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血管紧张素转换酶I/D基因多态性对雷米普利在冠状动脉搭桥术患者炎症反应及心肌损伤中作用的影响

Role of ACE I/D gene polymorphisms on the effect of ramipril in inflammatory response and myocardial injury in patients undergoing coronary artery bypass grafts.

作者信息

Urhan Küçük Meral, Sucu Nehir, Şahan Firat Seyhan, Aytaçoğlu Barlas Naim, Vezir Özden, Bozali Caner, Canacankatan Necmiye, Kul Seval, Tunçtan Bahar

机构信息

Faculty of Medicine, Department of Medical Biology, Mustafa Kemal University, 31024, Antakya, Hatay, Turkey,

出版信息

Eur J Clin Pharmacol. 2014 Dec;70(12):1443-51. doi: 10.1007/s00228-014-1751-5. Epub 2014 Sep 27.

DOI:10.1007/s00228-014-1751-5
PMID:25256070
Abstract

BACKGROUND

Angiotensin-converting enzyme (ACE) inhibitors block angiotensin II formation and release bradykinin, which is effective in the regulation of oxidoinflammatory injury. Some reports denote alterations in the effectiveness of ACE inhibitors in association with ACE insertion/deletion (I/D) gene polymorphisms. This study investigates the effects of ramipril on the oxidoinflammatory cytokines (IL-6, IL-8, TNF-alpha) and TnT (myocardial injury marker) and their alteration in association with ACE I/D gene polymorphisms.

METHODS

The study group (n = 51) patients received ramipril before coronary artery bypass grafting (CABG), while patients not receiving ramipril (n = 51) constituted the controls. TNFα, IL-6, and IL-8 were evaluated using ELISA and TnT by electrochemiluminescence methods before the induction of anesthesia (t1), at the 20th minute following cross-clamping (t2), at the end of the operation (t3), and at the 24th hour from the commencement of anesthesia (t4). Genotyping was performed by PCR.

RESULTS

Differences between the groups were significant at t4 for the TNFα and at t3 for IL-6 (p < 0.05). The TnT levels increased from t2 onward in the control group and were highest in t3. Changes in t3 and t4 values in both groups according to their t1 values were significant (p < 0.05). However, differences between the groups were insignificant (p > 0.05). The IL-6, IL-8, TNFα, and TnT serum levels had no correlation with the ACE I/D gene polymorphism.

CONCLUSION

Low cytokine and TnT levels in the study group, especially after cross-clamping, may indicate the protective effect of ramipril from oxidoinflammatory injury. This effect did not appear to be associated with the ACE I/D gene polymorphism.

摘要

背景

血管紧张素转换酶(ACE)抑制剂可阻断血管紧张素II的形成并释放缓激肽,这对氧化应激性损伤的调节有效。一些报告指出,ACE抑制剂的有效性改变与ACE插入/缺失(I/D)基因多态性有关。本研究调查了雷米普利对氧化应激性细胞因子(IL-6、IL-8、TNF-α)和肌钙蛋白T(心肌损伤标志物)的影响,以及它们与ACE I/D基因多态性的关系。

方法

研究组(n = 51)患者在冠状动脉旁路移植术(CABG)前接受雷米普利治疗,未接受雷米普利治疗的患者(n = 51)作为对照组。在麻醉诱导前(t1)、交叉夹闭后第20分钟(t2)、手术结束时(t3)和麻醉开始后24小时(t4),采用酶联免疫吸附测定法(ELISA)评估TNFα、IL-6和IL-8,采用电化学发光法评估肌钙蛋白T。通过聚合酶链反应(PCR)进行基因分型。

结果

两组之间在t4时TNFα水平和t3时IL-6水平存在显著差异(p < 0.05)。对照组中肌钙蛋白T水平从t2开始升高,在t3时最高。两组t3和t4时的值相对于t1时的值均有显著变化(p < 0.05)。然而,两组之间的差异不显著(p > 0.05)。IL-6、IL-8、TNFα和肌钙蛋白T血清水平与ACE I/D基因多态性无相关性。

结论

研究组中细胞因子和肌钙蛋白T水平较低,尤其是在交叉夹闭后,可能表明雷米普利对氧化应激性损伤具有保护作用。这种作用似乎与ACE I/D基因多态性无关。

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