脂多糖性休克大鼠血浆和主要器官中硫化氢含量的变化和意义

Changes of hydrogen sulfide content in plasma and tissues of rats with LPS-induced shock

目的:探讨内毒素休克(endotoxic shock,ES)大鼠血浆及肝、肾、心、肺、主动脉等主要器官组织中内源性硫化氢(hydrogen sulfide,H2S)的含量变化及意义。方法:用静脉注射脂多糖(lipopolysaccharide,LPS)法制备LPS攻击大鼠模型,将雄性Wistar大鼠随机分为正常对照组、LPS组、LPS+硫氢化钠(NaHS,H2S供体)组、LPS+炔丙基甘氨酸(PPG,H2S代谢酶抑制剂)组。观察给药后240 min内大鼠平均动脉压(mean arterial pressure,MAP)的变化及测定血浆和以上主要器官中H2S含量,并分析其相关性;光镜观察主要器官的形态学变化。结果:与正常对照组相比,LPS组大鼠血压迅速下降,血浆H2S含量于LPS注射后显著增高,肝、肾、心、肺和主动脉组织中H2S含量亦明显增高(均P<0.05),并出现组织结构损伤;给予PPG能显著抑制血浆以及各组织中H2S含量的增高,并可显著减轻LPS所致的血压下降(均P<0.05)和组织损伤;而给予H2S供体NaHS后,与LPS组相比,大鼠血浆以及各组织中H2S含量显著增高,血压明显下降(均P<0.05),组织损伤加重。LPS攻击大鼠血浆及组织中H2S含量与血压呈高度负相关(均P<0.05)。结论:H2S是一种新的内源性介质,可能参与了ES的一系列病理生理过程。

AIM： To investigate the changes and significance of hydrogen sulfide （H2S） in both plasma and various tissues, including liver, kidney, heart, lung and arteriae aorta, in rats with LPS - induced shock. METHODS ： A rat model of shock induced by injection of lipopolysaccharide （LPS） was developed. Male Wistar rats were divided into four groups： control group, LPS group, LPS ＋ NaHS （H2S donor） group and LPS ＋ propargylglycine （PPG, metabolic enzyme inhibitor of H2S） group. The mean arterial pressure （MAP） of rats within 240 min was observed,and H2S contents were determined. The structures of various tissues were observed. RESULTS： Administration of LPS to male Wistar rats caused a sustained fall in MAP, various tissue injuries and a significant increase in H2S contents in plasma as well as liver, kidney, heart, lung and arteriae aorta within 240 min（all P 〈0. 05）. Treatment with metabolic enzyme inhibitor of H2S, propargylglycine, was shown to reduce H2S content elevation in plasma as well as liver, kidney, heart, lung, and arteriae aorta, and ameliorate the hypotension and tissue injuries caused by LPS（ all P 〈 0. 05 ）. However, treatment with H2S donor -NaHs was shown to increase H2S content elevation in plasma as well as liver, kidney, heart, lung and arteriae aorta, and aggravate the hypotension and tissue injuries caused by LPS（ all P 〈0. 05 ）. Endogenous H2S contents in both plasma and various tissues were negatively correlated with MAP（ all P 〈 0. 05 ）. CONCLUSION： H2S may be a new endogenous mediator and play a role in the pathogenesis of endotoxic shock.