肝肺综合征大鼠肺组织因子mRNA的表达及其意义

Lung expression of tissue factor mRNA and its significance in a rat model of hepatopulmonary syndrome

目的检测肝肺综合征（HPS）大鼠肺组织中组织因子（TF）mRNA的表达，探讨其意义。方法Sprague-Dawley雄性大鼠40只，均分为肝硬化组、肝肺综合征组，检测血气分析，用qRT—PCR检测肺组织TFmRNA的表达，光镜观察肺组织切片病理改变。两组间均数比较采用非参数分析Mann-WhitneyU检验，两因素之间的相关分析采用Spearman秩相关分析。结果（1）血气分析显示肝肺综合征组Pa02（58．20±3．19）mmHg低于肝硬化组的（85．00±2．53）mmHg，差异有统计学意义（P〈0．05）。（2）肺组织TFmRNA的表达在肝肺综合征组（相对表达量为0．77±0．22）明显高于肝硬化组（0．33士0．14），差异有统计学意义（P〈0．05）；其与Pa02呈显著负相关（r=-0．565，P〈0．05）。（3）肺组织病理学检查显示肝硬化组部分肺泡间隔增厚，肺泡腔大小不一，肺容量减少，炎性细胞浸润，局部肺血管内可见充血，肝肺综合征组肺泡间隔增宽明显，肺泡腔大小不一、有明显的出血，纤维素性渗出，大量炎性细胞浸润，肺容量减少，肺泡壁毛细血管扩张明显，局部增生，巨噬细胞聚集，微血栓形成。肝肺综合征组肺组织内微血栓形成，大鼠肺组织TFmRNA相对表达量为0．68土0．17，高于无血栓形成的大鼠的0．40±0．12，差异有统计学意义（P〈0．05）。结论肝肺综合征大鼠肺组织TFmRNA的表达升高，且随着缺氧程度的加重而加重，可能增加肝肺综合征肺血栓栓塞发生的风险。

Objective To determine the lung expression of tissue factor （TF） mRNA in hepatopulmonary syndrome （HPS） using a rat model system and to investigate the potential significance of its differential expression. Methods Forty male Sprague-Dawley rats were used to establish models of cirrhosis （n = 20） and HPS （n = 20）. Blood gas analysis was used to investigate the effects of each model on pulmonary fimction. Effects on the expression of TF mRNA in lung were determined by qRT- PCR and on lung pathology by histological analysis, Results The HPS rats showed significantly lower PaO2 than the cirrhosis rats （58.20 ± 3.19 mmHg vs. 85.00 ± 2.53 mmHg, P 〈 0.05） but significantly higher TF mRNA expression in lung （0.77 ± 0.22 vs. 0.33 ± 0.14, P 〈 0.05）. TF mRNA expression was negatively correlated with the value of PaO2 （r = -0.565, P 〈 0.05）. The lungs of the cirrhosis rats showed widened alveolar intervals, diversified sizes of alveolar spaces, reduced lung capacity, inflammatory cell infiltration, and hyperemia in the pulmonary vessels. The lungs of the HPS rats showed all of the same changes but also with accumulated macrophages and micro-thrombosis in the pulmonary vessels. Among the HPS rats, those with micro-thrombosis in pulmonary vessels showed a greater increase in TF mRNAexpression than those without （0.68± 0.17 vs. 0.40 ± 0.12, P 〈 0.05）. Conclusion The expression of TF mRNA in lung of hepatopulmonary syndrome model rats was elevated and might increase the incidence of thromboembolism in the lung.