乌司他丁通过诱导miR-155抑制体外循环心脏手术患者炎症反应的作用机制研究
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篇名: 乌司他丁通过诱导miR-155抑制体外循环心脏手术患者炎症反应的作用机制研究
TITLE:
摘要: 目的:研究乌司他丁在体外循环(CPB)心脏手术中对患者炎症因子抑制作用的机制。方法:选取2012年7月-2016年7月于我院择期行CPB心脏手术的40例患者为研究对象,按照随机数字表法分为对照组和观察组,各20例。观察组患者于麻醉诱导后即给予30万U乌司他丁静脉泵注,以2.5 mL/min的速率在20 min内完成,再将70万U乌司他丁以0.2 mL/min的速率使用微量泵持续静脉泵注至术毕;对照组患者给予等容量生理盐水。分别于麻醉诱导前(术前)和CPB停止(术后)6、12、24 h采集患者血液标本,以实时定量逆转录聚合酶链反应和蛋白质免疫印迹法检测外周血单核细胞中微小核糖核酸155(miR-155)及其靶基因髓样分化因子88(MyD88)的表达情况;以酶联免疫吸附测定法检测血清肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)和IL-8的表达情况;采用Pearson相关系数分析观察组患者术后24 h的miR-155与TNF-α、IL-6、IL-8表达的相关性。结果:与对照组比较,观察组患者的miR-155表达水平显著升高,其靶基因MyD88的表达水平显著降低,炎症因子TNF-α、IL-6、IL-8的表达水平显著降低,差异均有统计学意义(P<0.01)。观察组患者术后24 h的miR-155与TNF-α、IL-6、IL-8的表达水平呈显著负相关(P<0.01)。结论:乌司他丁可通过诱导miR-155的表达来抑制炎症因子TNF-α、IL-6、IL-8的释放,这可能是该药在CPB心脏手术中发挥抗炎作用的新机制。
ABSTRACT: OBJECTIVE: To study the mechianism of inhibitory effect of ulinastain on inflammatory factors of patients during cardiopulmonary bypass (CPB) cardiac surgery. METHODS: Totally 40 patients underwent selective CPB cardiac surgery collected from our hospital during Jul. 2012-Jul. 2016 were divided into control group and observation group according to random number table, with 20 cases in each group. Observation group was given 300 000 U of ulinastatin at 2.5 mL/min by intravenous pump within 20 min after anesthesia induction,  then given 700 000 U of ulinastatin at 0.2 mL/min by continuous intravenous pump until operation finish. Control group was given equal volume of normal saline. Blood samples of patients were collected before anesthesia induction (before surgery) and 6, 12, 24 h after CPB (after surgery), respectively. The expression of miR-155 and its target gene MyD88 in peripheral blood mononuclear cells of each group were detected by Real-time PCR and Western blot. The expression of TNF-α, IL-6 and IL-8 were measured by ELISA. The correlation of miR-155 with the expression of TNF-α, IL-6 and IL-8 in patients of observation group 24 h after surgery were analyzed by using Pearson correlation analysis. RESULTS: Compared with control group, the expression of miR-155 in observation group was significantly increased, while the expression of its target gene MyD88 was significantly decreased; the expression of TNF-α, IL-6 and IL-8 were reduced significantly, with statistical significance (P<0.01). The expression of miR-155 was significantly negative correlation with the expression of TNF-α, IL-6 and IL-8 in the patients of observation group 24 h after surgery (P<0.01). CONCLUSIONS:Ulinastatin can inhibit the release of inflammatory factors TNF-α,IL-6 and IL-8 by inducing the expression of miR-155, which may be a new mechanism for the anti-inflammatory effect of the drug in CPB cardiac surgery.
期刊: 2017年第28卷第20期
作者: 徐黎青,韦江启
AUTHORS: XU Liqing,WEI Jiangqi
关键字: 乌司他丁;体外循环;心脏手术;微小核糖核酸155;炎症反应
KEYWORDS: Ulinastain; Cardiopulmonary bypass; Cardiac surgery; miR-155; Inflammatory reaction
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