Du Yue, Wu Yu-bin, Cai Xu-xu, Han Yu-kun
Department of Pediatrics, the Second Hospital of China Medical University, Shenyang, 110004, China.
Zhonghua Er Ke Za Zhi. 2004 Sep;42(9):649-53.
To further explore the pathogenesis of neonatal acute lung injury and neonatal pulmonary hemorrhage by establishing the animal model of neonatal acute lung injury (ALI) and by investigating the changes of platelet endothelial cell adhesion molecule-1 (PECAM-1), tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) in ALI.
Totally 88 neonatal rats which were divided into 8 groups randomly including one normal saline control group and 30 min, 1 h, 2 h, 4 h, 8 h, 16 h and 24 h post injection groups. The changes of lung pathology in newborn rats were observed at different time after LPS was injected intraperitoneally. The changes of PECAM-1 protein, t-PA and PAI-1 mRNA expression were measured by immunohistochemistry and RT-PCR.
The expression of PECAM-1 protein and mRNA was decreased and the lowest level was reached at 8 h and 16 h post injection, respectively. The average values were 95.1 +/- 9.76 and 0.861 +/- 0.016, respectively, which were significantly lower than those in the control group (129.5 +/- 6.15, 1.192 +/- 0.035, P < 0.01). The expression of t-PA and PAI-1 mRNA was increased after LPS was injected. The highest level of t-PA mRNA expression was observed at 2 h after injection. The average value was 1.195 +/- 0.036, which was significantly higher than that in the control group (0.781 +/- 0.017, P < 0.01). The highest level of PAI-1 mRNA expression was observed at 2 h, 4 h and 8 h post injection. The average values were 1.178 +/- 0.069, 1.153 +/- 0.036 and 1.176 +/- 0.044, respectively, which was significantly higher than those of the control group (0.681 +/- 0.019, P < 0.01).
The expression of PECAM-1 protein and mRNA was decreased after LPS injection, suggesting the disruption of the tissue protective mechanism; the expression of t-PA and PAI-1 mRNA was increased, indicating the presence of a hypercoagulability state. At the same time, the expression of t-PA mRNA was increased which caused the extra-cellular matrix degradation at the early phase after LPS injection. These three phenomena might be the contributory factors to pulmonary hemorrhage.
通过建立新生儿急性肺损伤(ALI)动物模型,研究血小板内皮细胞黏附分子-1(PECAM-1)、组织型纤溶酶原激活物(t-PA)和纤溶酶原激活物抑制剂-1(PAI-1)在ALI中的变化,进一步探讨新生儿急性肺损伤和新生儿肺出血的发病机制。
将88只新生大鼠随机分为8组,包括1个生理盐水对照组和注射后30分钟、1小时、2小时、4小时、8小时、16小时和24小时组。腹腔注射脂多糖(LPS)后不同时间观察新生大鼠肺病理变化。采用免疫组织化学和逆转录-聚合酶链反应(RT-PCR)检测PECAM-1蛋白、t-PA和PAI-1 mRNA表达的变化。
PECAM-1蛋白和mRNA表达降低,分别在注射后8小时和16小时达到最低水平。平均值分别为95.1±9.76和0.861±0.016,显著低于对照组(129.5±6.15,1.192±0.035,P<0.01)。注射LPS后t-PA和PAI-1 mRNA表达增加。t-PA mRNA表达在注射后2小时达到最高水平。平均值为1.195±0.036,显著高于对照组(0.781±0.017,P<0.01)。PAI-1 mRNA表达在注射后2小时、4小时和8小时达到最高水平。平均值分别为1.178±0.069、1.153±0.036和1.176±0.044,显著高于对照组(0.681±0.019,P<0.01)。
注射LPS后PECAM-1蛋白和mRNA表达降低,提示组织保护机制破坏;t-PA和PAI-1 mRNA表达增加,表明存在高凝状态。同时,注射LPS后早期t-PA mRNA表达增加导致细胞外基质降解。这三种现象可能是肺出血的促成因素。