ET-1、NO、NOS、ETB受体在大鼠肝肺综合征作用中的初步研究

目的探讨内皮素-1（endothelin-1,ET-1）、内皮素B（endothelin B,ETB）受体、一氧化氮合酶（nitric oxide synthase,NOS）、一氧化氮（nitric oxide,NO）在大鼠肝肺综合征作用中的机制。方法雄性Wistar大鼠共33只随机分为3组,正常对照组（Control）、胆总管结扎组（common bileduct ligation,CBDL）和肝前门静脉高压（partial portal vein ligation,PVL）组。分别对对照组和PVL组术后5周以及CBDL组术后2、3和5周进行检测：门静脉压力、血气分析、肝功能以及血清一氧化氮（NO）、内皮素-1（ET-1）、肺组织内ETB受体、一氧化氮合酶诱导型（iNOS）、一氧化氮合酶内皮型（eNOS）蛋白表达水平,肝、肺病理,并使用激光多普勒血流仪检测肝、肺微循环进行检测。结果 CBDL组和对照组相比肝功能检测中白蛋白降低,胆红素、AST均升高;血气分析中PaO2降低,肺泡动脉氧分压差（AaPO2）增大;肝脏毛细血管血流量降低（P〈0.05）;肺脏毛细血管血流量增大（P〈0.05）;血浆内ET-1,NO水平增高;肺脏组织内eNOS,ETB受体蛋白表达增高（P〈0.05）;且病理检查CBDL组大鼠的肝脏组织可见胆汁性纤维化表现,肺组织可见肺毛细血管扩张、充血,证实HPS大鼠模型制成。PVL组大鼠与对照组相比,除门静脉压力和组织内ETB受体蛋白表达增高外（P〈0.05）,其余指标的差异有无统计学意义。肺脏组织内eNOS蛋白表达在三组间的表达无统计学意义。结论在CBDL建立的HPS大鼠模型中,可能是ET-1可被肝脏过量生成,进入血循环,与肺脏血管内皮细胞上的ETB受体结合,增加eNOS的表达和活性,NO产生增多,引起肺内血管扩张,进一步引起肝肺综合征（HPS）。

The preliminary study of the ET-1,NO,NOS,ETB acceptor taking the role in hepato-pulmonary syndrome( HPS) of rat model

Objective To discusses the mechanism of the ET-1,NO,NOS,ETB acceptor taking the role in hepato-pulmonary syndrome of rat model.Methods 33 male Wistar rats were divided into 3 groups at random:normal control group(Control),common bileduct ligation group(CBDL)and partial portal vein ligation(PVL)group.Separately Control group and PVL group postoperation at fifth week,as well as CBDL group after the HPS models established successfully at second week,third week and fifth week carries on as following detections:portal venous pressure(PVP),blood gas analysis,Hepatic function,nitrogen monoxidum(NO)and endothelin-1(ET-1)in blood serum,and ETB acceptor,iNOS,eNOS protein expression level in the lung tissues,and microcirculations of lung and liver measured by Laser Doppler Perfusion Monitor.Results Comparing with control group portal venous pressure(PVP),the bilirubin and AST in hepatic function examination,AaPO2 in blood gas analysis,the concentrations of serum NO,ET-1,and the level of ETB acceptor,the level of eNOS protein expression in the lung tissue,microcirculations of lung increased in CBDL group.But Comparing with control group the albumin in hepatic function examination,PaO2 in blood gas analysis,microcirculations of liver decreased in CBDL group.The bile canaliculi proliferation and hepatic fibrosis induced by cholestasis could be seen in the liver tissues of CBDL group rats pathology,and telangiectasis and congestion in lung tissues.It proved that HPS rats’models had been established.Apart from portal venous pressure and the level of ETB acceptor protein expression in the lung tissue remarkably increased(P<0.05)in PVL group compared with Control group,there is no-significance difference in other detections between the two groups.There is no significance difference among the above three groups about the level of eNOS protein expression in the lung tissue.Conclusion In the establishment rats’ HPS model by CBDL,possibly excessive production of ET-1 in the liver enters the blood circulation and integrate with endothelial cell on ETB acceptor,that increases the expression and activeness of eNOS making NO increase.As a result,excessive NO causes the vasodilatation in the lung and further results in HPS.