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静脉内急性输注免疫球蛋白通过抑制半胱天冬酶-3预防心肌缺血-再灌注损伤。

Acute Intravenous Infusion of Immunoglobulins Protects Against Myocardial Ischemia-Reperfusion Injury Through Inhibition of Caspase-3.

作者信息

Al-Herz Waleed, Babiker Fawzi

机构信息

Department of Pediatric and, Kuwait City, Kuwait.

Allergy and Clinical Immunology Unit, Department of Pediatric, Al-Sabah Hospital, Kuwait City, Kuwait.

出版信息

Cell Physiol Biochem. 2017;42(6):2295-2306. doi: 10.1159/000480002. Epub 2017 Aug 17.

DOI:10.1159/000480002
PMID:28848148
Abstract

BACKGROUND/AIMS: To investigate the cardioprotective effects of intravenous immunoglobulins (IVIG) in rats subjected to regional myocardial ischemia reperfusion (I/R).

METHODS

Langendorff-perfused rat hearts were used in this study. Hearts subjected to regional ischemia served as a negative untreated control. The effects of IVIG pre- and post-ischemic treatment on left ventricular function, coronary vascular dynamics and contractility were assessed. IVIG were administered in either a low or high dose. The infarct size was determined using triphenyltetrazolium chloride and through biochemical assays using the measured creatine kinase and lactate dehydrogenase levels. Apoptosis was evaluated by the TUNEL assay, and the caspase-3 expression level was assessed by immunoblotting. The cytokine levels were measured by ELISA.

RESULTS

Low and high doses of immunoglobulins administered 2 hours before sacrifice, before the ischemic insult or at reperfusion resulted in a significant improvement in cardiac hemodynamics, coronary vascular dynamics and heart contractility. A significant decrease in the infarct size and cardiac enzymes was also evident compared to those in the control. IVIG administered as an infusion at reperfusion or pre-treatment resulted in a marked decrease in myocyte apoptosis, which was associated with decreased levels of caspase-3 expression in the supernatants of homogenized left ventricles. Infusion of IVIG both pre-ischemia and at reperfusion did not show the same protective effects.

CONCLUSIONS

This study demonstrates a novel protection to the heart by low and high doses of IVIG given either pre- or post-ischemia.

摘要

背景/目的:研究静脉注射免疫球蛋白(IVIG)对局部心肌缺血再灌注(I/R)大鼠的心脏保护作用。

方法

本研究采用Langendorff灌注大鼠心脏。局部缺血的心脏作为未处理的阴性对照。评估缺血前后IVIG治疗对左心室功能、冠状动脉血管动力学和收缩性的影响。IVIG采用低剂量或高剂量给药。使用氯化三苯基四氮唑测定梗死面积,并通过测量肌酸激酶和乳酸脱氢酶水平进行生化分析。通过TUNEL法评估细胞凋亡,并通过免疫印迹法评估半胱天冬酶-3的表达水平。通过ELISA测定细胞因子水平。

结果

在处死前2小时、缺血损伤前或再灌注时给予低剂量和高剂量的免疫球蛋白,可显著改善心脏血流动力学、冠状动脉血管动力学和心脏收缩性。与对照组相比,梗死面积和心肌酶也显著降低。在再灌注时或预处理时静脉输注IVIG可显著减少心肌细胞凋亡,这与左心室匀浆上清液中半胱天冬酶-3表达水平降低有关。缺血前和再灌注时均输注IVIG未显示相同的保护作用。

结论

本研究表明,缺血前后给予低剂量和高剂量的IVIG对心脏具有新的保护作用。

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