肝素对急性肺损伤/急性呼吸窘迫综合征的治疗作用

Therapeutic effects of heparin on acute lung injury or acute respiratory distress syndrome in rabbits

研究抗凝治疗对急性肺损伤/急性呼吸窘迫综合征动物模型的治疗作用及其机制。方法将48只大耳白兔随机分为四组:对照组(A组)、内毒素组(B组)、内毒素+肝素组(C组)和内毒素+低分子肝素组(D组),每组12只。肺损伤动物模型采用静脉注射脂多糖来制作,用NovaStstProfileM血气分析仪进行血气分析;用酶联免疫吸附测定(ELISA)法测定肿瘤坏死因子-α(TNF-α);用Westernblots检测磷酸化p38MAPK水平。结果①给予内毒素各组的动脉血氧分压(PaO2)进行性下降,1h后各时间点B、C、D组的PaO2显著低于A组(P<0.05);在4h和6h时,C组和D组PaO2明显高于B组(P<0.05),但C、D组之间差异均无统计学意义。②给予内毒素各组的血浆TNF-α水平进行性升高,在1h后各时间点B、C、D组的血浆TNF-α水平均显著高于A组(P<0.05);在4h和6h时,C组和D组血浆TNF-α水平明显低于B组(P<0.05),C、D组之间差异无统计学意义。③根据肺损伤的病理改变,A、B、C和D组的肺损伤评分分别为0.1分、(2.4±0.5)分、(1.6±0.5)分和(1.8±0.4)分,C、D组的肺损伤评分明显低于B组P<0.05)。④各实验组动物予以内毒素处理1h后p38MAPK的表达较对照组显著升高(P<0.05),C、D组在4h后p38MAPK表达明显低于B组(P<0.05),但C、D组之间差异无统计学意义。结论对于内毒素诱导的ALI动物模型,肝素和LMWH干预可能对ALI有一定的保护作用,表现在改善低氧血症和减轻炎症反应,减轻炎症反应可能与其抑制p38MAPK的活化有关。

Objective To investigate the potential beneficial effects and mechanism of heparin and low molecular weight heparin （ LMWH ） on rabbits with acute lung injury （ALI ） or acute respiratory distress syndrome （ARDS）. Methods Rabbit ALI model was established by intravenous injection with lipopolysaccharide （LPS）. 48 rabbits were randomly divided into four groups （n = 12） ： normal control group （group A） ,LPS group （group B） , LPS add heparin group （group C） and LPS add LMWH group （group D）. The blood gas analysis was performed; enzyme -linked immunosorbentassay was used to measure the level of TNF - α ; and western blots was used to measure the expression of p38 MAPK. Resuits ①The level of PaO2 was decreased after injection of LPS. At 4 and 6 hours after injection, the levels of PaO2 in group C and D were higher than that in group B （ P 〈 0.05 ）. There was no significant difference between group C and D. ②The level of TNF - α was increased after injection of LPS. At 4 and 6 hours after injection, the levels of TNF - α in group C and D was lower than that in group B （ P 〈 0. 05 ）. There was no significant difference between group C and D. ③The scores of lung injury in group A, B, C and D were 0.1, 2.4 ± 0.5, 1.6 ± 0.5 and 1.8± 0.4, respectively. The scores of lung injury in group C and D were lower than that in group B （ P 〈 0.05 ）. ④The expression of p38 MAPK was increased after injection of LPS. At 4 and 6 hours after injection, the expressions of p38 MAPK in group C and D were lower than that in group B （ P 〈 0.05 ）. There was no significant difference in the expression of p38 MAPK between group C and D. Conclusion Heparin and LMWH show their beneficial effects on rabbit ALI model in both functional and morphological aspects, including improving hypoxemia and lesse- ning inflammatory reaction. The mechanism of lessening inflammatory reaction may be related to the decrease of the expression of p38 MAPK.