硫化氢与内毒素血症大鼠心肌损伤的关系

为探讨硫化氢（hydrogen sulfide,H2S）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,H2S代谢酶抑制剂）组、LPS＋NaHS（H2S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-α（tumor necrosis factor-α,TNF-α）和H2S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-α、H2S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-α、H2S含量显著增高,且血浆中H2S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P〈0．05）;心肌组织TNF-α、H2S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-α、H2S含量的增高,并可显著减轻LPS所致的血压下降（均P〈0．05）和心肌组织损伤,降低心肌组织中TNF-α、H2S含量及LDH、MPO活性;（3）给予NaHS后,与LPS组相比,大鼠血浆TNF-α、H2S含量增高,血压明显下降（均P〈0．05）,心肌组织损伤加重,心肌组织中TNF-α、H2S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H2S生成增多。

Relationship between hydrogen sulfide and myocardial damage in endotoxemic rats

To investigate the changes and role of hydrogen sulfide (H2S) 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 H2S) group and LPS + NaHS (H2S donor) group. The mean arterial pressure (MAP) of rats within 4 h was observed, TNF-alpha and H2S contents in plasma, TNF-alpha and H2S 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 H2S contents in plasma (P<0.05). Plasmic H2S 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 H2S contents, LDH and MPO activity in cardiac muscles and myocardial damage. Treatment with PPG reduced the increases in TNF-alpha and H2S contents in plasma, TNF-alpha and H2S 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 H2S contents in plasma, TNF-alpha and H2S contents, LDH and MPO activity in cardiac muscles, and aggravated the hypotensive action and tissue injuries caused by LPS administration (P<0.05). It is suggested that hypotension and myocardial damage in endotoxemic rats are partly induced by increase in H2S content.