去氨加压素可改善实验性内毒素血症时肠道功能性毛细血管密度并降低白细胞活化。

Desmopressin improves intestinal functional capillary density and decreases leukocyte activation in experimental endotoxemia.

作者信息

Wafa K, Lehmann C, Wagner L, Drzymulski I, Wegner A, Pavlovic D

机构信息

Department of Anesthesia, Dalhousie University, Halifax, NS, Canada.

Department of Anesthesia, Dalhousie University, Halifax, NS, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada; Department of Pharmacology, Dalhousie University, Halifax, NS, Canada; Department of Anesthesiology and Intensive Care Medicine, Ernst Moritz Arndt University, Greifswald, Germany.

出版信息

Microvasc Res. 2015 Jan;97:98-104. doi: 10.1016/j.mvr.2013.09.001. Epub 2013 Sep 13.

DOI:10.1016/j.mvr.2013.09.001

PMID:24035754

Abstract

BACKGROUND

Blood flow to the intestine is decreased in sepsis in favor of vital organs resulting in ischemic damage of the gut mucosa. Once the mucosa is damaged, increased translocation of intestinal bacteria to the systemic circulation may occur. This in turn aggravates the inflammatory response contributing to the development of multi-organ failure. Desmopressin is a synthetic analog of vasopressin, an anti-diuretic hormone which has been shown to induce vasodilation and is thought to be implicated in immunomodulation. In this study, we investigate the effects of desmopressin on the intestinal microcirculation during sepsis in an experimental endotoxemia model in rats using intravital microscopy. In addition, we investigate the effects of desmopressin on systemic inflammation.

METHODS

Forty Lewis rats were subdivided into four groups, where rats received intravenous saline (control), desmopressin (1μg/kg/ml), lipopolysaccharide (5mg/kg) or lipopolysaccharide followed by desmopressin. Inflammatory response was assessed by quantifying the number of temporary and firmly adherent leukocytes in submucosal venules. Capillary perfusion was determined by assessing the number of functional, non-functional and dysfunctional capillaries in the intestinal wall layers (muscularis longitudinalis, muscularis circularis and mucosa). Additionally, inflammatory cytokine levels were determined by multiplex assays.

RESULTS

The number of firmly adhering leukocytes in V1 venules of rats receiving lipopolysaccharide and treated with desmopressin was significantly reduced compared to lipopolysaccharide only group (LPS: 259±25.7 vs. LPS+DDAVP: 203±17.2; n/mm(2); p<0.05). Additionally, desmopressin treatment improved impaired intestinal microcirculation by improving functional capillary density following lipopolysaccharide administration in all examined layers of the intestinal wall. We also observed a significant decrease in TNF-α levels in rats which received desmopressin in endotoxemia compared to untreated rats (LPS: 383±64.2; LPS+DDAVP: 261.3±22; pg/ml; p<0.05).

CONCLUSION

Desmopressin administration improved intestinal capillary perfusion and reduced inflammatory response in rat endotoxemia.

摘要

背景

脓毒症时肠道血流减少，优先供应重要器官，导致肠黏膜缺血性损伤。一旦黏膜受损，肠道细菌向体循环的易位可能增加。这反过来会加重炎症反应，促使多器官功能衰竭的发生。去氨加压素是血管加压素的合成类似物，血管加压素是一种抗利尿激素，已被证明可诱导血管舒张，并被认为与免疫调节有关。在本研究中，我们使用活体显微镜，在大鼠实验性内毒素血症模型中研究去氨加压素对脓毒症期间肠道微循环的影响。此外，我们还研究了去氨加压素对全身炎症的影响。

方法

40只Lewis大鼠分为四组，分别静脉注射生理盐水（对照组）、去氨加压素（1μg/kg/ml）、脂多糖（5mg/kg）或脂多糖后再注射去氨加压素。通过量化黏膜下小静脉中临时和牢固黏附的白细胞数量来评估炎症反应。通过评估肠壁各层（纵肌层、环肌层和黏膜）中功能性、非功能性和功能失调性毛细血管的数量来确定毛细血管灌注。此外，通过多重检测法测定炎症细胞因子水平。

结果

与仅注射脂多糖的组相比，注射脂多糖并接受去氨加压素治疗的大鼠V1小静脉中牢固黏附的白细胞数量显著减少（脂多糖组：259±25.7 vs. 脂多糖+去氨加压素组：203±17.2；个/mm(2)；p<0.05）。此外，去氨加压素治疗通过改善脂多糖给药后肠壁所有检查层的功能性毛细血管密度，改善了受损的肠道微循环。我们还观察到，与未治疗的大鼠相比，内毒素血症中接受去氨加压素治疗的大鼠肿瘤坏死因子-α水平显著降低（脂多糖组：383±64.2；脂多糖+去氨加压素组：261.3±22；pg/ml；p<0.05）。