慢性乙型肝炎患者外周血单个核细胞中miR-155和细胞因子信号转导抑制分子1相对表达量与肝功能损伤程度的相关性

Correlation of the expressions of miR-155 and suppressor of cytokine signaling 1 mRNA in peripheral blood mononuclear cells with the degree of liver injury in patients with chronic hepatitis B

目的分析慢性乙型肝炎(chronic hepatitis C,CHB)患者外周血单个核细胞(peripheral blood mononuclear cells,PBMC)中miR-155和细胞因子信号转导抑制分子1(suppressor of cytokine signaling 1,SOCS1)的表达水平,并探讨其与肝功能损伤程度的相关性.方法连续纳入2016年3月至2018年6月于南京中医药大学附属南京医院就诊的95例CHB患者为研究对象(CHB组),根据患者肝组织病理学检查结果分为轻度CHB组(31例)、中度CHB组(38例)和重度CHB组(26例).另选取同期健康体检者50例作为对照组.采用RT-PCR检测受试者外周血PBMC中miR-155和SOCS1 mRNA相对表达量,ELISA法检测CHB患者血清肝功能指标[丙氨酸氨基转移酶(alanine transaminase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)和总胆红素(total bilirubin,TBil)],分析外周血miR-155和SOCS1 mRNA相对表达量与CHB严重程度及肝功能指标的相关性.结果 CHB组患者miR-155相对表达量(0.64±0.15)显著低于对照组(0.86±0.27),SOCS1 mRNA相对表达量(1.25±0.37)显著高于对照组(0.69±0.18),差异均有统计学意义(t=6.314,P<0.001;t=10.081,P<0.001).重度CHB组miR-155相对表达量为0.52±0.13,显著低于中度CHB组(0.65±0.16)和轻度CHB组(0.73±0.20);SOCS1 mRNA相对表达量为1.50±0.25,显著高于中度CHB组(1.21±0.33)和轻度CHB组(1.09±0.31),差异均有统计学意义(P均<0.05).CHB患者miR-155和SOCS1 mRNA表达水平呈显著负相关(r=-0.695,P<0.01).重度CHB组血清ALT、AST、TBil水平分别为(95.97±11.98)U/L、(75.93±10.27)U/L、(22.21±4.09)μmol/L,均显著高于轻度CHB组[(79.73±10.86)U/L、(61.57±9.16)U/L、(18.06±3.14)μmol/L]和中度CHB组[(86.05±12.14)、(66.66±9.38)U/L、(19.73±3.52)μmol/L],差异有统计学意义(P均<0.05),中度CHB组血清ALT、AST、TBil水平与轻度CHB组相比,差异无统计学意义(P均>0.05).CHB患者miR-155相对表达水平与ALT、AST、TBil水平呈负相关(r=-0.457、-0.531、-0.389,P均<0.05),SOCS1 mRNA与ALT、AST、TBil水平呈正相关(r=0.419、0.520、0.371,P均<0.05).结论 CHB患者PBMC中miR-155和SOCS1 mRNA的异常表达与肝功能损伤程度密切相关.

Objective To analyze the expression levels of miR-155 and suppressor of cytokine signaling 1 (SOCS1) mRNA in peripheral blood mononuclear cells (PBMC) of patients with chronic hepatitis B (CHB), and to explore their relationships with the degree of liver injury. Methods A total of 95 patients with CHB in Nanjing Hospital Affiliated to Nanjing University of Traditional Chinese Medicine from March 2016 to June 2018 were continuously enrolled as CHB group. The patients were furtherly divided into mild CHB group (31 cases), moderate CHB group (38 cases) and severe CHB group (26 cases) according to the results of liver histopathology. Another 50 healthy persons were selected as control group during the same period. The relative expressions of miR-155 and SOCS1 mRNA in PBMC were detected by RT-PCR, serum liver function indicators [alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil)] were detected by ELISA. The relationships of the expressions of miR-155 and SOCS1 mRNA in PBMC with the clinical grading and liver function indexes in patients with CHB were analyzed. Results The miR-155 relative expression of patients in CHB group was significantlyo lwer than that in control group [(0.64 ± 0.15)v s (0.86 ± 0.27)], and the relative expression of SOCS1 mRNA was significantly higher than that in control group [(1.25 ± 0.37) vs (0.69 ± 0.18)], the differences were statistically significant (t = 6.314, P < 0.001;t = 10.081, P < 0.001). The miR-155 relative expression of patients in severe CHB group was 0.52 ± 0.13, which was lower than those in moderate CHB group (0.65 ± 0.16) and mild CHB group (0.73 ± 0.20), and the relative expression of SOCS1 mRNA was 1.50 ± 0.25, which was higher than those in moderate CHB group (1.21 ± 0.33) and mild CHB group (1.09 ± 0.31), the differences were statistically significant (P < 0.05). There was a significant negative correlation between the expressions of miR-155 and SOCS1 mRNA in CHB group (r =-0.695, P < 0.01). The levels of serum ALT, AST, and TBil of patients in severe CHB group [(95.97 ± 11.98) U/L,(75.93 ± 10.27) U/L,(22.21 ± 4.09)μmol/L)] were higher than those in mild CHB group [(79.73 ± 10.86) U/L,(61.57 ± 9.16) U/L,(18.06 ± 3.14)μmol/L] and moderate CHB group [(86.05 ± 12.14) U/L,(66.66 ± 9.38) U/L,(19.73 ± 3.52)μmol/L], the differences were statistically significant (P < 0.05);there were no significant differences in serum ALT, AST and TBil levels of patients between moderate CHB group and mild CHB group (P > 0.05). The miR-155 expression level of patients in CHB group was negatively correlated with ALT, AST and TBil levels (r=-0.457,-0.531,-0.389, all P < 0.05), SOCS1 mRNA was positively correlated with ALT, AST, and TBil levels (r = 0.419, 0.520, 0.371, all P < 0.05). Conclusion Abnormal expression of miR-155 and SOCS1 mRNA in PBMC of patients with CHB is closely related to the degree of liver injury.