肾上腺髓质素和内皮素-1在大鼠肝肺综合征发病机制中的作用

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[目的]探讨肝肺综合征(HPS)的发病机制。[方法]采用胆总管结扎(CBDL)术制备大鼠HPS模型,观察肺组织肾上腺髓质素(ADM)、内皮素1(ET1)及其受体(ETRA和ETRB)的表达和分布。[结果]在大鼠HPS形成过程中,血浆和肺组织中ADM、ET1水平动态升高,且与肺泡动脉氧分压差(A aDO2)正相关;HPS大鼠肺组织中ADM、内皮素前体原(ppET1mRNA)的表达较假手术组明显增强,差异均有统计学意义(P<0.05)。HPS大鼠肺血管ETRA的分布及染色强度与假手术组比较无明显变化,而ETRB在远端肺小动脉和小静脉内膜上表达明显增强。图像分析结果显示CBDL5周(w)组大鼠ETRA染色面积、平均积分光密度值与假手术组比较差异无统计学意义(P>0.05),而CBDL5w组大鼠ETRB染色面积和平均积分光密度值明显高于假手术组,差异均有统计学意义(P<0.05)。[结论]扩血管物质ADM和缩血管物质ET1的共同作用可能参与HPS的发生,肺组织中升高的ET1可能更多地通过与在肺血管表达增强的ETRB结合从而扩张肺血管。 [Objective] To investigate the pathogenesis of hepatopulmonary syndrome (HPS). [Method] The model of HPS was established by bile duct ligation (CBDL) to observe the expression and distribution of adrenomedullin (ADM), endothelin 1 (ET1) and their receptors (ETRA and ETRB) in lung tissue. [Results] During the process of rat HPS formation, the levels of ADM and ET1 in plasma and lung tissue increased dynamically and were positively correlated with the differential pressure of oxygen in alveolar artery (A aDO2). The levels of ADM, endothelin The expression of ppET1 mRNA was significantly higher than that in sham operation group (P <0.05). The distribution and staining intensity of ETRA in pulmonary vessels of HPS rats showed no significant changes compared with sham operation group, while the expression of ETRB in distal pulmonary arterioles and venules of small venules was significantly enhanced. The results of image analysis showed that there was no significant difference in ETRA staining area and average integral optical density between CBDL5w group and sham operation group (P> 0.05), while CBDL5w group rats ETRB staining area and average integral optical density Value was significantly higher than sham group, the difference was statistically significant (P <0.05). [Conclusion] The combination of vasodilator ADM and vasoconstrictor ET1 may be involved in the pathogenesis of HPS. Elevated ET1 in lung tissue may expand the pulmonary vessels more by binding to ETRB with enhanced expression in pulmonary vessels.
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