肝素对内毒素诱导急性肺损伤大鼠炎症反应的影响  

Effect of heparin upon inflammatory reaction of endotoxin-induced acute lung injury in rat

作　　者：孙辉明[1] 施毅[1] 宋勇[1] 林心情[1] 沈小昆[1] 洪灵芝[1] 

机构地区：[1]南京大学临床学院南京军区南京总医院呼吸内科,210002

出　　处：《中华医学杂志》2009年第38期2722-2725,共4页National Medical Journal of China

基　　金：江苏省六大人才高峰基金（2005A6）

摘　　要：目的探讨肝素对内毒素诱导急性肺损伤（ALI）大鼠炎症反应的影响及其相关机制。方法36只清洁级雄性SD大鼠按随机数字表法分为ALI组、肝素治疗组（肝素组）和正常对照组（对照组），每组12只。内毒素静脉注射复制大鼠ALI模型。建模后4h处死各组大鼠，采用改良Smith评分法进行肺组织形态学评分，单核素示踪技术测定肺微血管白蛋白通透性（Palb），酶联免疫吸附试验测定血清中肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）和血管假性血友病因子（vWF）含量，蛋白质印迹法检测肺组织细胞外信号调节激酶（ERK）1／2、P38丝裂原活化蛋白激酶（P38MAPK）和c-jun氨基端激酶（JNK）磷酸化蛋白表达。结果肝素组和ALI组大鼠肺组织Smith评分[分别为（5．00±1．26）、（8．00±1．09）分]均明显高于对照组[（0．67±0．52）分，均P〈0．01]，但肝素组明显低于ALI组（P〈0．01）。肝素组Palb、TNF-α、IL-6和vWF分别为0．28±0．04、（1．92±0．35）μg/L、（1．22±0．13）ng／m]和（24．9±4．0）U／L，虽然明显高于对照组[分别为0．20±0．02、（0．51±0．09）μg／L、（0．23±0．05）ng／ml和（14．0±3．0）U／L，均P〈0．01]，但明显低于ALI组[分别为0．38±0．04、（2．77±0．37）μg/L、（1．62±0．13）ng／ml和（31．8±7．5）U／L，均P〈0．01）]。ALI组ERK1／2、P38 MAPK的磷酸化表达明显高于对照组；肝素组ERK1／2、P38 MAPK的磷酸化表达虽然也高于对照组，但明显低于ALI组；各组间JNK磷酸化表达无明显差异。结论肝素明显抑制细胞内信号转导蛋白ERK1／2、P38 MAPK的磷酸化表达，下调TNF—α、IL-6等炎症介质水平，降低Palb，减轻血管内皮细胞的损伤，对内毒素血症介导的ALI有显著的防护作用。Objective To investigate the effects of heparin upon inflammatory reaction and associated mechanism of endotoxin-induced acute lung injury （ALI） in rat. Methods Thirty-six male Sprague-Dawley rats were randomly divided into three equal groups namely： ALI group, heparin treatment group and normal control group. The ALI rats were induced by injecting endotoxin intravenously and sacrificed at 4 h after model establishment. The lung histology was scored by a modification of Smith technique. The albumin permeability of pulmonary microvascular （Palb） was measured by single nuclide tracer technique. Tumor necrosis factor α （TNF-α）, interleukin 6 （IL-6） and von Willebrand factor （vWF） levels of serum were determined using commercial enzyme-linked immunosorbent assay kits. The expressions of lung tissue extacellular signal-regulated kinases （ERK）-1/2, P38 mitogen-activated protein kinase （MAPK） and c-jun N-terminal kinases （JNK） were determined by Western blotting. Results The Smith lung injury score in heparin treatment group and ALI group were （5. 00 ± 1.26） and （8. 00 ± 1.09） respectively. The values were significantly higher than that of normal control group （0. 67 ±0. 52, both P 〈 0. 01 ）. However, the Smith lung injury score in heparin treatment group was significantly lower than that of ALI group （P 〈 0. 01 ）. The Palb, TNF-α, IL-6 and vWF of heparin treatment group were （0. 28 ± 0.04 ）, （1.92±0.35） μg/L, （1.22 ±0.13） ng/ml and （24.9 ±4.0） U/L respectively. The values were significantly higher than those of normal control group [ 0. 20 ±0.02, （ 0. 51 ± 0. 09 ） μg/L, （0. 23 ± 0. 05 ） ng/ml and （ 14. 0 ± 3.0） U/L respectively, all P 〈 0. 01 ] but significantly lower than those of ALI group [ （0. 38±0. 04 ）, （2. 77 ±0. 37 ） μg/L, （ 1.62 ±0. 13 ） ng/ml and （ 31.8 ± 7. 5 ） U/L respectively, all P 〈0.01]. The lung tissue levels of phospho-ERK1/2 and phospho-P38 MAPK expressions of heparin treatment g

关 键 词：肝素 内毒素类 急性肺损伤 炎症 大鼠 

分 类 号：R686[医药卫生—骨科学]