核糖核苷酸还原酶小亚基M2在慢性HBV感染及其他肝病中的表达及意义

Expression and clinical significance of ribonucleotide reductase small subunit M2 in chronic HBV infection and other liver diseases

目的探讨核糖核苷酸还原酶小亚基M2(Ribonucleotide reductase small subunit M2,RRM2)在慢性乙型肝炎病毒(HBV)感染及其他肝病中的表达及临床意义。方法收集松阳县人民医院2017年10月至2019年9月慢性HBV感染及肝病患者共428例,其中慢性乙型肝炎(Chronic hepatitis B,CHB)患者166例[根据病毒载量不同,分为高病毒载量组(HBV DNA≥4.0 lgIU/mL,n=87)和低病毒载量组(HBV DNA<4.0 lg IU/mL,n=79),高病毒载量组患者根据丙氨酸转氨酶(ALT)水平不同,分为ALT≥40 U/L组(n=56)和ALT<40 U/L组(n=31)],HBV相关肝硬化53例,非HBV相关肝硬化28例,HBV相关肝癌57例,非HBV相关肝癌33例,非病毒性肝炎91例。另选取本院健康体检者36名为对照组。采用酶联免疫吸附法检测患者血清RRM2蛋白的表达水平,分析其与HBV DNA及肝功能之间的关系。应用SPSS 23.0和PRISM 8.0统计软件分析数据。相关性分析采用Spearman分析。结果CHB患者中,高病毒载量组的ALT和血清RRM2水平均高于低病毒载量组(Z=-6.68,t=6.80,P值均<0.01)。HBV相关肝硬化患者的血清RRM2水平高于非HBV相关肝硬化患者(t=9.16,P<0.01)。HBV相关肝癌组患者的血清RRM2水平高于非HBV相关肝癌组患者(t=12.42,P<0.01)。高病毒载量CHB患者中,ALT≥40 U/L组患者的血清RRM2水平与ALT<40 U/L组患者比较,差异无统计学意义(t=0.51,P>0.05)。非病毒性肝炎组ALT水平高于健康对照组(Z=-8.43,P<0.01),但两组血清RRM2水平比较,差异无统计学意义(t=1.03,P>0.05)。相关性分析显示,在慢性HBV感染及其相关肝病患者中,血清RRM2水平与HBV DNA载量呈正相关(r=0.51,P<0.01),与ALT、天冬氨酸转氨酶等肝功能指标无明显相关性(P值均>0.05)。结论血清RRM2水平与HBV DNA载量呈正相关,与ALT无明显相关性,RRM2有望成为乙型肝炎新药研发的靶点。

Objective To investigate the expression and clinical significance of ribonucleotide reductase small subunit M2(RRM2)in chronic hepatitis B virus(HBV)infection and related liver diseases.Methods A total of 428 patients with chronic HBV infection and liver disease were enrolled from Songyang County People’s Hospital from October 2017 to September 2019.There were 166 cases of chronic hepatitis B(CHB),53 cases of HBV-related cirrhosis,28 cases of non-HBV-related cirrhosis,57 cases of HBV-related liver cancer,33 cases of non-HBV-related liver cancer,and 91 cases of non-viral hepatitis.In addition,36 healthy subjects were selected as the control group.Among 166 cases of CHB,there were 87 patients with high viral load group(HBV DNA≥4.0 lg IU/mL)and 79 patients with low viral load group(HBV DNA<4.0 lg IU/mL);while in 87 high viral load patients,56 had high alanine transaminase(ALT)(≥40 U/L)and 31 had normal ALT(<40 U/L).The expression level of serum RRM2 protein in patients was detected by enzyme-linked immunosorbent assay(ELISA),and the relationship of RRM2 expression with HBV DNA and liver function was analyzed.SPSS 23.0 and PRISM 8.0 statistical software were used to analyze data.Correlation analysis was performed using Spearman analysis.Results The serum ALT and RRM2 levels in patients with high viral load CHB were higher than those in low viral load group(Z=-6.68,t=6.80,P<0.01).Patients with HBV-related cirrhosis had higher serum RRM2 levels than those with non-HBV-related cirrhosis(t=9.16,P<0.01).The serum RRM2 level was higher in patients with HBV-related liver cancer than that in patients with non-HBV-related liver cancer(t=12.42,P<0.01).Among patients with high viral load CHB,there was no significant difference in serum RRM2 levels between patients with ALT≥40 U/L group and patients with ALT<40 U/L group(t=0.51,P>0.05).The level of ALT in the non-viral hepatitis group was higher than that in the healthy control group(Z=-8.43,P<0.01),but there was no significant difference in serum RRM2 levels between the two groups(t=1.03,P>0.05).Correlation analysis showed that serum RRM2 level was positively correlated with HBV DNA load(r=0.51,P<0.01),but not correlated with liver function indicators such as ALT and aspartate aminotransferase(all P>0.05)in patients with chronic HBV infection and related liver diseases.Conclusions Serum RRM2 level is positively correlated with HBV DNA load and has no significant correlation with ALT.RRM2 might be used as a target for the development of new hepatitis B drugs.