全身给予低钾右旋糖酐液对油酸诱导的幼猪急性肺损伤模型的影响
发布时间：2018-11-02 06:53
【摘要】：[目的]肺泡上皮细胞和血管内皮细胞功能障碍以及氧自由基过量生成是急性肺损伤重要的病理生理特征。作为肺器官保存液,低钾右旋糖酐液能保护肺泡上皮细胞和内皮细胞的功能,减少脂质过氧化,改善肺功能,已在肺移植临床广泛应用。因此假设从外周静脉全身给予低钾右旋糖酐液能改善急性肺损伤发生后的肺功能,影响炎症因子的浓度,对治疗急性肺损伤发挥有益的作用。 [方法]将10头健康的中华小型猪(3.9kg~6.2kg,4~6周龄,性别不拘)麻醉后直接向肺内给予油酸,总量为0.1 ml/kg,诱导急性肺损伤。动物随机分为2组,每组5头：对照组：给予油酸前30分钟从耳静脉输入乳酸林格液,总量为12.5ml/kg;处理组：给予油酸前30分钟从耳静脉输入低钾右旋糖酐液,总量为12.5ml/kg。以动脉血氧分压/吸入氧浓度比值(氧合指数)小于300mmHg为发生急性肺损伤的标准。分别于开胸后(基点)、肺损伤发生时以及肺损伤发生后每1小时测定一次动脉血气指标、血流动力学指标和血浆中肿瘤坏死因子α、内皮素1、溶解型细胞间粘附分子1、白细胞介素10、白细胞介素1β和白细胞介素6的浓度,直到肺损伤发生后6小时处死动物。取肺组织,进行组织学检查,评价细胞凋亡,测定肺匀浆中肿瘤坏死因子α、内皮素1、溶解型细胞间粘附分子1、白细胞介素10的浓度。 [结果]处理组动物在急性肺损伤发生后,动脉血pH(损伤后6小时,7.36±0.05vs 7.09±0.03,P0.01)和二氧化碳分压明显较对照组改善(P0.05或0.01),氧合指数升高(P0.05),平均肺动脉压较对照组明显下降(损伤后6小时21.4±5.0mmHg vs 39.2±0.8mmHg, P0.0l);处理组血浆中溶解型细胞间粘附分子1和内皮素1的浓度较对照组明显降低(P0.05),而血浆白细胞介素10浓度较对照组明显升高(P0.05)；处理组肺的组织学损伤程度较对照组明显减轻(肺组织学评分11.8±3.0 vs19.2±3.8,P0.01)；肺组织匀浆中肿瘤坏死因子α的浓度较对照组明显降低(4.98±0.62pg/ml vs 11.31±4.80pg/ml, P0.05),两组动物在肺损伤后细胞凋亡无明显统计学差异(10.6±1.3个/高倍视野vs 9.5±1.3个/高倍视野,P=0.086)。 [结论]从外周静脉滴注低钾右旋糖酐液预处理可以改善油酸诱导的幼猪急性肺损伤后肺的气体交换功能,降低肺动脉压力,减轻肺的组织学损伤；降低血浆中溶解型细胞间粘附分子1和内皮素1的浓度,升高血浆中白细胞介素10的浓度,降低肺组织中肿瘤坏死因子α的浓度。
[Abstract]:Objective: dysfunction of alveolar epithelial cells and vascular endothelial cells and excessive production of oxygen free radicals are important pathophysiological features of acute lung injury. As a preservation solution of lung organs, low potassium dextran solution can protect the function of alveolar epithelial cells and endothelial cells, reduce lipid peroxidation, improve lung function, and has been widely used in lung transplantation. Therefore, hypothetical hypokalemic dextran solution can improve the lung function after acute lung injury, affect the concentration of inflammatory factors, and play a beneficial role in the treatment of acute lung injury. [methods] Ten healthy Chinese miniature pigs (3.9 kg / 6.2kg / 4w, 6 weeks old) were anesthetized and injected oleic acid directly into the lungs, the total amount of which was 0. 1 ml/kg, to induce acute lung injury. Animals were randomly divided into two groups: control group (n = 5): control group: 30 minutes before oleic acid was given, Ringer lactate was infused from ear vein, the total amount was 12.5 ml / kg; Treatment group: 30 minutes before oleic acid was given, low potassium dextran solution was infused from ear vein, the total amount was 12.5 ml / kg. The ratio of arterial partial pressure of oxygen to inhaled oxygen concentration (oxygenation index) was less than 300mmHg as the standard of acute lung injury. Arterial blood gas index, hemodynamic index and plasma tumor necrosis factor 伪, endothelin 1, soluble intercellular adhesion molecule 1 were measured after thoracotomy (BP), lung injury and every 1 hour after lung injury. The concentrations of IL 10, IL 1 尾 and IL 6 were killed 6 hours after lung injury. Lung tissue was taken for histological examination, apoptosis was evaluated, and the concentrations of tumor necrosis factor 伪, endothelin 1, soluble intercellular adhesion molecule 1 and interleukin 10 in lung homogenate were measured. [results] after acute lung injury, pH in arterial blood (7.36 卤0.05vs 7.09 卤0.03 P0.01) and partial pressure of carbon dioxide in treatment group were significantly improved than those in control group (P0.05 or 0.01). The oxygenation index increased (P0.05), and the mean pulmonary artery pressure decreased significantly compared with the control group (21.4 卤5.0mmHg vs 39.2 卤0.8mmHg, P0.01) at 6 hours after injury. The plasma concentrations of soluble intercellular adhesion molecule-1 and endothelin 1 in the treatment group were significantly lower than those in the control group (P0.05), while the concentration of interleukin 10 in plasma was significantly higher than that in the control group (P0.05). The degree of lung histologic injury in the treatment group was significantly less than that in the control group (lung histological score 11.8 卤3.0 vs19.2 卤3.8 P0.01). The concentration of TNF- 伪 in lung homogenate was significantly lower than that in control group (4.98 卤0.62pg/ml vs 11.31 卤4.80 PG / ml, P0.05). There was no significant difference in apoptosis between the two groups after lung injury (10.6 卤1.3 / vs 9.5 卤1.3, P < 0.086). [conclusion] Pretreatment with low potassium dextran solution from peripheral vein can improve the gas exchange function of lung after acute lung injury induced by oleic acid, reduce pulmonary artery pressure and alleviate lung tissue injury. The concentration of soluble intercellular adhesion molecule-1 and endothelin 1 was decreased, the concentration of interleukin 10 in plasma was increased, and the concentration of tumor necrosis factor 伪 in lung tissue was decreased.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2011
