第二军医大学 硕士学位论文 依达拉奉对大鼠失血性休克复苏后组织器官功能的影响 姓名：王莹 申请学位级别：硕士 专业：麻醉学 指导教师：邓小明 2011-04 依达拉奉对大鼠失血性休克复苏后组织器官功能的影响 - 1 - 摘 要 【目的】【目的】 本研究拟探讨依达拉奉对失血性休克复苏后大鼠血浆炎症因子（TNF-、IL-6） 水平以及组织器官功能和病理变化的影响。 【方法】【方法】 24 只雄性 SD 大鼠随机分成 3 组， 假手术组 （Sham 组） 、 生理盐水组 （NS 组） 、 依达拉奉治疗组（ED 组），每组 8 只。Sham 组大鼠仅行股动、静脉置管。NS 组 和 ED 组经股动、静脉置管放血诱导休克，将平均动脉压（MAP）维持于 35 45mmHg，持续 60min。休克期结束后，两组均给予 60%的自体血和 2 倍的乳酸林 格液复苏。分别在复苏即刻及结束时，NS 组给予生理盐水（2ml/kg），ED 组给予 依达拉奉（4mg/kg）。三组分别在置管血流动力学稳定后、复苏后 2h 及 24h 取血 检测血浆 TNF- 和 IL-6 以及血浆 ALT、AST、BUN 和 Cr 。复苏后 24h 时，三组 大鼠心脏抽血处死取左肺、肝左叶、左肾作病理学检测。复苏后 3、6、9、12、18、 24h 观察各组大鼠的存活情况。 【结果】【结果】 各组血浆 TNF-、IL-6 随时间的变化均有统计学差异（P0.01） ，其中复苏后 2h 时， NS 组明显高于 Sham 组 （P0.05） ， 而 ED 组与 NS 组无显著差异 （P0.05） 。 复苏后 24h 时，NS 组血浆 TNF-、IL-6 仍明显高于 Sham 组（P0.05） ，而 ED 组 明显低于 NS 组（P0.05） 。各组大鼠血浆 ALT、AST 在复苏后 24h 时，NS 组明显 高于 Sham 组（P0.05） ，而 ED 组显著低于 NS 组（P0.05） 。在复苏后 2h 时，NS 组血浆 BUN、 Cr 均显著高于 Sham 组 （P0.05） ， 而 ED 组明显低于 NS 组 （P0.05） ； 复苏 24h 时，NS 组大鼠血浆 BUN、Cr 仍显著高于 Sham 组（P0.05） ，而 ED 组血 浆 Cr 明显低于 NS 组（P0.05） ，但其 BUN 与 NS 组比较无显著性差异（P0.05） 。 复苏后 24h 时，NS 组肝、肾、肺脏均有明显的病理改变，而 ED 组病理改变程度均 有所减轻。NS 组与 ED 组大鼠生存率无显著差异。 【结论】【结论】 依达拉奉可明显降低失血性休克大鼠复苏后2h及24h血浆TNF-和IL-6水平， 减轻复苏后肝脏和肾脏损伤的指标以及 24h 时肝脏、肾脏、肺脏病理改变，但对复 苏后 24h 生存率无明显影响 第二军医大学硕士学位论文 - 2 - 【关键词】【关键词】 失血性休克，复苏，依达拉奉，炎症反应，氧化应激，自由基清除剂，肿瘤坏死因 子-，白细胞介素-6 依达拉奉对大鼠失血性休克复苏后组织器官功能的影响 - 3 - Abstract Objective The present study was to investigate the effects of edaravone on cytokine levels , tissues and organs function and pathological changes in rats with hemorrhagic shock and resuscitation. Methods 24 rats were randomly divided into 3 groups: the sham-operated control group (Sham), the haemorrhage shock goup (NS), and the haemorrhage shock with edaravone injection (ED) with 8 each group. Rats in the latter two groups were bled from a femoral artery catheter in 10 minutes with MAP maintained within the range of 35 to 45 mmHg for 60 minutes and resuscitaton was induced by reinjecting 60% autologous blood and 2 times shed blood Ringers. At the initiation and ending of resuscitation, Rats in NS group were given saline (2ml/kg) . Rats in ED group were given the same volume edaravone injection(4mg/kg) through the femoral vein. Two hours and 24 hours after the ending of resuscitation, plasma TNF-, IL-6, ALT, AST, BUN and Cr were measured separately. At 24 hour following resuscitation, the left lung , the left lobe of liver and the left kidney were taken for pathological evaluation. Survival of rats was observed within 24hours after resuscitation. Results Based on plasma ALT, AST, BUN, Cr levels, pathological evaluation , survival of rats and plasma interleukin-6 (IL-6) and tumor necrosis factor (TNF-) level of information, The results show: 2h after hemorrhagic shock and resuscitation, plasma TNF-a and IL-6 levels of rats in NS group were significantly higher than the sham group(p0.05). But there are no statistical significance between NS group and ED group(p0.05). 24h after hemorrhagic shock and resuscitation, plasma TNF-a and IL-6 levels of rats in NS group were also significantly higher than the sham group (p0.05) and the levels in ED group was significantly lower than the NS group. 24h after hemorrhagic shock and resuscitation, plasma ALT and AST levels of rats in NS group were significantly higher than the sham group (p0.05) and the levels in ED group was 第二军医大学硕士学位论文 - 4 - significantly lower than in the NS group. 2h after hemorrhagic shock and resuscitation, plasma BUN and Cr levels of rats in NS group were significantly higher than in the sham group(p0.05) and the levels in ED group was significantly lower than in the NS group(p0.05). 24h after hemorrhagic shock and resuscitation, plasma BUN and Cr levels of rats in NS group were also significantly higher than the sham group(p0.05) and the levels of Cr in ED group was significantly lower than in the NS group(p0.05).But the levels of BUN in ED group are no statistical significance compared to NS group (p 0.05). There were obvious pathological changes in liver, Kidney, and lung of rats in NS Group. But pathological changes were slight in ED Group. There were obvious pathological changes in liver, Kidney, and lung of rats in NS Group. But pathological changes were slight in ED Group. There was no significant difference in survival. Conclusions Our study suggests that plasma levels of TNF- and IL-6 after reperfusion were significantly increased. Treatment with edaravone suppressed the release of TNF-a and IL-6 and decreased the levels of markers of organ injury after induction of HS in rats. Edaravone can also reduce the pathological damage of tissues and organs and improve the survival rate of rats after resuscitation KEY WORDS: Hemorrhagic shock, resuscitation, Edaravone, Inflammation, Oxidative stress, Free radical scavenger, Tumor necrosis factor-, Interleukin-6 依达拉奉对大鼠失血性休克复苏后组织器官功能的影响 - 5 - 主要英文缩略词表 Abbreviation 英文缩写英文缩写 英文英文 中文中文 HS hemorrhagic shock; 失血性休克 ED edaravone 依达拉奉 ARDS acute respiratory distress syndrome 急性呼吸窘迫综合征 SIRS sys