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硫化氢与内毒素血症大鼠心肌损伤的关系

羡晓辉, 黄新莉, 周晓红, 张景琨, 凌亦凌

河北医科大学病理生理学教研室.河北,石家庄 050017

摘要

为探讨硫化氢（hydrogen sulfide，H_(2)S）与内毒素血症大鼠心肌损伤的关系，采用静脉注射脂多糖（lipopolysaccharide，LPS）的方法制备内毒素血症大鼠模型，将雄性Wistar大鼠随机分为正常对照组、LPS组、LPS+炔丙基甘氨酸（propargylglycine，PPG，H_(2)S代谢酶抑制剂）组、LPS+NaHS（H_(2)S供体）组。观察给药后4h内大鼠平均动脉压（mean arterial pressure，MAP）的变化，测定血浆肿瘤坏死因子--#alpha#（tumor necrosis factor--#alpha#，TNF--#alpha#）和H_(2)S含量，光学显微镜观察心肌组织形态学变化并测定心肌组织中TNF--#alpha#、H_(2)S含量及乳酸脱氢酶（lactate dehydrogenase，LDH）和髓过氧化物酶（myeloperoxidase，MPO）的活性。结果如下：（1）与正常对照组相比，LPS组大鼠血压迅速下降，血浆TNF--#alpha#、H_(2)S含量显著增高，且血浆中H_(2)S含量与血压呈显著负相关，LPS注射后1、2、4h时相关系数分别为--0.936、--0.913和--0.908（均{sl P}<0.05）；心肌组织TNF--#alpha#、H_(2)S含量及LDH、MPO活性也明显升高，并出现组织损伤；（2）给予PPG能显著抑制血浆TNF--#alpha#、H_(2)S含量的增高，并可显著减轻LPS所致的血压下降（均{sl P}<0.05）和心肌组织损伤，降低心肌组织中TNF--#alpha#、H_(2)S含量及LDH、MPO活性；（3）给予NaHS后，与LPS组相比，大鼠血浆TNF--#alpha#、H_(2)S含量增高，血压明显下降（均{sl P}<0.05），心肌组织损伤加重，心肌组织中TNF--#alpha#、H_(2)S含量及LDH、MPO活性增高。结果提示，内毒素血症大鼠低血压和心肌损伤的部分原因是由于H_(2)S生成增多。

关键词： 硫化氢; 内毒素; 心肌; 大鼠

Relationship between hydrogen sulfide and myocardial damage in endotoxemic rats

Xian Xiaohui, Huang Xinli, Zhou Xiaohong, Zhang Jingkun, Ling Yiling

Department of Pathophysiology, Hebei Medical University.Shijiazhuang 050017,Hebei

Abstract

To investigate the changes and role of hydrogen sulfide （H_(2)S） in myocardial damage in endotoxemic rats, a rat model of endotoxemia induced by injection of lipopolysaccharide （LPS） was developed. Male Wistar rats were divided into four groups： control group, LPS group, LPS + propargylglycine （PPG, a metabolic enzyme inhibitor of H_(2)S） group and LPS + NariS （H_(2)S donor） group. The mean arterial pressure （MAP） of rats within 4 h was observed, TNF-#alpha# and H_(2)S contents in plasma, TNF-#alpha# and H_(2)S contents, lactate dehydrogenase （LDH） and myeloperoxidase （MPO） activity in cardiac muscles were determined. The morphological structure of cardiac muscle was observed. Administration of LPS caused a sustained fall in MAP within 4 h, and significant increases in TNF-#alpha# and H_(2)S contents in plasma （P〈0.05）. Plasmic H_(2)S content was negatively correlated with MAP （r = -0.936, -0.913 and -0.908 at 1, 2 and 4 h, respectively, P〈0.05）. LPS also induced increases in TNF-#alpha# and H_(2)S contents, LDH and MPO activity in cardiac muscles and myocardial damage. Treatment with PPG reduced the increases in TNF-#alpha# and H_(2)S contents in plasma, TNF-#alpha# and H_(2)S contents, LDH and MPO activity in cardiac muscles, ameliorated the hypotensive effect and myocardial damage caused by LPS administration （P〈 0.05）. However, treatment with NaHS increased TNF-#alpha# and H_(2)S contents in plasma, TNF-#alpha# and H_(2)S contents, LDH and MPO activity in cardiac muscles, and aggravated the hypotensive action and tissue injuries caused by LPS administration （P〈0.05）. It issuggested that hypotension and myocardial damage in endotoxemic rats are partly induced by increase in H_(2)S content.

Key words: hydrogen sulfide;Endotoxin;Cardiac muscle;Rat

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引用本文：

羡晓辉, 黄新莉, 周晓红, 张景琨, 凌亦凌. 硫化氢与内毒素血症大鼠心肌损伤的关系[J]. 生理学报 2007; 59 (3): 357-362.

Xian Xiaohui, Huang Xinli, Zhou Xiaohong, Zhang Jingkun, Ling Yiling. Relationship between hydrogen sulfide and myocardial damage in endotoxemic rats. Acta Physiol Sin 2007; 59 (3): 357-362 (in Chinese with English abstract).