Effect of free radical scavenger on cardiovascular system in sepsis

自由基清除剂对脓毒症心血管系统的影响

• 批准号: 16591562
• 负责人: SERITA Ryohei
• 金额: $ 2.3万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591562/
• 关键词: sepsis; cardiac function; free radical scavenger; nicaraven; cytokine; nicaraven

The purposes of present study were to determine the effects of nicaraven on cardiac function and cytokine production in lipopolysaccharide (LPS) induced sepsis.This protocol was approved by our institutional committee. Following arterial and venous cannulation and tracheostomy, rats (330-350 g) were anesthetized with pentobarbital, and mechanically ventilated with a control mode (TV = 12 ml/kg, RR = 40 rpm). After baseline measurements, rats (n = 20) were administrated with LPS (10 mg/kg, intravenously) and randomly assigned to following two groups : the nicaraven group treated with nicaraven (3 mg/kg/min, intravenously) and the control group treated with saline. The left ventricular, pressure and volume were measured with the pressure and conductance catheter every one hour. Cardiac function, including cardiac output (CO), ejection fraction (EF), and maximal elastance of left ventricle (E_<max>) were analyzed with a computer soft. Blood was collected, centrifuged (2000g, 15 min, x 2), and stored (-80 c) from rats every 2 hours after operation to measure plasma concentration of TNF-α, IL1-β and macrophage migration inhibitory factor (MIF) using enzyme-linked immunosorbent assays kits. Arterial blood gas analysis and lactate concentration were also measured. Data were analyzed by repeated measure ANOVA.The CO in the nicaraven group was kept significantly higher than the control group (p < 0.05). The EF and E_<max> in the nicaraven group were also kept significantly higher than the control group (p < 0.05). Arterial lactate, TNF-α, IL1-β and MIF were significantly lower in the nicaraven group versus the control group (P < 0.05).In conclusion, the current study indicates that the treatment with nicaraven preserves cardiac function and reduces plasma concentration of cytokine, and improves lactic acidosis in septic model.

本研究旨在探讨尼卡地文对脂多糖（LPS）诱导的脓毒症大鼠心功能和细胞因子产生的影响。在动脉和静脉插管和气管切开术后，用戊巴比妥麻醉大鼠（330-350 g），并以对照模式（TV = 12 ml/kg，RR = 40 rpm）进行机械通气。在基线测量之后，大鼠（n = 20）被给予LPS（10 mg/kg，静脉内）并被随机分配到以下两组：尼卡地文组（3 mg/kg/min，静脉内）给予尼卡地文，对照组给予生理盐水。每隔1h用压力和电导导管测量左心室压力和容积。用计算机软件分析心功能指标，包括心输出量（CO）、射血分数（EF）、左室最大弹性（E_<max>）。术后每隔2 h取血，离心（2000 g，15 min，× 2），保存（-80 ℃），用酶联免疫吸附测定试剂盒测定血浆TNF-α、IL-1-β和巨噬细胞移动抑制因子（MIF）浓度。同时测定动脉血气分析和乳酸浓度。重复测量方差分析结果显示，尼卡地文组的心输出量显著高于对照组（p &lt; 0.05）。尼卡地平组的EF、E_1<max>也显著高于对照组（P &lt; 0.05）。尼卡地平治疗组的动脉血乳酸、TNF-α、IL-1-β和MIF均显著低于对照组（P &lt; 0.05）。