相关性,包括超氧阴离子清除剂超氧化物歧化酶(SOD)和体内氧化应激标志物 8-异前列腺素 F。结果显示,在 T2DM 和 HC 患者中,当同时进行非 COX-1 依赖性和 COX-1 依赖性检测时,高阿司匹林反应性血小板的发生率相当,并且血小板反应性与 SOD 活性降低相关,在逐步线性回归中,SOD 活性是血小板反应性的唯一预测因子。总之,在 T2DM 和 HC 中,同样地,与 SOD 活性降低相关的氧化还原平衡失调可能导致阿司匹林反应不佳。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71e7/7404318/b1c931e6b799/ijms-21-04983-g001.jpg

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