【摘要】 目的观察西维来司钠对创伤失血性休克（THS）复苏后大鼠的保护作用及其可能的机制。方法将30只大鼠随机分为假手术组（sham组）、THS组、西维来司钠处理组（S组）,各10只。Sham组只行5 cm切口造成软组织创伤,不行放血和复苏;THS组和S组均完成腹部创伤、放血及液体复苏等处理,并在复苏前分别腹腔注射生理盐水、西维来司钠。复苏后即刻监测并记录各组大鼠血流动力学指标,复苏后24 h监测左心室压力最大上升速率(+dp/dt_max)和左心室压力最大下降速率(-dp/dt_max),检测动脉血气分析指标、肝肾功能指标、炎症因子[肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）、高迁移率族蛋白B1（HMGB1）],计算肺系数与肺湿/干重比,并在光学显微镜下观察心、肺、肝、肾细胞病理形态学改变。结果与sham组比较, THS组及S组心率、平均动脉压、+dp/dt_max及-dp/dt_max均下降,pH、PaO₂、HCO₃^-均降低,而PaCO₂、乳酸、W/D、肺系数、肝肾功能指标、TNF-α、IL-6、HMGB1均升高（均P<0.05）,心、肺、肝、肾细胞均存在不同程度水肿。与THS组比较,S组+dp/dt_max及-dp/dt_max、pH、PaO₂、HCO₃^-均升高,而PaCO₂、乳酸、W/D、肺系数、肝肾功能指标、TNF-α、IL-6、HMGB1水平均下降（均P<0.05）,心、肺、肝、肾细胞水肿程度减轻。结论西维来司钠能够改善THS复苏后大鼠心、肺、肝、肾功能,具有保护作用,这可能与其特异性抑制中性粒细胞弹性蛋白酶活性、减少损伤后炎性因子过度释放有关。更多还原

【Abstract】 Objective To observe the protective effect of sivelestat sodium on traumatic hemorrhagic shock（THS） rats after resuscitation and its potential mechanism.Methods Thirty rats were randomly divided into sham-opertion group（sham group）, THS group and sivelestat sodium treatment group（S Group）, with 10 rats in each group. Soft tissues injury developed by a 5 cm incision was conducted in the sham group without bleeding and resuscitation; the THS group and the S group both received treatment of developing abdominal trauma, blood-letting therapy and fluid resuscitation, and were intraperitoneally administered normal saline and sivelestat sodium, respectively, prior to resuscitation. The hemodynamic indexes of all rats were monitored and recorded at the right moment after resuscitation, the maximum of positive first derivative of left ventricular pressure( +dp/dt_max) and the maximum negative first derivative of left ventricular pressure(-dp/dt_max) were monitored after 24 hours of resuscitation, the arterial blood gas analysis indexes, liver and renal function indexes, inflammatory factors（tumor necrosis factorα[TNF-α], interleukin 6[IL-6] and high mobility group protein B1[HMGB1]） were measured, the lung penetration index and ratio of wet weight to dry weight（W/D） were calculated, and the pathomorphological changes of heart, lung, liver and kidney cells were observed under optical microscope.Results In comparison with the sham group, the THS group and the S group had lower heart rate, mean arterial pressure, +dp/dt_max,-dp/dt_max, pH, PaO₂ and HCO₃^-, as well as higher PaCO₂, lactate, W/D, lung penetration index, liver and renal function indexes, TNF-α, IL-6 and HMGB1（all P<0.05）, and also exhibited edema of heart, lung, liver and kidney cells in various degrees. As compared with the THS group, the S group obtained increased +dp/dt_max,-dp/dt_max, pH, PaO₂ and HCO₃^-, as well as declined PaCO₂, lactate, W/D, lung penetration index, liver and renal function indexes, TNF-α, IL-6 and HMGB1 levels（all P<0.05）, and processed alleviated edema of heart, lung, liver and kidney cells.Conclusion Sivelestat sodium can improve heart, lung, liver and kidney function of THS rats after resuscitation, exerts a protective effect, which may be related to its specific inhibition effect on neutrophil elastase activity and decreasing over-release of inflammatory factors after injury.更多还原