战创伤致MODS模型中细胞因子的变化及血液净化的应用

发布时间：2018-07-05 16:09

本文选题：连续性血液净化 + 多器官功能障碍综合征　；参考：《中国人民解放军军医进修学院》2007年硕士论文

【摘要】： 目的：利用失血性休克、缺血-再灌注损伤及内毒素复合因素，模拟战创伤特点建立猪的多器官功能障碍综合征(multiple organ dysfunctionsyndrome，MODS)实验模型，分析血中细胞因子水平的变化，，探讨早期实施连续性血液净化(continuous blood purification，CBP)对战创伤致MODS主要器官功能及细胞因子的影响。方法：16只健康雄性猪，随机分为CBP组(n=6)和MODS组(n=10)。MODS组动物予放血总血容量的30～45％，维持2小时后开始液体复苏，复苏完毕后1小时予大肠杆菌内毒素(E. coli O_(55)：B_5)按100ug／kg在4-6小时内自外周静脉持续泵入，模拟战创伤特点建立MODS动物模型；CBP组于内毒素注射1小时后开始CBP治疗，采用高通量血液滤过(high-volume hemofiltration，HVHF)模式，治疗16～18小时；连续动态监测及器官功能支持，7天后处死存活动物。观察各时间点的外周血细胞计数、动脉血气及主要器官功能参数的变化，以ELISA法检测血清血管内皮生长因子(VEGF)、肿瘤坏死因子α(TNFα)、白介素-6(IL-6)、白介素-10(IL-10)的浓度，并观察MODS发生率和死亡率及主要器官病理学改变，分析VEGF与主要器官功能参数及炎症介质等变化趋势的相关性，比较存活与死亡动物的血清VEGF浓度，并比较CBP组与MODS组主要器官功能、血清细胞因子的水平及两组的死亡率。结果：模型成功率70％，注射内毒素1小时后TNFα、IL-6、IL-10均显著升高，病理学改变主要以非特异炎症改变为主。MODS死亡率达71.4％，发生3个器官功能障碍的有4例，发生4个或以上器官功能障碍的有3例，肺和胃肠衰竭的发生次数最多，而心脏衰竭及凝血功能障碍死亡率最高；在休克期及再灌注期血清VEGF水平升高，内毒素打击后明显降低，血清VEGF水平的变化趋势与AST、ALT、TBIL、Cr有负性相关(P＜0.05)，与外周血Plt变化趋势呈正性相关(P＜0.05)，与TNFα、IL-6、 (TNFα+IL-6)／IL-10比值的变化趋势亦有相关性(P＜0.05)，存活组血清VEGF水平高于死亡组(P＜0.05)；CBP组氧合指数高于MODS组，外周血AST、ALT、Cr明显低于MODS组，但两组外周血小板计数、血清TBIL浓度差异无统计学意义；CBP组血清TNFα、IL-6、IL-10水平均在CBP治疗3～7小时左右下降明显，之后逐渐升高接近于MODS组；CBP组治疗后血清VEGF水平高于MODS组；CBP组死亡率为16.7％，显著低于MODS组(71.4％)(P＜0.01)。结论：利用复合因素打击，可以模拟战创伤特点建立MODS动物模型，MODS时出现促炎／抗炎失衡，过度炎症反应可抑制VEGF的表达，血清VEGF水平与主要器官功能参数变化趋势有相关性，在MODS的发展中可能具有防御机制；早期CBP干预治疗能有效改善主要脏器功能，降低血中炎症介质水平，减弱炎症反应，可利于VEGF的表达，降低MODS的死亡率。
[Abstract]:Objective: to establish an experimental model of (multiple organ dysfunctional dysfunction syndrome (multiple organ dysfunctional syndrome mods) in pigs by using hemorrhagic shock, ischemia-reperfusion injury and endotoxin compound factors, and to analyze the changes of cytokines in blood. To investigate the effects of early continuous blood purification (continuous blood purificationus) on the function of major organs and cytokines of mods caused by war trauma. Methods Sixteen healthy male pigs were randomly divided into CBP group (n = 6) and mods group (n = 10). One hour after resuscitation, E. coli O _ (55: B _ 5) was continuously pumped into 100ug/kg from peripheral vein within 4-6 hours. The animal model of mods was established by simulating the characteristics of war trauma. The mods animal model was treated with 100ug/kg for 1 hour after endotoxin injection. The high-volume hemofiltration (HV) model was used to treat the animals for 16 to 18 hours, and the surviving animals were killed after 7 days of continuous dynamic monitoring and organ function support. The changes of peripheral blood cell count, arterial blood gas and main organ function parameters at different time points were observed. The serum levels of vascular endothelial growth factor (VEGF), tumor necrosis factor 伪 (TNF 伪), interleukin-6 (IL-6) and interleukin-10 (IL-10) were detected by Elisa. The incidence and mortality of mods and pathological changes of main organs were observed, and the correlation between VEGF and the changes of main organ function parameters and inflammatory mediators were analyzed, and the serum VEGF concentrations of surviving and dead animals were compared. The main organ function, serum cytokine level and mortality were compared between CBP group and mods group. Results: the success rate of the model was 70%. The level of IL-10 in TNF- 伪 and IL-6 was significantly increased 1 hour after endotoxin injection. The mortality rate of mods was 71.4%, and 4 cases had three organ dysfunction. There were 3 cases with 4 or more organ dysfunction, the incidence of pulmonary and gastrointestinal failure was the most frequent, the mortality of heart failure and coagulation dysfunction was the highest, and the level of serum VEGF increased during shock and reperfusion. Endotoxin was significantly reduced after hitting, There was a negative correlation between the level of serum VEGF and the level of TBILCr (P < 0.05), a positive correlation with the change trend of peripheral blood Plt (P < 0.05), and a change trend with the ratio of TNF 伪 IL-6, (TNF 伪 IL-6) / IL-10 (P < 0.05). The serum VEGF level in the survival group was higher than that in the dead group (P < 0.05). The oxygenation index of CBP group was higher than that of mods group, and the level of ASTtTncr in peripheral blood was significantly lower than that in mods group. However, there was no significant difference in peripheral platelet count and serum TBIL concentration between CBP group and CBP group. The level of serum VEGF in mods group was significantly higher than that in mods group (P < 0.01). The mortality rate of CBP group was significantly lower than that of mods group (71.4%) (P < 0.01). Conclusion: by using compound attack, the animal model of mods can be established by simulating the characteristics of war trauma. The imbalance of proinflammatory / anti-inflammatory was found in mods. Excessive inflammatory reaction could inhibit the expression of VEGF, and the level of serum VEGF was correlated with the change trend of main organ function parameters. Early CBP intervention therapy can effectively improve the main organ function, reduce the level of inflammatory mediators in blood, weaken the inflammatory response, which is conducive to the expression of VEGF and reduce the mortality of mods.
【学位授予单位】：中国人民解放军军医进修学院
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R82

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