Boyd John H, Holmes Cheryl L, Wang Yingjin, Roberts Haley, Walley Keith R
Critical Care Research Laboratories, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada V6Z 1Y6.
Resuscitation. 2008 Nov;79(2):325-31. doi: 10.1016/j.resuscitation.2008.07.006.
The early use of vasopressors in sepsis has been associated with a decrease in immune activation independent of hemodynamic effects, although the mechanism behind this remains unclear. We hypothesize that low dose vasopressin will reduce the pulmonary inflammation associated with sepsis. Our aims were to (1) determine whether vasopressin reduces lipopolysaccharide (LPS)-induced pulmonary inflammation and (2) determine which vasopressin receptor is responsible for pulmonary immune modulation. Mice were treated with intraperitoneal LPS to induce both systemic and pulmonary inflammation. Vasopressin or saline was infused via peritoneal pump and interleukin 6 (IL-6) in lung and serum was measured at 6h. NF-kappaB activation as was determined in the lung through immunoblotting total and phospho-IkappaB. Hemodynamic data was also obtained at the 6h mark. In a separate series of experiments mice received both LPS and vasopressin infusion following pretreatment with vasopressin receptor antagonists to V1R, V2R and OTR. Low dose LPS dramatically raises both serum IL-6 and pulmonary levels of IL-6 and phospho-IkappaB despite no significant changes in mean arterial pressure at 6h. Compared to saline, vasopressin infusion significantly decreases both the pulmonary IL-6 levels and phospho-IkappaB in LPS treated mice without raising arterial pressure. Pretreatment with V2R antagonist results in complete attenuation of vasopressin's immunosuppressive effects, with restoration of pulmonary IL-6 and phospho-IkappaB levels to those seen with LPS alone.
Vasopressin exerts a local anti-inflammatory effect on the lung through the V2R in a model of sepsis.
脓毒症中早期使用血管升压药与免疫激活的降低有关，且与血流动力学效应无关，尽管其背后的机制尚不清楚。我们假设低剂量血管加压素会减轻与脓毒症相关的肺部炎症。我们的目的是：（1）确定血管加压素是否能减轻脂多糖（LPS）诱导的肺部炎症；（2）确定哪种血管加压素受体负责肺部免疫调节。通过腹腔注射LPS处理小鼠以诱导全身和肺部炎症。通过腹腔泵输注血管加压素或生理盐水，并在6小时时测量肺和血清中的白细胞介素6（IL-6）。通过免疫印迹总IκB和磷酸化IκB来确定肺中的NF-κB激活情况。在6小时时也获取血流动力学数据。在另一系列实验中，小鼠在分别用血管加压素V1R、V2R和OTR受体拮抗剂预处理后，接受LPS和血管加压素输注。尽管在6小时时平均动脉压无显著变化，但低剂量LPS显著提高了血清IL-6以及肺部IL-6和磷酸化IκB的水平。与生理盐水相比，血管加压素输注显著降低了LPS处理小鼠的肺部IL-6水平和磷酸化IκB，且未升高动脉压。用V2R拮抗剂预处理可完全消除血管加压素的免疫抑制作用，使肺部IL-6和磷酸化IκB水平恢复到仅用LPS时的水平。
在脓毒症模型中，血管加压素通过V2R对肺发挥局部抗炎作用。
