血清SIRT1水平与射血分...关性分析及对预后的影响研究_夏海亭.pdf

现代生物医学进展Progress in Modern Biomedicine Vol.23NO.2JAN.2023doi:10.13241/ki.pmb.2023.02.029血清 SIRT1 水平与射血分数保留的心力衰竭患者炎性因子、氧化应激的相关性分析及对预后的影响研究*夏海亭1路长鸿2杨侃1孙庆楠3王恺4（1 青岛大学医学部 山东 青岛 266071；2 青岛阜外心血管病医院心内科 山东 青岛 266034；3 淄博市淄川区医院心内科 山东 淄博 255199；4 淄博市中心医院重症医学科 山东 淄博 255020）摘要 目的：探讨血清去乙酰化酶 1（SIRT1）水平与射血分数保留的心力衰竭（HFpEF）患者炎性因子、氧化应激的相关性，分析SIRT1 预测 HFpEF 患者预后的价值。方法：选择 2019 年 10 月至 2021 年 6 月青岛阜外心血管病医院收治的 190 例 HFpEF 患者为 HFpEF 组，92 例心功能正常的健康体检志愿者为对照组。HFpEF 患者出院后随访 12 个月，统计随访期间不良心血管事件发生情况，多因素 Logistic 回归分析 HFpEF 患者预后不良的影响因素。结果：HFpEF 组血清 SIRT1 水平低于对照组（P0.05），白细胞介素（IL）-6、肿瘤坏死因子-（TNF-）、C 反应蛋白（CRP）、丙二醛（MDA）、晚期氧化蛋白产物（AOPP）水平高于对照组（P0.05）。HFpEF 患者血清 SIRT1 水平与 IL-6、TNF-、CRP、MDA、AOPP 呈负相关（r=-0.496、-0.502、-0.419、-0.533、-0.542，P0.05）。190 例患者 2 例失访，余 188 例 HFpEF 患者中 41 例预后不良，147 例预后良好。预后不良组美国纽约心脏病协会（NYHA）级比例、IL-6、TNF-、CRP、MDA、AOPP、N 末端 B 型利钠肽前体（NT-proBNP）水平、左室收缩末期内径（LVEDS）、左室舒张末期内径（LVEDD）、二尖瓣舒张早期血流峰值（E）与舒张晚期血流峰值（A）（E/A）高于预后良好组（P0.05），血清 SIRT1 水平、左心室射血分数（LVEF）低于预后良好组（P0.05）。高 IL-6、高 MDA、高 NT-proBNP 是 HFpEF 患者预后不良的危险因素（P0.05），SIRT1 是 HFpEF 患者预后不良的保护因素（P0.05）。结论：HFpEF 患者血清 SIRT1 水平降低，与 HFpEF 患者炎症反应、氧化应激以及预后不良的发生有关，可作为 HFpEF 患者预后评估的辅助指标。关键词：去乙酰化酶 1；射血分数保留的心力衰竭；炎症因子；氧化应激；预后中图分类号：R541.61文献标识码：A文章编号：1673-6273（2023）02-356-05Correlation Analysis of Serum SIRT1 Level with Inflammatory Factors andOxidative Stress in Patients with Heart Failure with Preserved EjectionFraction and its Influence Study on Prognosis*XIA Hai-ting1,LU Chang-hong2,YANG Kan1,SUN Qing-nan3,WANG Kai4(1 Medical Department of Qingdao University,Qingdao,Shandong,266071,China;2 Department of Internal Medicine-Cardiovascular,Qingdao Fuwai Cardiovascular Hospital,Qingdao,Shandong,266034,China;3 Department of Internal Medicine-Cardiovascular,Zibo Zichuan District Hospital,Zibo,Shandong,255199,China;4 Department of Critical Care,Zibo Central Hospital,Zibo,Shandong,255020,China)ABSTRACT Objective:To investigate the correlation between serum Sirtuin 1(SIRT1)level and inflammatory factors and oxida-tive stress in patients with heart failure with preserved ejection fraction(HFpEF),and to analyze the prognostic value of SIRT1 in patientswith HFpEF.Methods:190 patients with HFpEF who were admitted to Qingdao Fuwai Cardiovascular Hospital from October 2019 toJune 2021 were selected as HFpEF group,and 92 healthy examination volunteers with normal cardiac function were selected as controlgroup.The patients with HFpEF were followed up for 12 months after discharge.The incidence of adverse cardiovascular events duringthe