急性ST段抬高型心肌梗死患者早期应用PCSK9抑制剂对血清趋化素和白细胞介素37的影响

孟利民; 杨华; 信栓力; 常超; 赵秀峰; 刘吉祥; 李琴; 张仁杰

doi:10.12125/j.chj.202009029

急性ST段抬高型心肌梗死患者早期应用PCSK9抑制剂对血清趋化素和白细胞介素37的影响

Effect of early application of PCSK9 inhibitor on serum chemerin and interleukin-37 levels in acute ST segment elevation myocardial infarction patients

摘要

摘要:
目的探讨急性ST段抬高型心肌梗死（STEMI）患者早期应用前蛋白转化酶枯草溶菌素9（PCSK9）抑制剂依洛尤单抗对血清趋化素（chemerin）、白细胞介素37（IL-37）水平的影响。
方法入选行急诊经皮冠状动脉介入（PCI）术的STEMI患者60例，之前均未服用他汀或其他降脂药物。急诊PCI术后按1:1的比例随机分配为试验组（30例）和对照组（30例），分别给予阿托伐他汀（40 mg/d）+依洛尤单抗（每2周140 mg皮下注射）和单独给予阿托伐他汀（40 mg/d），疗程为4周。检测治疗前后chemerin、IL-37和血脂水平，包括总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）及脂蛋白（a）LP(a)。记录患者不良反应发生情况。
结果治疗后，两组患者的chemerin水平明显下降，IL-37水平明显升高，且试验组变化的更明显chemerin：（114±18）ng/ml 比（125±15）ng/ml，IL-37：（63±6）ng/L 比（58±6）ng/L，P<0.05。血脂方面，两组患者的TC和LDL-C水平较治疗前明显降低，且试验组下降的更明显TC：（3.6±1.3）mmol/L 比（4.6±1.3）mmol/L，LDL-C：（1.8±0.9）mmol/L 比（2.6±0.8）mmol/L，P<0.05。试验组的LP(a)水平较治疗前明显降低（242±94）mg/L 比（314±100）mg/L，P<0.05。TG和HDL-C水平较治疗前差异无统计学意义。两组均无肝功能异常、肌酶增高等不良反应。
结论依洛尤单抗可降低chemerin水平，升高IL-37水平，在快速有效降脂的同时发挥抗炎作用，且具有一定的安全性，为STEMI患者早期应用PCSK9抑制剂提供依据。

Abstract:
AIM To investigate the effect of early application of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab on serum chemerin and interleukin-37(IL-37) levels in patients with acute ST segment elevation myocardial infarction (STEMI).
METHODS Sixty STEMI patients were randomly divided into experimental group (n=30) and control group (n=30) after emergency PCI. These patients had not been treated with statins and other types of lipid-lowering agents. The patients in the experimental group were injected subcutaneously with evolocumab every 2 weeks at a dose 140 mg and in combination with atorvastatin (40 mg/d), while the patients in the control group were treated atorvastatin (40 mg/d) alone for 4 weeks. The levels of chemerin, IL-37 and serum lipid profile were measured before and 4 weeks after treatment, including total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and lipoprotein (a)LP(a). Adverse events were recorded.
RESULTS After 4 weeks of treatment, the level of chemerin was significantly lower and that of IL-37 was higher in the two groups than those before treatment, but the changes were more obvious in the experiment group chemerin:(114±18) ng/ml vs. (125±15) ng/ml, IL-37:(63±6) ng/L vs. (58±6) ng/L, P<0.05. After 4 weeks of treatment, the levels of TC and LDL-C in the two groups were significantly lower than those before treatment, while the changes were more obvious in the experiment group TC:(3.6±1.3) mmol/L vs. (4.6±1.3) mmol/L, LDL-C:(1.8±0.9) mmol/L vs. (2.6±0.8) mmol/L, P<0.05. The level of LP(a) in the experiment group was significantly lower than that before treatment (242±94) mg/L vs. (314±100) mg/L, P<0.05. The levels of TG and HDL-C in the two groups were not statistically significant. No other adverse reactions such as abnormal liver functions and increased myocardial enzyme occurred in the two groups.
CONCLUSION In STEMI patients following revascularization, evolocumab effectively reduces the serum chemerin level and increases the serum IL-37 level, and while rapidly reducing the lipid, it plays an anti-inflammatory role. It is safe to some extent.

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