西维来司钠和丙泊酚对烧冲复合伤后犬急性肺损伤的疗效研究

发布时间：2018-04-09 05:25

本文选题：烧冲复合伤　切入点：西维来司钠　出处：《中国人民解放军医学院》2014年博士论文

【摘要】：目的：烧冲复合伤是由冲击波和烧伤共同作用造成的一种严重致命性创伤，烧冲复合伤一旦发生，其病情进展迅速、救治困难、病死率高，呼吸功能障碍是其主要和难治的并发症之一。本实验针对烧冲复合伤后的急性肺损伤和免疫功能障碍，拟评估两种药物的治疗效果：一是中性粒细胞弹性蛋白酶抑制剂西维来司钠，另一个是镇静镇痛药物丙泊酚，同时试图探讨药物可能的作用机制。方法一：健康级雄性Beagle犬32只，体质量（10.2±0.7）kg，（20.5±2.0)月龄，完全随机化分为四组：正常对照组、烧冲复合伤对照组、烧冲复合伤+小剂量西维来司钠治疗组、烧冲复合伤+大剂量西维来司钠治疗组各8只。建立烧冲复合伤模型后按Parkland公式补液，CT观察肺部大体损伤情况，分别于伤后2、6、12、24、48h，监测平均动脉压（MAP）、呼吸频率（RR）、血管外肺水（EVLW）、肺血管通透性指数（PVPI）、PaO2和PaCO2，ELISA法检测血清中中性粒细胞弹性蛋白酶（NE）及TNF-α，IL-8浓度；伤后48h将所有犬放血处死取肺组织测算肺湿干质量比，行肺病理HE染色。方法二：采用上述业已建立的烧冲复合伤模型，将32只雄性比格犬按随机数字表法分为：正常对照组、烧冲复合伤对照组、烧冲复合伤+小剂量丙泊酚治疗组、烧冲复合伤+大剂量丙泊酚治疗组各8只，除正常对照组外其余3组均致重度烧冲复合伤，，伤后按Parkland公式补液，烧冲复合伤+小剂量丙泊酚治疗组和烧冲复合伤+大剂量丙泊酚治疗组在补液同时分别连续输注2mg kg-1h-1和5mg kg-1h-1丙泊酚注射液，持续72h。4组实验动物伤后，在伤前、伤后6、24、48、72h分别采取外周静脉血5ml，监测PaO2和PaCO2，酶联免疫吸附法（ELISA）检测各组细胞间粘附分子（ICAM-1）和淋巴细胞功能相关抗原-1（LFA-1）水平；流式细胞仪检测各组CD14+单核细胞犬主要组织相容性复合体（MHC）抗原表达率；CD4+/CD8+T淋巴细胞比值和外周血单个核细胞（PBMC）凋亡率，肺病理HE染色。结果一：烧冲复合伤犬伤后EVLW、PVPI等明显增高，CT显示肺呈毛玻璃样变，RR增快，PaO2和PaCO2降低，其血清中NE、TNF-α和IL-8的浓度显著升高。给予大剂量西维来司钠后，可以有效降低重度烧冲复合伤犬血清中NE、TNF-α和IL-8的水平，降低EVLW和PVPI等血流动力学指标，减轻肺水肿，减慢RR，提高PaO2和PaCO2。结果二：烧冲复合伤犬伤后血清中ICAM-1和LFA-1的水平显著升高，其CD14+单核细胞表面MHC的表达率增高，CD4+/CD8+T淋巴细胞比值先升高后降低，PBMC凋亡率明显高于正常对照组。给予持续丙泊酚治疗后，可以提高PaO2和PaCO2，明显降低血清中ICAM-1和LFA-1的水平，以及MHC的表达率，升高CD4+/CD8+T淋巴细胞比值，减少PBMC凋亡率。结论：烧冲复合伤后早期应用西维来司钠可以减轻肺水肿，降低血清中炎症因子水平，改善血气分析指标，达到保护肺组织的治疗效果。丙泊酚则可能通过剂量依赖性的方式抑制ICAM-1过度释放和PBMC凋亡从而改善烧冲复合伤后免疫功能，减轻肺损伤。
[Abstract]:Objective : To investigate the effect of burn - in composite wound on acute lung injury and immune dysfunction caused by shock wave and burn .

Methods : 32 healthy male Beagle dogs , body mass ( 10.2 卤 0.7 ) kg , ( 20.5 卤 2.0 ) months old , were randomly divided into four groups : normal control group , burn - in compound injury control group , burn - in compound injury + small - dose sivita sodium treatment group .
All dogs were sacrificed 48 hours after injury to measure lung wet - dry mass ratio and lung pathology HE staining .

Methods : Thirty - two male Beagle dogs were randomly divided into two groups : normal control group , burn - in compound injury control group , burn - in compound injury + small - dose propofol group , burn - in compound injury + high - dose propofol treatment group .
Flow cytometry was used to detect the expression of MHC antigen in CD14 + monocytes in each group .
CD4 + / CD8 + T lymphocyte ratio and peripheral blood mononuclear cell ( PBMC ) apoptosis rate , lung pathology HE staining .

Results The results showed that EVLW , PVPI and so on were significantly increased after burn - in composite injured dogs . The results showed that the levels of NE , TNF - 伪 and IL - 8 in the serum of severely burned complex injured dogs were significantly increased . The levels of NE , TNF - 伪 and IL - 8 in the serum of severely burned complex injured dogs could be effectively reduced , the hemodynamics indexes such as EVLW and PVPI were decreased , pulmonary edema was reduced , RR was slowed , and PaCO 2 was increased .

Results 2 : The levels of ICAM - 1 and lfa - 1 in serum were significantly higher after burn - in , and the ratio of CD4 + / CD8 + T lymphocytes increased and the percentage of CD4 + / CD8 + T lymphocytes increased first , and the apoptosis rate of PBMC was significantly higher than that in the normal control group .

Conclusion : It is possible to reduce pulmonary edema , decrease the level of inflammatory factor in serum , improve the index of blood gas analysis , and improve the therapeutic effect of lung tissue . Propofol can inhibit the excessive release of ICAM - 1 and the apoptosis of PBMC by dose - dependent manner , so as to improve the immune function and reduce the lung injury .

【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R644

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