循环血TLR-4、TGF-β1表达水平与HBV相关性肝硬化患者病情程度的相关性分析

Correlation analysis between expression levels of TLR-4, TGF-β1 in circulating blood and severity of patients with HBV related liver cirrhosis

目的检测Toll样受体4(TLR-4)、转化生长因子β1(TGF-β1)在乙型肝炎病毒(HBV)相关性肝硬化患者中的表达水平,探讨其在HBV相关性肝硬化发生、发展中的作用。方法选取2016年1月2017年12月川北医学院附属医院就诊的HBV携带者25例(HBV携带组),慢性乙型肝炎(CHB)患者50例(CHB组),HBV相关性肝硬化患者139例(HBV相关性肝硬化组),选取同期25例健康体检者为对照(健康对照组)。检测TLR-4、TGF-β1及HBV DNA在各研究对象循环血中的表达水平并检测肝功能指标。比较TLR-4、TGF-β1表达水平差异及与丙氨酸转氨酶(ALT)、HBV载量的相关性。结果HBV携带组循环血TLR-4、TGF-β1水平与健康对照组比较差异无统计学意义(P>0.05)。HBV相关性肝硬化组TLR-4、TGF-β1表达水平较健康对照组、HBV病毒携带组、CHB组水平升高(P<0.05),HBV相关性肝硬化组TLR-4、TGF-β1表达水平较CHB组升高(P<0.05);在HBV相关性肝硬化患者中,随着肝损或肝纤维化程度加重,循环血TLR-4、TGF-β1表达水平升高,Child-Pugh C级HBV相关性肝硬化患者循环血TLR-4、TGF-β1水平最高,Child-Pugh A、B、C级3者间比较,差异有统计学意义(P<0.05);HBV相关性肝硬化患者循环血TLR-4、TGF-β1水平与HBV DNA载量呈负相关(r=-0.497和-0.581,均P=0.000);与ALT水平呈正相关(r=0.572和0.619,均P=0.000);HBV相关性肝硬化患者循环血TGF-β1与TLR-4表达水平呈正相关(r=0.736,P=0.000)。结论HBV相关性肝硬化患者循环血TLR-4、TGF-β1高表达,可能诱导参与肝纤维化的发生,是反映HBV相关性肝硬化病情与纤维化程度的重要指标之一。

Objective To investigate the expression levels of Toll like receptor 4(toll-like receptor 4,TLR-4)and transforming growth factorβ1(trans-forming growth factorβ1,TGF-β1)and their roles in the occurrence and development of HBV related cirrhosis.Methods From January 2016 to December 2017,25 HBV carriers(HBV carrier group),50 CHB patients(CHB group)and 139 HBV related cirrhosis patients(HBV related cirrhosis group)were selected from the Affiliated Hospital of North Sichuan Medical College,and 25 healthy people were selected as the control group(healthy control group).The circulating blood samples of the study objects were selected.The expression of TLR-4,TGF-β1 in the circulating blood of all the subjects were detected by enzyme-linked immunosorbent assay(Elisa),the HBV DNA level of circulating blood was detected by fluorescence quantitative PCR method,and the liver function index was detected by ADVIA 2400 automatic biochemical analyzer.The expression level of TLR-4,TGF-β1 and their correlation with ALT,HBV load in the circulating blood were compared.Results There was no significant difference in circulating blood TLR-4,TGF-β1 levels between HBV carriers and healthy controls(P>0.05);the expression of TLR-4,TGF-β1 in circulating blood increased with the developed severity of HBV related liver disease;the highest expression levels of TLR-4,TGF-β1 were in patients with hepatitis B related cirrhosis,and those in patients with hepatitis B related cirrhosis were higher than in healthy controls,hepatitis B virus carriers and patients with CHB,and the difference was statistically significant(P<0.05);the expression of TLR-4,TGF-β1 in the hepatitis B related cirrhosis group was significantly higher than that in the CHB group,and the difference between the two groups was statistically significant(P<0.05);the expression level of TLR-4,TGF-β1 in circulating blood increased with the aggravation of liver damage or liver fibrosis;the highest level of TLR-4,TGF-β1 was found in hepatitis B related cirrhosis patients with Child-Pugh C,and the difference was statistically significant among patients with Child-Pugh A,B and C(P<0.05);the levels of TLR-4 and TGF-β1 in the circulatory blood of patients with hepatitis B associated with cirrhosis were negatively correlated with the HBV DNA load(r=-0.497 and-0.581,all P=0.000);there was a positive correlation between them and ALT level(r=0.572 and 0.619,all P=0.000);there was a positive correlation between TGF-β1 level in circulating blood and TLR-4 level in patients with hepatitis B associated cirrhosis(r=0.736,P=0.000).Conclusions High levels of TLR-4 and TGF-β1 in circulating blood of HBV related liver cirrhosis patients may induce the occurrence of liver fibrosis,which is one of the important indicators to reflect the degree of HBV related liver cirrhosis and fibrosis.