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目的探讨内皮素-1及其受体在大鼠肝肺综合征(HPS)发病机制中的作用。方法分别采用RT-PCR和原位杂交方法检测HPS大鼠肺组织内皮素前体原(ppET-1)mRNA水平及两种亚型内皮素-1(ET-1)受体ETRA和ETRB在HPS大鼠肺组织的分布和表达。结果HPS大鼠肺组织ppET-1mRNA表达显著升高(0.48±0.06),为假手术(Sham)组表达量(0.21±0.04)的2.3倍(t=2.4114,P<0.05)。HPS大鼠肺血管ETRA的分布及染色强度与Sham组比较无明显变化,染色面积和平均积分光密度值与Sham组比较差异无统计学意义(P>0.05),而ETRB在远端肺小动脉和小静脉内膜上表达明显增强,尤以静脉明显。ETRB染色面积和平均积分光密度值明显高于Sham组(P<0.001)。结论HPS大鼠肺组织ET-1基因表达水平升高。ET-1在HPS大鼠肺血管的总体反应可能由于ETRB表达的增高而表现为扩张。
Objective To investigate the role of endothelin-1 and its receptor in the pathogenesis of hepatopulmonary syndrome (HPS) in rats. Methods The levels of endothelin-1 (proETP) mRNA and the expression of endothelin-1 (ETTR) receptor ETRA and ETRB in lung of HPS rats were detected by RT-PCR and in situ hybridization respectively. Distribution and Expression of Lung Tissue in Rats. Results The expression of ppET-1mRNA in the lung tissue of HPS rats was significantly increased (0.48 ± 0.06), 2.3-fold higher than that in sham group (0.21 ± 0.04) (t = 2.4114, P <0.05). The distribution and staining intensity of ETRA in pulmonary vessels of HPS rats showed no significant difference compared with Sham group, and there was no significant difference in staining area and average integral optical density between Sham group and Hm rats (P> 0.05) And small venules intima significantly increased expression, especially in the veins. ETRB staining area and average integrated optical density values were significantly higher than Sham group (P <0.001). Conclusion The expression of ET-1 gene in lung tissue of HPS rats increased. The overall response of ET-1 to the pulmonary blood vessels of HPS rats may appear to be dilated by the increase of ETRB expression.