乙型肝炎病毒感染对Wnt/β-catenin信号通路的影响机制研究

Study on the effect of Hepatitis B virus infection on the Wnt/β-catenin signaling pathway

目的探讨研究乙型肝炎病毒(hepatic B virus,HBV)感染对患者Wnt/β-catenin信号通路的影响及其临床意义。方法研究收集西安交通大学第一附属医院2014年8月-2018年8月初治HBV感染患者300例,所有患者均接受肝脏穿刺活检,取得的标本进行石蜡包埋,此为试验组。另外选取100名健康志愿者肝脏组织标本作为对照组。采用高通量实时荧光定量PCR技术、Western blot方法分别检测试验组与对照组患者Wnt以及β-catenin的表达水平。300例HBV感染患者中,有156例患者合并肝硬化为肝硬化组,144例患者未合并肝硬化为非肝硬化组,采用实时荧光定量聚合酶链式反应法(Polymerase Chain Reaction,PCR)、Western blot法分别检测两组患者的Wnt、β-catenin的表达水平,评估HBV对于Wnt/β-catenin信号通路的影响。结果与对照组相比,试验组患者的Wnt-1以及β-catenin的蛋白质、mRNA表达水平均升高(P<0.05);试验组患者肝脏组织的Wnt-1以及β-catenin表达的阳性率分别为26.0%和25.3%,较对照组的9.0%和8.0%高(P<0.05);与非肝硬化组相比,肝硬化组患者的肝脏组织的Wnt-1以及β-catenin的蛋白质、mRNA表达水平均升高(P<0.05);肝硬化组患者肝脏组织的Wnt-1以及β-catenin表达的阳性率分别为34.0%和32.1%,较非肝硬化组的15.3%和13.2%高(P<0.05)。结论HBV患者的Wnt/β-catenin信号通路相关因素Wnt-1以及β-catenin的表达升高,且Wnt以及β-catenin的表达与HBV感染后肝脏病变进展程度密切关联。

OBJECTIVE To investigate the effect of hepatitis B virus(HBV)infection on Wnt/β-catenin signaling pathway and its clinical significance.METHODS Total of 300 patients with HBV infection treated in the First Affiliated Hospital of Xi’an Jiaotong University from August 2014 to August 2018 were enrolled.Livers of all patients in observation group were biopsied and their specimens were embedded in paraffin.Liver tissue samples in another 100 volunteers under physical examination during this period were selected as the control group.High-throughput real-time quantitative polymerase chain reaction(PCR)technology and Western blot assay were used to detect the expression levels of Wnt andβ-catenin in both groups.Among 300 HBV-infected patients,156 patients had cirrhosis,and 144 patients did not have cirrhosis.Real-time fluorescent quantitative PCR and Western blot was used to detect expression levels of Wnt andβ-catenin in both groups of patients,and to evaluate the effect of HBV on Wnt/β-catenin signaling pathway.RESULTS Compared with patients in the control group,Wnt-1 andβ-catenin protein and mRNA expression levels in the observation group were significantly elevated(P<0.05);positive rates of Wnt-1 andβ-catenin expression in the liver tissue of the observation group patients were 26.0%and 25.3%,respectively,which were significantly higher than that in the control group with 9.0%and 8.0%(P<0.05).Compared with the non-cirrhotic group,the Wnt-1 andβ-catenin proteins and mRNA expression level were significantly increased in liver tissue of patients with cirrhosis group(P<0.05).The positive rates of Wnt-1 andβ-catenin expression in liver tissues of patients with liver cirrhosis were 34.0%and 32.1%,respectively,which was significantly higher than that the non-liver cirrhosis group with 15.3%and 13.2%(P<0.05).CONCLUSION The expression of Wnt-1 andβ-catenin factors correlated with Wnt/β-catenin signaling pathway increased in HBV patients,which was closely related to the degree of liver disease progression after HBV infection.