Department of Anesthesiology, University of Regensburg, Regensburg, Germany.
Department of Pathology, University of Regensburg, Regensburg, Germany.
Mediators Inflamm. 2019 Jan 20;2019:8274903. doi: 10.1155/2019/8274903. eCollection 2019.
Recent studies have shown that acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) may serve as important diagnostic and therapeutic targets in sepsis. Since polymorphonuclear neutrophils (PMNs) play a pivotal role in the early phase of sepsis, we evaluated the potential therapeutic effects of cholinesterase inhibitors on PMN functions during cecal ligation and puncture- (CLP-) induced sepsis and investigated the roles of AChE and BChE as inflammatory markers under standardized experimental conditions.
Sham surgery or CLP was performed in male Wistar rats ( = 60). Animals were randomized into four groups: physostigmine, 100 g/kg; neostigmine, 75 g/kg; 0.9% saline (control group); and sham group, each applied four times over 24 h. The levels of reactive oxygen species (ROS) production and CD11b/CD62l expression were quantified by flow cytometry at = 0, 6, 15, 20, and 24 h. Blood gas analysis as well as AChE and BChE activity levels was measured by validated point-of-care measurements. Clinical scores and survival times were determined.
CLP induced a significant increase in ROS production and CD11b upregulation by rat PMNs. Treatment with physostigmine or neostigmine significantly reduced ROS production and CD11b upregulation by PMNs 20 h after CLP induction. In physostigmine-treated animals, survival times were significantly improved compared to the control animals, but not in neostigmine-treated animals. While AChE activity significantly decreased in the control animals at > 6 h, AChE activity did not change in the sham group. BChE activity decreased at > 20 h in the control animals.
While AChE activity may serve as an acute inflammatory marker, BChE activity shows a delayed decrease. Administration of centrally acting physostigmine in CLP-induced sepsis in rats has protective effects on PMN functions and improves survival times, which may be of interest in clinical practice.
最近的研究表明，乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）可能作为脓毒症的重要诊断和治疗靶点。由于多形核粒细胞（PMN）在脓毒症的早期阶段发挥关键作用，我们评估了胆碱酯酶抑制剂对盲肠结扎和穿刺（CLP）诱导的脓毒症期间PMN 功能的潜在治疗效果，并在标准化实验条件下研究了 AChE 和 BChE 作为炎症标志物的作用。
雄性 Wistar 大鼠进行假手术或 CLP（=60）。动物随机分为四组：毒扁豆碱，100μg/kg；新斯的明，75μg/kg；0.9%生理盐水（对照组）；和假手术组，每组在 24 小时内应用 4 次。通过流式细胞术在 =0、6、15、20 和 24 小时时定量测定活性氧（ROS）产生和 CD11b/CD62l 表达。通过验证的即时护理测量来测量血气分析以及 AChE 和 BChE 活性水平。确定临床评分和存活时间。
CLP 诱导大鼠 PMN 中 ROS 产生和 CD11b 上调显著增加。与 CLP 诱导后 20 小时，用毒扁豆碱或新斯的明治疗可显著降低 PMN 中 ROS 的产生和 CD11b 的上调。与对照组动物相比，用毒扁豆碱治疗的动物的存活时间明显改善，但用新斯的明治疗的动物则没有。虽然 AChE 活性在对照组动物中 >6 小时后显著降低，但在假手术组中没有变化。BChE 活性在对照组动物中 >20 小时后降低。
虽然 AChE 活性可能作为急性炎症标志物，但 BChE 活性显示出延迟性降低。在 CLP 诱导的脓毒症大鼠中给予中枢作用的毒扁豆碱具有对 PMN 功能的保护作用，并提高存活时间，这在临床实践中可能具有重要意义。
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