PDF(Pubmed)
Abstract：
Substance P (SP), encoded by the Tac1 gene, has been shown to promote leukocyte infiltration and organ impairment in mice with sepsis. Neurokinin-1 receptor (NK1R) is the major receptor that mediates the detrimental impact of SP on sepsis. This investigation studied whether SP affects the expression of adhesion molecules, including intercellular cell adhesion molecule-1 (ICAM1) and vascular cell adhesion molecule-1 (VCAM1) on vascular endothelial cells in the liver and lungs, contributing to leukocyte infiltration in these tissues of mice with sepsis. Sepsis was induced by caecal ligation and puncture (CLP) surgery in mice. The actions of SP were inhibited by deleting the Tac1 gene, blocking NK1R, or combining these two methods. The activity of myeloperoxidase and the concentrations of ICAM1 and VCAM1 in the liver and lungs, as well as the expression of ICAM1 and VCAM1 on vascular endothelial cells in these tissues, were measured. The activity of myeloperoxidase and the concentration of ICAM1 and VCAM1 in the liver and lungs, as well as the expression of ICAM1 and VCAM1 on vascular endothelial cells in these tissues, increased in mice with CLP surgery-induced sepsis. Suppressing the biosynthesis of SP and its interactions with NK1R attenuated CLP surgery-induced alterations in the liver and lungs of mice. Our findings indicate that SP upregulates the expression of ICAM1 and VCAM1 on vascular endothelial cells in the liver and lungs, thereby increasing leukocyte infiltration in these tissues of mice with CLP surgery-induced sepsis by activating NK1R.
摘要：
物质P(SP),由Tac1基因编码，已被证明可促进败血症小鼠的白细胞浸润和器官损伤。神经激肽-1受体(NK1R)是介导SP对脓毒症有害影响的主要受体。这项研究研究了SP是否影响粘附分子的表达，包括细胞间细胞粘附分子-1（ICAM1）和血管细胞粘附分子-1（VCAM1）在肝和肺的血管内皮细胞上，导致败血症小鼠这些组织中的白细胞浸润。在小鼠中通过盲肠结扎和穿刺(CLP)手术诱发脓毒症。通过删除Tac1基因来抑制SP的作用，阻塞NK1R,或将这两种方法结合起来。肝和肺组织中髓过氧化物酶的活性以及ICAM1和VCAM1的浓度，以及这些组织中血管内皮细胞上ICAM1和VCAM1的表达，被测量。肝和肺组织中髓过氧化物酶的活性和ICAM1和VCAM1的浓度，以及这些组织中血管内皮细胞上ICAM1和VCAM1的表达，在CLP手术诱导的脓毒症小鼠中增加。抑制SP的生物合成及其与NK1R的相互作用减弱了CLP手术诱导的小鼠肝脏和肺的改变。我们的发现表明，SP上调肝脏和肺中血管内皮细胞的ICAM1和VCAM1的表达，从而通过激活NK1R增加具有CLP手术诱导的脓毒症的小鼠的这些组织中的白细胞浸润。
