脾脏酪氨酸激酶促进肝肺综合征大鼠肺血管新生

Splenic tyrosine kinase promotes pulmonary angiogenesis in rats with hepatopulmonary syndrome

本研究旨在研究脾脏酪氨酸激酶(spleen tyrosine kinase,Syk)在肝肺综合征(hepatopulmonary syndrome,HPS)血管新生过程中的作用及其机制。Sprague Dawley(SD)大鼠随机分为3组:假手术组(Sham组)、胆总管结扎(common bile duct ligation,CBDL)5周组(5W组)和R788药物干预组(R788组),通过CBDL术进行HPS造模,R788组大鼠在CBDL术后每日腹腔注射1次R788(20 mg/kg)至第5周。用Western blot和免疫组织化学法检测Syk、p-Erk1/2、p-Akt在肺组织中的表达和分布情况,用免疫荧光染色法观察Syk在肺中的定位和肺组织血管新生数目。结果显示,相对Sham组,5W组大鼠Syk蛋白表达水平显著上调,Erk1/2和Akt磷酸化水平显著上调,肺微血管数量显著增加;相对5W组,R788组大鼠Syk蛋白表达水平显著下调,Erk1/2和Akt磷酸化水平显著下调,肺微血管数量显著减少。以上结果表明,Syk可能通过激活下游Erk1/2和Akt信号转导通路促进HPS模型大鼠肺内血管新生,这为HPS的临床治疗提供了理论依据和潜在药物治疗靶点。

The present paper was aimed to study the role of spleen tyrosine kinase(Syk)in angiogenesis in hepatopulmonary syndrome(HPS)and the underlying mechanism.Sprague Dawley(SD)rats were randomly divided into three groups:sham operation group(sham group),common bile duct ligation(CBDL)5-week group(5 W group)and R788 intervention group(R788 group).HPS model was established by CBDL.Rats in R788 group were intraperitoneally injected with R788(20 mg/kg)once daily to week 5 after CBDL operation.The protein expression levels and distribution of Syk,p-Erk1/2,and p-Akt in lung tissue were detected by Western blot and immunohistochemistry.Immunofluorescence staining was used to observe the location of Syk expression and the number of angiogenesis in lung tissue.The results showed that,compared with sham group,5 W group exhibited up-regulated protein expression level of Syk,increased phosphorylation levels of Erk1/2 and Akt,and increased number of pulmonary microvessels.Compared with 5 W group,R788 group exhibited down-regulated protein expression level of Syk,decreased phosphorylation levels of Erk1/2 and Akt,and decreased number of pulmonary microvessels.These results suggest that Syk may promote pulmonary angiogenesis in HPS model rats by activating downstream Erk1/2 and Akt signaling pathways,which provides a theoretical basis and potential drug therapeutic targets for the clinical treatment of HPS.