【分类号】：R-332
本文编号：2305267
[Abstract]:Objective: dysfunction of alveolar epithelial cells and vascular endothelial cells and excessive production of oxygen free radicals are important pathophysiological features of acute lung injury. As a preservation solution of lung organs, low potassium dextran solution can protect the function of alveolar epithelial cells and endothelial cells, reduce lipid peroxidation, improve lung function, and has been widely used in lung transplantation. Therefore, hypothetical hypokalemic dextran solution can improve the lung function after acute lung injury, affect the concentration of inflammatory factors, and play a beneficial role in the treatment of acute lung injury. [methods] Ten healthy Chinese miniature pigs (3.9 kg / 6.2kg / 4w, 6 weeks old) were anesthetized and injected oleic acid directly into the lungs, the total amount of which was 0. 1 ml/kg, to induce acute lung injury. Animals were randomly divided into two groups: control group (n = 5): control group: 30 minutes before oleic acid was given, Ringer lactate was infused from ear vein, the total amount was 12.5 ml / kg; Treatment group: 30 minutes before oleic acid was given, low potassium dextran solution was infused from ear vein, the total amount was 12.5 ml / kg. The ratio of arterial partial pressure of oxygen to inhaled oxygen concentration (oxygenation index) was less than 300mmHg as the standard of acute lung injury. Arterial blood gas index, hemodynamic index and plasma tumor necrosis factor 伪, endothelin 1, soluble intercellular adhesion molecule 1 were measured after thoracotomy (BP), lung injury and every 1 hour after lung injury. The concentrations of IL 10, IL 1 尾 and IL 6 were killed 6 hours after lung injury. Lung tissue was taken for histological examination, apoptosis was evaluated, and the concentrations of tumor necrosis factor 伪, endothelin 1, soluble intercellular adhesion molecule 1 and interleukin 10 in lung homogenate were measured. [results] after acute lung injury, pH in arterial blood (7.36 卤0.05vs 7.09 卤0.03 P0.01) and partial pressure of carbon dioxide in treatment group were significantly improved than those in control group (P0.05 or 0.01). The oxygenation index increased (P0.05), and the mean pulmonary artery pressure decreased significantly compared with the control group (21.4 卤5.0mmHg vs 39.2 卤0.8mmHg, P0.01) at 6 hours after injury. The plasma concentrations of soluble intercellular adhesion molecule-1 and endothelin 1 in the treatment group were significantly lower than those in the control group (P0.05), while the concentration of interleukin 10 in plasma was significantly higher than that in the control group (P0.05). The degree of lung histologic injury in the treatment group was significantly less than that in the control group (lung histological score 11.8 卤3.0 vs19.2 卤3.8 P0.01). The concentration of TNF- 伪 in lung homogenate was significantly lower than that in control group (4.98 卤0.62pg/ml vs 11.31 卤4.80 PG / ml, P0.05). There was no significant difference in apoptosis between the two groups after lung injury (10.6 卤1.3 / vs 9.5 卤1.3, P < 0.086). [conclusion] Pretreatment with low potassium dextran solution from peripheral vein can improve the gas exchange function of lung after acute lung injury induced by oleic acid, reduce pulmonary artery pressure and alleviate lung tissue injury. The concentration of soluble intercellular adhesion molecule-1 and endothelin 1 was decreased, the concentration of interleukin 10 in plasma was increased, and the concentration of tumor necrosis factor 伪 in lung tissue was decreased.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2011
【分类号】：R-332
【参考文献】
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1 ;Protective effects of glycine pretreatment on brain-death donor liver[J];Hepatobiliary & Pancreatic Diseases International;2005年01期
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