Pintér Örs, Hardi Péter, Nagy Tibor, Gasz Balázs, Kovács Viktoria, Arató Endre, Sínay László, Lénárd László, Jancsó Gábor
Heart Institute, Medical School, University of Pécs, Pécs, Hungary.
Department of Surgical Research and Techniques, Medical School, University of Pécs, Pécs, Hungary.
Clin Hemorheol Microcirc. 2017;66(3):261-272. doi: 10.3233/CH-170270.
Patients having coronary artery disease treated by coronary bypass or PCI procedure are exposed to tissue damage because of the phenomenon called reperfusion injury. Reperfusion injury can be characterized/monitored by oxidative stress parameters, inflammatory markers and by post-operative complication rate.
Beyond the obvious factors determining its severity (affected myocardial mass, ischaemic time, collateral circulation etc.) we examined the GST enzyme group's most cardio selective member, GSTP1 and its genetic polymorphism if there is any genetically determined preventive effect on the above-mentioned parameters.
We have performed randomized prospective study in the Heart Institute of Pecs with 862 patients, treated by coronary bypass or PCI procedure. Blood samples were taken a day before, one hour, one day, one week after the operation. Leucocyte count (WBC), myeloperoxidase (MPO), thiol group (SH); Superoxide dismutase (SOD), malondialdehyde (MDA), reduced Glutathione (GSH) level was checked in different periods of time as a comparison. The onset of myocardial damage and the corresponding necro enzyme level changes were registered in the perioperative period. Our patient's GSTP1 allele pair combinations (A, B, or C) were determined by real time PCR method.
In patients with GSTP1 AA genotype we have found significance level reaching plasma concentration rise in SOD and MDA, and drop in GSH, SH. The CKMB concentration rise in the post-operative 24 hours was significantly higher in the GSTP1 AA group.
According to our results the AA allele combination can be considered as a risk factor. GSTP1-AA allele pair has negative effect on ischemia-reperfusion tolerance of the heart. In case of cardiovascular interventions, the study of GST enzyme polymorphisms can be an independent risk stratification factor in determining the perioperative risk in the future.
接受冠状动脉搭桥术或经皮冠状动脉介入治疗(PCI)的冠心病患者会因再灌注损伤现象而遭受组织损伤。再灌注损伤可通过氧化应激参数、炎症标志物和术后并发症发生率来表征/监测。
除了决定其严重程度的明显因素(受影响的心肌质量、缺血时间、侧支循环等)外,我们研究了谷胱甘肽S-转移酶(GST)酶组中最具心脏选择性的成员GSTP1及其基因多态性,看是否对上述参数有任何基因决定的预防作用。
我们在佩奇心脏研究所对862例接受冠状动脉搭桥术或PCI治疗的患者进行了随机前瞻性研究。在手术前一天、术后1小时、1天、1周采集血样。在不同时间段检查白细胞计数(WBC)、髓过氧化物酶(MPO)、巯基(SH);超氧化物歧化酶(SOD)、丙二醛(MDA)、还原型谷胱甘肽(GSH)水平作为比较。记录围手术期心肌损伤的发生情况和相应坏死酶水平的变化。通过实时聚合酶链反应(PCR)方法确定我们患者的GSTP1等位基因对组合(A、B或C)。
在GSTP1 AA基因型患者中,我们发现SOD和MDA的血浆浓度升高以及GSH、SH降低具有显著意义。GSTP1 AA组术后24小时肌酸激酶同工酶(CKMB)浓度升高明显更高。
根据我们的结果,AA等位基因组合可被视为一个危险因素。GSTP1-AA等位基因对心脏缺血再灌注耐受性有负面影响。在心血管介入治疗中,研究GST酶多态性可能成为未来确定围手术期风险的一个独立风险分层因素。