慢性乙型肝炎患者肝纤维化不同阶段DJ-1蛋白的表达与临床相关性研究

Study on the expression of DJ-1 protein in different stages of liver fibrosis in patients with chronic hepatitis B

目的:探讨DJ-1蛋白在乙型肝炎肝纤维化、肝硬化、肝癌各期患者肝组织中的表达及与临床相关性。方法:选取自2016年9月至2019年2月广西医科大学第一附属医院收治的经临床病理确诊的慢性乙型肝炎患者45例,分为乙肝肝纤维化组(纤维化组)、乙肝肝硬化组(肝硬化组)、肝癌组,每组15例,同期选取肝血管瘤15例为对照组。采用苏木精-伊红(HE)和天狼猩红(Sirius red)染色观察肝脏组织结构及纤维化的程度,采用免疫组织化学染色法观察并分析DJ-1蛋白在各组中的表达,探究DJ-1蛋白的表达与临床特征的相关性。结果:4组中谷氨酰胺转移酶(GGT)、天冬氨酸转移酶(AST)、谷丙转氨酶(ALT)、凝血酶原时间(PT)、血小板(PLT)、结合胆红素(DBIL)、甲胎蛋白(AFP)、凝血酶时间(TT)等指标比较,差异有统计学意义(均P<0.05),随着肝纤维化病情的进展(肝纤维化→肝硬化→肝癌),患者血清中GGT、AST、ALT、PT呈上升趋势,而PLT呈下降趋势。纤维化组,肝硬化组和肝癌组较对照组GGT、PT和PLT差异有统计学意义(P<0.05);与对照组相比,肝癌组AST和ALT差异有统计学意义(P<0.05),其中指标AST在纤维化组和肝癌组间存在显著差异(P<0.05)。DJ-1免疫组化结果显示,对照组DJ-1染色阳性平均光密度(AO值)最高,差异有统计学意义(P<0.05)。肝组织中DJ-1水平与肝纤维化Ishak评分、AFP、AST、ALT和TT呈负相关关系(P<0.05)。结论:DJ-1可能是延缓乙型肝炎肝纤维化进展的一个蛋白标志物。

Objective:To investigate the expression and the clinical relevance of DJ-1 protein in liver tissues of hepatitis B patients in stages of liver fibrosis,liver cirrhosis,and liver cancer.Methods:Forty-five patients with chronic hepatitis B diagnosed by clinicopathology and admitted to the First Affiliated Hospital of Guangxi Medical University from Sep.2016 to Feb.2019 were selected and divided into hepatitis B liver fibrosis group(fibrosis group),hepatitis B liver cirrhosis group(cirrhosis group),and liver cancer group,with 15 cases in each group.Fifteen cases of hepatic hemangioma in the same period were selected as the control group.HE and Sirius red staining were used to observe the structure of liver tissues and the degree of fibrosis.Immunohistochemical staining was used to observe the expression of DJ-1 protein in each group,and the correlation between the expression of DJ-1 protein and clinical characteristics was studied.Results:There were statistically significant difference in the indexes of glutamine transferase(GGT),aspartate transferase(AST),alkaline phosphatase(ALT),prothrombin time(PT),and platelet(PLT)among the 4 groups(All P<0.05).With the progress of liver fibrosis(liver fibrosis-liver cirrhosis-liver cancer),GGT,AST,ALT,DBIL,AFP,TT and PT in patients’serum showed an upward trend,while PLT showed a downward trend.The fibrosis group,liver cirrhosis group,and liver cancer group had statistically significant differences in GGT,PT,and PLT compared with the control group(P<0.05).AST and ALT in the liver cancer group were different from those of the control group(P<0.05).AST was significantly different between the fibrosis group and the liver cancer group(P<0.05).DJ-1 immunohistochemical results showed that the control group had the highest average optical density(AO value)of DJ-1 staining,and the difference was statistically significant(P<0.05).The level of DJ-1 in liver tissues was negatively correlated with Ishak score,AFP,AST,ALT,and TT(P<0.05).Conclusion:DJ-1 may be a protein marker for delays the progression of liver fibrosis in hepatitis B.