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内源性CO在大鼠离体心脏缺血再灌注中的保护作用

周振, 马爽, 刘杰, 纪巧荣, 曹成珠, 李晓娜, 汤锋, 张伟^*

青海大学高原医学研究中心；青海省高原医学应用基础重点实验室，西宁 810001

摘要

本文旨在观察研究内源性CO在大鼠离体心脏缺血再灌注中的作用。大鼠经内源性CO激动剂原卟啉氯化钴(CoPP)和内源性CO抑制剂锌原卟啉(ZnPP)处理后，采用Langendorff离体心脏灌流系统完成心脏缺血再灌注模型，停灌(缺血)时间设定为30 min，分别采集离体心脏稳定期和再灌注后30 min心功能指标参数，ELISA方法检测心肌组织cGMP含量，比色法测定血浆中内源性CO的含量以及再灌注10 min时灌流液中肌酸激酶(creatine kinase, CK)、乳酸脱氢酶(lactic dehydrogenase, LDH)等心肌酶的指标。结果显示，停灌前离体心脏跳动平稳，CoPP组、ZnPP组和对照组心脏各项功能指标均保持稳定，三组间心功能指标无明显差异；再灌注后，三组间心功能指标出现显著性差异(P < 0.05)，与停灌前相比，对照组和ZnPP组心功能均明显下降(P < 0.05)，且ZnPP组下降较为显著，而CoPP组仍能保持停灌前水平。与此同时，三组大鼠体内CO含量、离体心肌酶学指标和再灌注后恢复稳定时间也有明显的差异(P < 0.05)，和对照组相比，CoPP组复灌稳定恢复时间减少，灌流液中CK和LDH含量显著减少，血浆内源性CO含量和心肌cGMP含量显著增加，而ZnPP组则呈现截然相反的结果。以上结果提示，内源性CO可维持一定的心脏舒缩能力、缩短心脏复跳时间，在心脏缺血再灌注中起到了保护作用。

关键词： 内源性一氧化碳; 缺血再灌注损伤; Langendorff; 心脏功能; 肌酸激酶; 乳酸脱氢酶

分类号：R331.3；R392.7

Protective effects of endogenous carbon monoxide against myocardial ischemia- reperfusion injury in rats

ZHOU Zhen, MA Shuang, Liu Jie, JI Qiao-Rong, CAO Cheng-Zhu, LI Xiao-Na, TANG Feng, Zhang Wei^*

High Altitude Medical Research Center of Qinghai University; the Key Laboratory of High Altitude Medical Application of Qinghai Province, Xining 810001, China

Abstract

The present study is aimed to explore the effects of endogenous carbon monoxide on the ischemia-reperfusion in rats. Wistar rats were intraperitoneally injected with protoporphyrin cobalt chloride (CoPP, an endogenous carbon monoxide agonist, 5 mg/kg), zinc protoporphyrin (ZnPP, an endogenous carbon monoxide inhibitor, 5 mg/kg) or saline. Twenty-four hours after injection, the myocardial ischemia-reperfusion model was made by Langendorff isolated cardiac perfusion system, and cardiac function parameters were collected. Myocardial cGMP content was measured by ELISA, and the endogenous carbon monoxide in plasma and myocardial enzymes in perfusate at 10 min after reperfusion were measured by colorimetry. The results showed that before ischemia the cardiac functions of CoPP, ZnPP and control groups were stable, and there were no significant differences. After reperfusion, cardiac functions had significant differences among the three groups (P < 0.05). Compared with pre-ischemia, the cardiac function decreased and obvious cardiac arrest was shown in control and ZnPP groups, while the cardiac function in CoPP group did not change significantly, maintaining a relatively stable level. At the same time, three groups’ carbon monoxide level, myocardial enzymology and the cardiac function recovery time after reperfusion also had significant differences (P < 0.05). Compared with those in control group, recovery after reperfusion was faster, activities of creatine kinase and lactic dehydrogenase were significantly decreased, plasma CO and myocardial cGMP contents were significantly increased in CoPP group, while these changes were completely opposite in ZnPP group. It is concluded that endogenous carbon monoxide can maintain cardiac function, shorten the time of cardiac function recovery, and play a protective role in cardiac ischemia-reperfusion.

Key words: endogenous carbon monoxide; ischemia reperfusion injury; Langendorff; cardiac function; creatine kinase; lactic dehydrogenase

收稿日期：2017-09-08　　录用日期：2018-03-28

通讯作者：张伟　　E-mail: zw0228@sina.com

DOI: 10.13294/j.aps.2018.0027

引用本文：

周振, 马爽, 刘杰, 纪巧荣, 曹成珠, 李晓娜, 汤锋, 张伟. 内源性CO在大鼠离体心脏缺血再灌注中的保护作用[J]. 生理学报 2018; 70 (2): 115-122.

ZHOU Zhen, MA Shuang, Liu Jie, JI Qiao-Rong, CAO Cheng-Zhu, LI Xiao-Na, TANG Feng, Zhang Wei. Protective effects of endogenous carbon monoxide against myocardial ischemia- reperfusion injury in rats. Acta Physiol Sin 2018; 70 (2): 115-122 (in Chinese with English abstract).