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一氧化氮在铁诱导的大鼠心肌损伤中的作用

陈莹莹, 夏强, 曹春梅, 叶治国, 沈岳良, 王琳琳

浙江大学医学院生理教研室,杭州(310031)

摘要

采用Langendorff灌流大鼠心脏和酶解分离的心肌细胞为实验模型，研究铁负荷下心肌损伤情况以及一氧化氮（NO）在铁诱导的心肌损伤中的地位。结果显示：（1）心肌铁负荷（Fe-HQ）可使分离心肌细胞张期细胞长度缩短、收缩幅度和速度降低，离体灌流心脏左室发展压（LVDP）、±dp/dt_(max)、冠脉流量呈现双相变化；冠脉流出液中乳酸脱氢酶（LDH）、肌酸激酶（CK）释放量和心肌丙二醛（MDA）增高。（2）NO的前体L－精氨酸（L－arginine, L-Arg）引起心肌细胞舒张期细胞长度缩短、收缩幅度降低。离体灌流心脏LVDP、冠脉流量、和±dp/dt_(max)增高，用K－H液复灌后可恢复正常。（3）L－Arg预处理，再行Fe-HQ灌流与单纯的L-Arg或Fe-HQ组相比，心肌细液中LDH、CK增加。（4）N_ω－硝基－L－精氨酸甲酯（L－NAME）和Fe-HQ合并灌流后，与单纯Fe-HQ组相比，心肌细胞舒张期细胞长度、收缩幅度和速度增加。L－NAME可阴断Fe-HQ引起的LVDP、左室舒张末压（LVEDP）和±dp/dt_(max)降低，冠脉流出液中LDH、CK增高。（5）用Triton X-100短暂处理以去除冠脉内皮后，与保留冠脉内皮的心肌相比，Fe-HQ引起的LVDP和±dp/dt_(max)的一过性增高现象被抑制，但对复灌期LVDP和±dp/dt_(max)的改变无明显影响。上述实验结果表明，L－Arg可加重铁诱导的心肌损伤作用；L－NAME可通过抑制NOS减轻铁引起的心肌损伤，其中冠脉内皮参与了铁的早期心肌作用。

关键词： 铁; 心脏; 一氧化氮; L-精氨酸; Nω-硝基-L-精氨酸甲酯

Role of nitric oxide in iron-induced toxicity in rat hearts

Chen Yingying, Xia Qiang, Cao Chunmei, Ye Zhiguo, Shen Yueliang, Wang Linlin

Department of Physiology, Zhejiang University School of Medicine,Hangzhou(310031)

Abstract

The aim of the present study was to explore the effect of nitric oxide (NO) on iron-induced toxicity in rat hearts. Langendorff perfused rat heart and enzymatically isolated cardiomyocytes were used. It was shown that lipophilic Fe-HQ reduced the contractile amplitude, velocity and end-diastolic cell length in the cardiomyocyte, while the left ventricular developed pressure (LVDP), ±dp/dt_(max), heart rate and coronary flow showed biphasic alterations, which increased in the first 2 min and then was followed by a decline in isolated perfused rat heart; the contents of lactate dehydrogenase (LDH) and creatine kinase (CK) in the coronary effluent and the malondialdehyde (MDA) in the myocardium were increased. L-arginine (L-Arg), an NO precursor, reduced the contractile amplitude and end-diastolic cell length in the cardiomyocyte; but reversibly increased LVDP, ±dp/dt_(max), and coronary flow in isolated perfused rat heart. Pretreatment with L-Arg aggravated the Fe-HQ-induced decrease in contractile amplitude, velocity and end-diastolic cell length in the cardiomyocyte; LVDP, ±dp/dt_(max), heart rate and coronary flow were significantly reduced in the perfused heart, and the levels of LDH and CK increased in the coronary effluent. In contrast, the NOS inhibitor N_ω-nitro-L-arginine methyl ester (L-NAME) blocked the Fe-HQ induced change in contractile amplitude, velocity and end-diastolic cell length in the cardiomyocyte; it inhibited the decrease in LVDP, LVEDP and ±dp/dt_(max), and reduced the LDH and CK. Removing endothelial cells in coronary vessels attenuated the increase in LVDP and ±dp/dt_(max) at the beginning of Fe-HQ perfusion. It is suggested that L-Arg aggravates the iron-induced cardiac dysfunction, No can mediate the iron-induced toxicity in heart, and endothelial cells in coronary vessels play an important role in the early stage of the effect of iron.

Key words: Iron;Heart;Nitric oxide;L-Arginine;NG-nitroarginine methyl ester

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引用本文：

陈莹莹, 夏强, 曹春梅, 叶治国, 沈岳良, 王琳琳. 一氧化氮在铁诱导的大鼠心肌损伤中的作用[J]. 生理学报 2002; 54 (4): .

Chen Yingying, Xia Qiang, Cao Chunmei, Ye Zhiguo, Shen Yueliang, Wang Linlin. Role of nitric oxide in iron-induced toxicity in rat hearts. Acta Physiol Sin 2002; 54 (4): (in Chinese with English abstract).