【摘要】：[目的]肺泡上皮細(xì)胞和血管內(nèi)皮細(xì)胞功能障礙以及氧自由基過量生成是急性肺損傷重要的病理生理特征。作為肺器官保存液,低鉀右旋糖酐液能保護(hù)肺泡上皮細(xì)胞和內(nèi)皮細(xì)胞的功能,減少脂質(zhì)過氧化,改善肺功能,已在肺移植臨床廣泛應(yīng)用。因此假設(shè)從外周靜脈全身給予低鉀右旋糖酐液能改善急性肺損傷發(fā)生后的肺功能,影響炎癥因子的濃度,對治療急性肺損傷發(fā)揮有益的作用。 [方法]將10頭健康的中華小型豬(3.9kg~6.2kg,4~6周齡,性別不拘)麻醉后直接向肺內(nèi)給予油酸,總量為0.1 ml/kg,誘導(dǎo)急性肺損傷。動物隨機(jī)分為2組,每組5頭：對照組：給予油酸前30分鐘從耳靜脈輸入乳酸林格液,總量為12.5ml/kg;處理組：給予油酸前30分鐘從耳靜脈輸入低鉀右旋糖酐液,總量為12.5ml/kg。以動脈血氧分壓/吸入氧濃度比值(氧合指數(shù))小于300mmHg為發(fā)生急性肺損傷的標(biāo)準(zhǔn)。分別于開胸后(基點(diǎn))、肺損傷發(fā)生時以及肺損傷發(fā)生后每1小時測定一次動脈血?dú)庵笜?biāo)、血流動力學(xué)指標(biāo)和血漿中腫瘤壞死因子α、內(nèi)皮素1、溶解型細(xì)胞間粘附分子1、白細(xì)胞介素10、白細(xì)胞介素1β和白細(xì)胞介素6的濃度,直到肺損傷發(fā)生后6小時處死動物。取肺組織,進(jìn)行組織學(xué)檢查,評價細(xì)胞凋亡,測定肺勻漿中腫瘤壞死因子α、內(nèi)皮素1、溶解型細(xì)胞間粘附分子1、白細(xì)胞介素10的濃度。 [結(jié)果]處理組動物在急性肺損傷發(fā)生后,動脈血pH(損傷后6小時,7.36±0.05vs 7.09±0.03,P0.01)和二氧化碳分壓明顯較對照組改善(P0.05或0.01),氧合指數(shù)升高(P0.05),平均肺動脈壓較對照組明顯下降(損傷后6小時21.4±5.0mmHg vs 39.2±0.8mmHg, P0.0l);處理組血漿中溶解型細(xì)胞間粘附分子1和內(nèi)皮素1的濃度較對照組明顯降低(P0.05),而血漿白細(xì)胞介素10濃度較對照組明顯升高(P0.05)；處理組肺的組織學(xué)損傷程度較對照組明顯減輕(肺組織學(xué)評分11.8±3.0 vs19.2±3.8,P0.01)；肺組織勻漿中腫瘤壞死因子α的濃度較對照組明顯降低(4.98±0.62pg/ml vs 11.31±4.80pg/ml, P0.05),兩組動物在肺損傷后細(xì)胞凋亡無明顯統(tǒng)計學(xué)差異(10.6±1.3個/高倍視野vs 9.5±1.3個/高倍視野,P=0.086)。 [結(jié)論]從外周靜脈滴注低鉀右旋糖酐液預(yù)處理可以改善油酸誘導(dǎo)的幼豬急性肺損傷后肺的氣體交換功能,降低肺動脈壓力,減輕肺的組織學(xué)損傷；降低血漿中溶解型細(xì)胞間粘附分子1和內(nèi)皮素1的濃度,升高血漿中白細(xì)胞介素10的濃度,降低肺組織中腫瘤壞死因子α的濃度。
[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 偽, 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 偽, 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 鹵0.05vs 7.09 鹵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 鹵5.0mmHg vs 39.2 鹵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 鹵3.0 vs19.2 鹵3.8 P0.01). The concentration of TNF- 偽 in lung homogenate was significantly lower than that in control group (4.98 鹵0.62pg/ml vs 11.31 鹵4.80 PG / ml, P0.05). There was no significant difference in apoptosis between the two groups after lung injury (10.6 鹵1.3 / vs 9.5 鹵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 偽 in lung tissue was decreased.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2011
【分類號】：R-332

【參考文獻(xiàn)】

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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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