Forni Monica, Mazzola Silvia, Ribeiro Luciana A, Pirrone Federica, Zannoni Augusta, Bernardini Chiara, Bacci Maria Laura, Albertini Mariangela
Department of Veterinary Morphophysiology and Animal Production, University of Bologna, Italy.
Regul Pept. 2005 Nov;131(1-3):89-96. doi: 10.1016/j.regpep.2005.07.001.
Endothelin (ET)-1 is a potent vasoconstrictive peptide and it is involved in the pathogenesis of septic shock. Blockade of ET-1 receptors abolishes the LPS-induced pulmonary hypertension and worsens the LPS-dependent systemic hypotension, but the role of ET-1 in sepsis remains uncertain. To determine the role of ET-1 in cardiovascular and respiratory derangement in a porcine model of endotoxemic shock we evaluated ET-1 plasma levels and ET-1 mRNA and protein levels in lung, liver, and heart as well as Endothelin Converting Enzyme-1, ET(A) and ET(B) receptors mRNA in the same tissues. Twelve piglets were randomised to sham operated or to LPS-treated (40 microg/kg/h for 4 h) groups. During the experiment, respiratory and circulatory parameters have been recorded and blood samples collected. At the end of the experiment the animals were sacrificed and tissue samples collected for real-time quantitative PCR and ELISA test. LPS infusion evokes a large increase in ET-1 plasma concentration, and in tissues mRNA levels, associated with an increase in pulmonary arterial pressure, as well as in pulmonary and systemic vascular resistances, and a decrease in stroke volume. LPS infusion caused also a derangement of respiratory mechanics, evidenced by an increase in resistance and a decrease in compliance of the respiratory system. ET(A) and ET(B) receptor mRNA levels were markedly decreased in liver and lung and slightly increased in heart, evidencing that ET receptor subtypes were differentially regulated in the major organs of endotoxin treated pigs. In conclusion our data show the presence of a continuative and differentially regulated stimulating mechanism of ET-1 expression during pig endotoxaemia as well as a fundamental role of ET-1 system in the cardiovascular and respiratory derangement.
内皮素（ET）-1是一种强效血管收缩肽，参与脓毒性休克的发病机制。阻断ET-1受体可消除脂多糖（LPS）诱导的肺动脉高压，并加重LPS依赖性全身低血压，但ET-1在脓毒症中的作用仍不明确。为了确定ET-1在猪内毒素血症休克模型中心血管和呼吸紊乱中的作用，我们评估了血浆ET-1水平以及肺、肝和心脏中ET-1 mRNA和蛋白水平，以及同一组织中的内皮素转换酶-1、ET（A）和ET（B）受体mRNA水平。12只仔猪被随机分为假手术组或LPS治疗组（40μg/kg/h，持续4小时）。实验过程中，记录呼吸和循环参数并采集血样。实验结束时，处死动物并采集组织样本进行实时定量PCR和ELISA检测。输注LPS可使ET-1血浆浓度大幅升高，组织mRNA水平也升高，同时伴有肺动脉压升高以及肺和全身血管阻力增加，而每搏输出量减少。输注LPS还导致呼吸力学紊乱，表现为呼吸系统阻力增加和顺应性降低。肝和肺中ET（A）和ET（B）受体mRNA水平显著降低，心脏中略有升高，表明内毒素处理猪的主要器官中ET受体亚型受到不同调节。总之，我们的数据表明，猪内毒素血症期间存在持续且差异调节的ET-1表达刺激机制，以及ET-1系统在心血管和呼吸紊乱中的重要作用。
