血清VEGF、TK-1和T淋巴细胞亚群与乙型肝炎病毒相关性肝病发生和进展的关系

Relationship between serum VEGF,TK-1,T lymphocyte subsets and the occurrence,progression of hepatitis B virus-related liver disease

目的:探讨血清血管内皮细胞生长因子(VEGF)、可溶性胸苷激酶-1(TK-1)和T淋巴细胞亚群与乙型肝炎病毒(HBV)相关性肝病的发生和进展的关系。方法:选择HBV相关性肝病病人188例,其中单纯乙型肝炎(乙肝)52例,肝纤维化40例,肝硬化56例,肝癌40例。另选择30名健康体检者为对照组。采用PCR法检测HBV-DNA负荷量,常规生化法检测肝功能指标丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)水平,ELISA法检测VEGF和TK-1水平,流式细胞术检测T淋巴细胞亚群CD3^(+)、CD4^(+)、CD8^(+)百分比和CD4^(+)/CD8^(+)。结果:单纯乙肝组、肝纤维化组、肝硬化组、肝癌组的HBV-DNA负荷量及ALT、AST水平差异均无统计学意义(P>0.05)。肝癌组、肝硬化组、肝纤维化组、单纯乙肝组、对照组VEGF和TK-1、CD4^(+)/CD8^(+)水平逐渐降低;各组CD3^(+)、CD4^(+)和CD8^(+)水平差异均无统计学意义(P>0.05)。HBV相关性肝病病人血清中VEGF与TK-1呈明显正相关关系(r=0.745,P<0.01),VEGF与CD4^(+)/CD8^(+)呈明显负相关关系(r=-0.217,P<0.01),TK-1与CD4^(+)/CD8^(+)呈明显负相关关系(r=-0.208,P<0.01)。结论:HBV相关性肝病病人血清中VEGF、TK-1和CD4^(+)/CD8^(+)水平与疾病的发生和进展相关,VEGF和TK-1表达升高、CD4^(+)/CD8^(+)下降可能参与了乙肝、肝纤维化、肝硬化和肝癌的发生和进展。

Objective:To investigate the relationship between serum vascular endothelial growth factor(VEGF),soluble thymidine kinase-1(TK-1),T lymphocyte subsets and the occurrence,progression of hepatitis B virus(HBV)-related liver disease.Methods:A total of 188 patients with HBV-related liver disease were selected,including 52 patients with simple hepatitis B,40 patients with liver fibrosis,56 patients with liver cirrhosis and 40 patients with liver cancer.Another 30 healthy people were selected as the control group.The HBV-DNA load was detected by PCR,the level of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) was determined by routine biochemical method,the level of VEGF and TK-1 was detected by ELISA,and T lymphocyte subsets including the percentage of CD3^(+),CD4^(+),CD8^(+) and the ratio of CD4^(+)/CD8^(+) were analyzed by flow cytometry.Results:There was no significant difference in HBV-DNA load,level of ALT and AST among simple hepatitis B group,liver fibrosis group,liver cirrhosis group and liver cancer group(P>0.05).The level of VEGF,TK-1 and CD4^(+)/CD8^(+) in liver cancer group,liver cirrhosis group,liver fibrosis group,simple hepatitis B group and control group decreased gradually,the difference of which was statistically significant(P0.05).In the serum of patents with HBV-related liver disease,VEGF level was significantly positively correlated with TK-1 level(r=0.745,P<0.01),VEGF level was significantly negatively correlated with CD4^(+)/CD8^(+)(r=-0.217,P< 0.01),and TK-1 level was significantly negatively correlated with CD4^(+)/CD8^(+)(r=-0.208,P<0.01).Conclusions:The level of VEGF,TK-1 and CD4^(+)/CD8^(+)in the serum of patients with HBV-related liver disease is related to the occurrence and progression of the disease.The up-regulation of VEGF,TK-1 and down-regulation of CD4^(+)/CD8^(+)may be involved in the occurrence and progression of hepatitis B,liver fibrosis,liver cirrhosis and liver cancer.