Zaedi Sohel, Jesmin Subrina, Maeda Seiji, Shimojo Nobutake, Yamaguchi Iwao, Goto Katsutoshi, Miyauchi Takashi
Department of Cardiovascular Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Exp Biol Med (Maywood). 2006 Jun;231(6):992-6.
Septic shock is characterized by hypotension and a hyporeactive response to vasopressor agents. The pathogenesis is due to vascular leaks and an increased synthesis of cytokines and nitric oxide (NO). The present study examined the time-dependent alterations of endothelin-1 (ET-1) and the expression of NO synthase (NOS) in lung tissue in a septic rat model. Normal Sprague-Dawley (SD) rats aged 10 weeks received 15 mg/kg lipopolysaccharide (LPS) and then were sacrificed at different time points (1, 3, 6, and 10 hrs). Rats that did not receive LPS were considered to be controls. Both systolic and diastolic pressure decreased in SD rats after LPS administration. Time-dependent onset of features of acute lung injury, such as the infiltration of inflammatory cells and thickening of alveolar septa, were seen in rats that received LPS. A 2.8-fold increase in the expression of preproET-1 level was observed in lung tissue 6 hrs after LPS administration. The expression of endothelial NOS (eNOS) was also altered in lung tissue in a time-dependent fashion. After the administration of LPS, there was a 16-fold increase in the expression of eNOS mRNA. The peak expression of inducible NOS (iNOS) in lung tissue specimens obtained from rats that received LPS was 45-fold higher than that in control rats. ET-1 is a potent vasoconstrictor and thereby may play an important role in the pathogenesis of acute lung injury in a septic rat model. The increased expression of NOS may result in excess NO production and may also play a role in the pulmonary complications of endotoxemia.
脓毒性休克的特征为低血压以及对血管加压药反应性降低。其发病机制是由于血管渗漏以及细胞因子和一氧化氮（NO）合成增加。本研究在脓毒症大鼠模型中检测了肺组织中内皮素-1（ET-1）的时间依赖性变化以及一氧化氮合酶（NOS）的表达。10周龄的正常斯普拉格-道利（SD）大鼠接受15mg/kg脂多糖（LPS），然后在不同时间点（1、3、6和10小时）处死。未接受LPS的大鼠作为对照。给予LPS后，SD大鼠的收缩压和舒张压均降低。在接受LPS的大鼠中可见急性肺损伤特征的时间依赖性出现，如炎性细胞浸润和肺泡间隔增厚。给予LPS后6小时，肺组织中前体ET-1水平的表达增加了2.8倍。肺组织中内皮型NOS（eNOS）的表达也呈时间依赖性改变。给予LPS后，eNOS mRNA的表达增加了16倍。从接受LPS的大鼠获得的肺组织标本中诱导型NOS（iNOS）的峰值表达比对照大鼠高45倍。ET-1是一种强效血管收缩剂，因此可能在脓毒症大鼠模型急性肺损伤的发病机制中起重要作用。NOS表达增加可能导致NO产生过多，也可能在内毒素血症的肺部并发症中起作用。
