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药物诱导预处理或远程缺血预处理对心脏保护中内在血管细胞外RNA/核糖核酸酶系统的影响。

Influence of Medication-Induced Preconditioning or Remote Ischemic Preconditioning on the Intrinsic Vascular Extracellular RNA/Ribonuclease System in Cardioprotection.

作者信息

Tolkmitt Konstantin J, Simsekyilmaz Sakine, Schipke Julia, Mühlfeld Christian, Preissner Klaus T, Böning Andreas

机构信息

Department of Cardiovascular Surgery, Medical School, Justus-Liebig-University, Giessen, Germany.

Institute of Pharmacology and Clinical Pharmacology, Universitatsklinikum Dusseldorf, Dusseldorf, Germany.

出版信息

Thorac Cardiovasc Surg. 2019 Sep;67(6):494-501. doi: 10.1055/s-0038-1675398. Epub 2018 Nov 16.

Abstract

BACKGROUND

It has been demonstrated that remote ischemic preconditioning (RIPC) increases ribonuclease (RNase) levels and protects the heart by reducing extracellular ribonucleic acid (eRNA). As medication-induced preconditioning (MIPC) is also a powerful tool for cardioprotection, we examined the influence of both types of preconditioning on the eRNA/RNase system.

METHODS

In 17 male rats, RIPC (3 × 5 minute hind-leg ischemia) or MIPC (isoflurane and buprenorphine anesthesia) was performed. Five rats served as control and did not undergo preconditioning (non-MIPC). After preconditioning, eRNA levels and RNase activity were determined in plasma, and the hearts were mounted on a blood-perfused Langendorff ischemia/reperfusion apparatus. Hemodynamic, metabolic, and electron microscopic parameters were determined. Furthermore, MIPC with one anesthetic drug only (isoflurane, buprenorphine, or etomidate) was induced in another five rats. After 30 minutes, eRNA levels and RNase activity were determined and compared with an RIPC group ( = 5).

RESULTS

The plasma of RIPC-treated rats had higher RNase activity and lower eRNA levels than that of MIPC-treated rats. In addition, RIPC increased RNase activity more than MIPC with one drug alone. The RNase activity and eRNA levels in these MIPC groups differed considerably. Hemodynamic parameters of RIPC- and MIPC-treated hearts were better preserved after 90-minute ischemia than those of non-MIPC hearts. No obvious differences were noted between MIPC and RIPC regarding hemodynamics, metabolism, or structural parameters.

CONCLUSIONS

Our results suggest that RIPC does not have any additional cardioprotective benefit in this experimental system. However, the influence of RIPC on the eRNA/RNase system was greater than that of MIPC.

摘要

背景

已有研究表明,远程缺血预处理(RIPC)可提高核糖核酸酶(RNase)水平,并通过减少细胞外核糖核酸(eRNA)来保护心脏。由于药物诱导预处理(MIPC)也是一种强大的心脏保护工具,我们研究了这两种预处理对eRNA/RNase系统的影响。

方法

对17只雄性大鼠进行RIPC(3次×5分钟后肢缺血)或MIPC(异氟烷和丁丙诺啡麻醉)。5只大鼠作为对照,未进行预处理(非MIPC)。预处理后,测定血浆中的eRNA水平和RNase活性,并将心脏安装在血液灌注的Langendorff缺血/再灌注装置上。测定血流动力学、代谢和电子显微镜参数。此外,在另外5只大鼠中仅用一种麻醉药物诱导MIPC(异氟烷、丁丙诺啡或依托咪酯)。30分钟后,测定eRNA水平和RNase活性,并与RIPC组(n = 5)进行比较。

结果

与MIPC处理的大鼠相比,RIPC处理的大鼠血浆具有更高的RNase活性和更低的eRNA水平。此外,RIPC比单独使用一种药物的MIPC更能提高RNase活性。这些MIPC组中的RNase活性和eRNA水平差异很大。缺血90分钟后,RIPC和MIPC处理的心脏的血流动力学参数比非MIPC心脏保存得更好。在血流动力学、代谢或结构参数方面,MIPC和RIPC之间未观察到明显差异。

结论

我们的结果表明,在该实验系统中,RIPC没有任何额外的心脏保护益处。然而,RIPC对eRNA/RNase系统的影响大于MIPC。

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