Zhou Juan, Pavlovic Dragan, Rüb Johanna, Masur Stefan, Spassov Alexander, Whynot Sara, Hung Orlando, Kern Hartmut, Saleh Abdo Islam, Shukla Romesh, Cerny Vladimir, Lehmann Christian
Department of Anesthesia, Dalhousie University, Halifax, NS, Canada.
Department of Anesthesia and Intensive Care Medicine, Ernst Moritz Arndt University Greifswald, Greifswald, Germany.
Clin Hemorheol Microcirc. 2014;56(3):273-84. doi: 10.3233/CH-131743.
Intestinal microcirculatory disturbances play an important role in the pathophysiology of sepsis. A neural anti-inflammatory pathway has been suggested as a potential target for therapy that may dampen systemic inflammation. The aim of this study is to investigate the effects of physostigmine, a cholinesterase inhibitor, on the intestinal microcirculation and vascular contractility in experimental endotoxemia. Endotoxemia was induced in Lewis rats by intravenous lipopolysaccharide (LPS) administration. Animals were treated with either physostigmine or saline (control) following LPS challenge. The intestinal microcirculation, including leukocyte-endothelial interaction, functional capillary density (FCD) and non-perfused capillary density (NCD), was examined by intravital microscopy (IVM) 2 hours after LPS administration. The impact of physostigmine on vascular contractility of rat aortic rings was examined by in vitro myography. Physostigmine significantly reduced the number of adhering leukocytes in intestinal submucosal venules (V1 venules: -61%, V3 venules: -36%) of LPS animals. FCD was significantly increased by physostigmine treatment (circular muscle layer: +180%, longitudinal muscle layer: +162%, mucosa: +149%). Low concentrations of physostigmine produced significant contraction of aortic ring preparations, whereas high concentrations produced relaxation. In conclusion, physostigmine treatment significantly improved the intestinal microcirculation in experimental endotoxemia by reducing leukocyte adhesion and increasing FCD.
肠道微循环紊乱在脓毒症的病理生理学中起重要作用。一种神经抗炎途径已被认为是一种潜在的治疗靶点，可能会减轻全身炎症。本研究的目的是探讨胆碱酯酶抑制剂毒扁豆碱对实验性内毒素血症时肠道微循环和血管收缩性的影响。通过静脉注射脂多糖（LPS）在Lewis大鼠中诱导内毒素血症。在LPS攻击后，动物接受毒扁豆碱或生理盐水（对照）治疗。在给予LPS 2小时后，通过活体显微镜检查（IVM）检查肠道微循环，包括白细胞与内皮细胞的相互作用、功能性毛细血管密度（FCD）和非灌注毛细血管密度（NCD）。通过体外肌动描记法检查毒扁豆碱对大鼠主动脉环血管收缩性的影响。毒扁豆碱显著减少了LPS动物肠道黏膜下小静脉（V1小静脉：-61%，V3小静脉：-36%）中黏附白细胞的数量。毒扁豆碱治疗使FCD显著增加（环形肌层：+180%，纵形肌层：+162%，黏膜：+149%）。低浓度的毒扁豆碱使主动脉环标本产生显著收缩，而高浓度则产生舒张。总之，毒扁豆碱治疗通过减少白细胞黏附和增加FCD，显著改善了实验性内毒素血症时的肠道微循环。
