PDGF-BB在胆道闭锁患儿肝脏中的表达及其与上皮间质转化的相关性研究

Hepatic expression of PDGF-BB in infants with biliary atresia and its correlation with epithelial mesenchymal transition

目的探讨胆道闭锁(biliary atresia,BA)患儿肝脏中血小板源性生长因子-BB(platelet-derived growth factor,PDGF-BB)、锌指转录因子(Snail 1)和上皮间质转化(epithelial-mesenchymal transition,EMT)的表达情况以及三者之间的关系。方法回顾性分析2018年1月至2019年12月河北医科大学第二医院小儿外科收治的BA患儿25例(BA组)、胆总管囊肿患儿15例(CCC组)以及肝脏肿瘤患儿10例(NL组)的临床资料;收集患儿活检组织,分别应用免疫组织化学法、实时荧光定量PCR检测PDGF-BB、Snail 1、E钙黏素(E-cadherin)和N钙黏素(N-cadherin)的表达情况,并对上述指标进行相关性分析。结果BA组患儿肝脏中PDGF-BB、Snail 1和N-cadherin的mRNA和蛋白表达均显著高于CCC组和NL组,差异有统计学意义(P<0.05),E-cadherin的mRNA和蛋白表达均显著低于CCC组和NL组,差异有统计学意义(P<0.05)。其中PDGF-BB与Snail 1 mRNA和蛋白的表达呈正相关(r=0.772,P<0.05;r=0.780,P<0.05);PDGF-BB与N-cadherin mRNA和蛋白表达呈正相关性(r=0.835,P<0.05;r=0.702,P<0.05);PDGF-BB与E-cadherin mRNA和蛋白表达呈负相关(r=-0.756,P<0.05;r=-0.696,P<0.05);Snail 1与N-cadherin mRNA和蛋白表达呈正相关(r=0.723,P<0.05;r=0.702,P<0.05);Snail 1与E-cadherin mRNA和蛋白表达呈负相关(r=-0.720,P<0.05;r=-0.636,P<0.05)。肝纤维化程度与PDGF-BB的表达呈正相关(r=0.977,P<0.05);肝纤维化程度与E-cadherin蛋白表达呈负相关(r=-0.722,P<0.05);肝纤维化程度与N-cadherin蛋白表达呈正相关(r=0.711,P<0.05);肝纤维化程度与Snail 1表达呈正相关(r=-0.810,P<0.05)。结论PDGF-BB可能通过增强转录因子Snail 1的转录活性,促进BA患儿发生EMT,这为BA患儿的诊治提供了新的理论依据。

Objective To explore the hepatic expression of platelet-derived growth factor-BB(PDGF-BB),Snail 1 and epithelial-mesenchymal transition(EMT)in children of biliary atresia(BA)and examine the relationship among three parameters.Methods From January 2018 to December 2019,there were BA(n=25),choledochal cysts(CCC,n=15)and liver tumors(NL,n=10).After collecting biopsy tissues,immunohistochemistry and real-time fluorescent quantitative polymerase chain reaction(PCR)were employed for detecting the expression of PDGF-BB,Snail 1,E-cadherin and N-cadherin and analyzing their correlations.Results mRNA and protein expressions of PDGF-BB,Snail 1 and N-cadherin were significantly higher in liver of BA group than those of CCC/NL group(P<0.05);mRNA and protein expressions of E-cadherin were significantly lower than that of CCC/NL group(P<0.05).PDGF-BB was correlated positively with Snail 1 mRNA and protein expressions(r=0.772,P<0.05;r=0.780,P<0.05);PDGF-BB was correlated positively with N-cadherin mRNA and protein expressions(r=0.835,P<0.05;r=0.702,P<0.05);PDGF-BB and E-cadherin mRNA and protein expressions were correlated negatively(r=-0.756,P<0.05;r=-0.696,P<0.05);Snail 1 and N-cadherin mRNA and protein expression were correlated positively(r=0.723,P<0.05;r=0.702,P<0.05);Snail 1 was correlated negatively with E-cadherin mRNA and protein expressions(r=-0.720,P<0.05;r=-0.636,P<0.05).Conclusion In BA children,PDGF-BB may promote EMT through enhancing the transcription activity of transcription factor Snail 1.Thus it may provide new theoretical rationales for diagnosing and treating BA children.