慢性乙型肝炎患者外周血单个核细胞中凋亡分子表达水平及临床意义

Expression level and clinical significance of apoptosis molecules in peripheral blood mononuclear cells of patients with chronic hepatitis B

目的探讨慢性乙型肝炎(CHB)患者外周血单个核细胞(PBMC)中凋亡分子表达水平及临床意义。方法以2018年1月至2020年7月郑州市某医院消化内科诊治的CHB患者为研究对象,比较不同病情程度患者PBMC中凋亡分子(Caspase-3、Caspase-6、Caspase-8)mRNA表达量、辅助T细胞(Th)1细胞因子[白细胞介素(IL)-2、干扰素γ(IFN-γ)]、Th2细胞因子(IL-4、IL-10)水平,采用Pearson相关性分析凋亡分子与IL-2/IL-10、IFN-γ/IL-4的相关性。根据凋亡分子表达均数分为低表达者、高表达者,比较不同表达CHB患者HBV-DNA载量,并分析凋亡分子与乙型肝炎病毒(HBV)-DNA的关系。结果本研究共纳入CHB患者116例,男83例,占71.6%。患者年龄27~78岁,以45~59岁所占比例最大,占50.9%。轻、中、重度患者分别为36、45、35例,分别占31.0%、38.8%、30.1%。不同病情程度的CHB患者PBMC中Caspase-3 mRNA、Caspase-6 m RNA、Caspase-8 mRNA表达量差异均有统计学意义(均P<0.01)。重度患者IL-2、IFN-γ、IL-2/IL-10、IFN-γ/IL-4低于中度、轻度患者,IL-4、IL-10高于中度、轻度患者(均P<0.01)。以HBV-DNA载量1×10^(5)copy/mL为界分为高载量与低载量,HBV-DNA高载量患者PBMC中Caspase-3 mRNA、Caspase-6 mRNA、Caspase-8 m RNA表达量高于HBV-DNA低载量患者(P<0.01);且3者mRNA与IL-2/IL-10、IFN-γ/IL-4呈负相关(P<0.05),与HBV-DNA载量呈正相关(P<0.05)。结论 PBMC中凋亡分子(Caspase-3、Caspase-6、Caspase-8)mRNA表达随CHB患者病情加重而升高,并与Th1/Th2失衡及HBV-DNA载量具有相关性,抑制凋亡分子表达可为Th1/Th2失衡的纠正及控制HBV的复制提供新思路。

Objective To explore the expression level and clinical significance of apoptosis molecules in peripheral blood mononuclear cells(PBMC)of patients with chronic hepatitis B(CHB).Methods Taking CHB patients diagnosed and treated in the department of gastroenterology of a hospital in Zhengzhou from January 2018 to July 2020 as the research object,comparing the mRNA expression of apoptosis molecules(including Caspase-3,Caspase-6,Caspase-8)in PBMC,T Helper(Th)1 cytokine levels[including interleukin(IL)-2 and interferon-γ(IFN-γ)],and Th2 cytokine levels(including IL-4 and IL-10)among patients with different severity degree. Pearson correlation analysis method was used to analyze the relationship of apoptosis molecules to IL-2/IL-10 and IFN-γ/IL-4. According to the average expression of apoptotic molecules,the patients were divided into low expression and high expression to compare the hepatitis B virus(HBV)-DNA load,and the relationship between apoptotic molecules and HBV-DNA was analyzed.Results A total of 116 patients with CHB were included in this study,including 83 males,accounting for 71.6%. The age of the patients was 27-78 years old,with the largest proportion of 45-59 years old,accounting for 50.9%. There were 36,45 and 35 patients with mild,moderate and severe CHB,accounting for 31.0%,38.8% and 30.1% respectively. The expression levels of Caspase-3 mRNA,Caspase-6 m RNA,and Caspase-8 mRNA in PBMC of CHB patients with different severity degree were significantly different(all P<0.01). IL-2,IFN-γ,IL-2/IL-10,and IFN-γ/IL-4 in severe patients were lower than moderate and mild patients,IL-4 and IL-10 were higher than moderate and mild patients(all P<0.01). The HBVDNA load was equal to 1×10^(5) copy/mL as the boundary,Caspase-3 mRNA,Caspase-6 mRNA,and Caspase-8 mRNA in PBMC of patients with high HBV-DNA load were higher than those of patients with low HBV-DNA load(P<0.05). Caspase-3 mRNA,Caspase-6 mRNA,and Caspase-8 mRNA was negatively correlated with IL-2/IL-10 and IFN-γ/IL-4(P<0.05),and positively correlated with HBV-DNA load(P<0.05).Conclusion The expression of apoptotic molecules mRNA(including Caspase-3,Caspase-6,Caspase-8)in PBMC go up with the progression of CHB patients,and it has a correlation with Th1/Th2 imbalance and HBV-DNA load,inhibiting the expression of apoptotic molecules can provide a potential idea for correcting Th1/Th2 imbalance and controlling HBV replication.