follow-up period was statistically analyzed.Multivariate Logistic regression analysis was used to analyze the influencing factors ofpoor prognosis in patients with HFpEF.Results:The serum SIRT1 level in the HFpEF group was lower than that in the control group(P0.05),and the interleukin(IL)-6,tumor necrosis factor-(TNF-),C-reactive protein(CRP),malondialdehyde(MDA)and advancedoxidation protein product(AOPP)levels were higher than those in control group(P0.05).Serum SIRT1 level in patients with HFpEFwere negatively correlated with IL-6,TNF-,CRP,MDA and AOPP(r=-0.496,-0.502,-0.419,-0.533,-0.542,P0.05).2 cases of the 190patients were lost to follow-up.Among the remaining 188 patients with HFpEF,41 had poor prognosis,and 147 had good prognosis.New York Heart Association(NYHA)grade ratio,IL-6,TNF-,CRP,MDA,AOPP,N-terminal pro-B-type natriuretic peptide*基金项目：山东省医药卫生科技发展计划项目（202010000131）作者简介：夏海亭（1983-），男，硕士研究生，主要从事心力衰竭方向的研究，E-mail:通讯作者：路长鸿（1979-），男，硕士，主任医师，主要从事心脏病的介入治疗和心脏康复方向的研究，E-mail:（收稿日期：2022-05-26 接受日期：2022-06-22）356现代生物医学进展Progress in Modern Biomedicine Vol.23NO.2JAN.2023(NT-proBNP)levels,left ventricular end-systolic diameter(LVEDS),left ventricular end-diastolic diameter(LVEDD),mitral valve earlydiastolic Peak Flow(E)and Late diastolic Peak Flow(A)(E/A)in the poor prognosis group were higher than those in the good prognosisgroup(P0.05),and the serum SIRT1 level and left ventricular ejection fraction(LVEF)were lower than those in the good prognosisgroup(P0.05).High IL-6,high MDA and high NT-proBNP were risk factors for poor prognosis in patients with HFpEF(P0.05),andSIRT1 was a protective factor for poor prognosis in patients with HFpEF(P0.05).Conclusion:The decrease serum SIRT1 level inpatients with HFpEF is related to the occurrence of inflammatory reaction,oxidative stress and poor prognosis in patients with HFpEF,which can be used as an auxiliary indicator for the prognosis evaluation of patients with HFpEF.Key words:SIRT1;Heart failure with preserved ejection fraction;Inflammatory factors;Oxidative stress;PrognosisChinese Library Classification(CLC):R541.61Document code:AArticle ID:1673-6273(2023)02-356-05前言射血分数保留的心力衰竭（HFpEF）是心力衰竭的主要类型，约占所有心力衰竭类型的一半，尽管 HFpEF 患者左心室射血分数（LVEF）可保留正常，但是其左心室结构、舒张功能已出现明显异常，是导致患者死亡的主要原因1,2。炎症反应和氧化应激在 HFpEF 发病机制中发挥关键作用，HFpEF 多伴肥胖、糖尿病、高血压等基础疾病，代谢负荷增加、血流动力学异常可激活促炎信号通路，并引起氧化应激反应，最终促使心肌纤维化、心脏结构和功能异常3,4。去乙酰化酶 1（SIRT1）是一种组蛋白去乙酰化酶，又叫沉默信息调节因子 1，属于组蛋白去乙酰化酶 III 家族成员，具有调节细胞代谢、基因转录、能量平衡作用5，SIRT1 可抑制丝裂原活化蛋白激酶和信号转导及转录激活子 3 氧化应激相关信号通路，减轻氧化应激6，还可通过抑制炎症反应的主要调节因子-转