慢性乙型肝炎感染患者血清CTGF表达及与肝纤维化、Th17/Treg平衡的关系

The expression of serum CTGF and its relationships with liver fibrosis and Th17/Treg balance in patients with chronic hepatitis B infection

目的 检测慢性乙型肝炎(CHB)感染患者血清结缔组织生长因子(CTGF)的水平变化,并分析其与肝纤维化、Th17/Treg平衡的关系。方法 收集2016年6月至2018年6月该院确诊的CHB患者146例(研究组),同期来院体检者90例(对照组)作为研究对象,采集研究对象空腹静脉血,检测丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TB)水平,采用酶联免疫吸附法(ELISA)检测血清CTGF、白细胞介素-17(IL-17)水平,流式细胞仪检测辅助性T淋巴细胞17(Th17)、调节性T淋巴细胞(Treg)百分率。分析CTGF与Th17/Treg的相关性及其与肝功能指标的相关性,受试者工作特征曲线(ROC曲线)分析CTGF、Th17/Treg对CHB诊断价值。结果 研究组血清中肝功能指标ALT、AST、TB均高于对照组,差异有统计学意义( P <0.05);血清CTGF、IL-17水平、Th17百分率、Th17/Treg比值高于对照组( P <0.05),Treg百分率与对照组比较差异无统计学意义( P >0.05);随患者肝纤维化程度加深,血清CTGF、IL-17及Th17、Th17/Treg均显著升高( P <0.05),Treg百分率呈现下降的趋势( P <0.05)。Pearson相关性分析结果显示,CHB患者血清CTGF与Th17/Treg、IL-17、Th17呈正相关( r =0.670,0.603、0.618, P =0.000);Th17/Treg与IL-17、Th17呈正相关( r =0.703、0.645, P =0.000);Treg与CTGF、IL-17、Th17、Th17/Treg呈负相关( r =-0.609、-0.598、-0.624、-0.683, P =0.000)。CTGF、Th17/Treg的ROC曲线下的面积(AUC)分别为 0.695 、0.753,灵敏度分别为68.9%、77.8%,特异度分别为56.7%、67.8%。结论 血清CTGF、Th17/Treg比值异常升高与CHB密切相关,检测CTGF、Th17/Treg可间接判断患者病情发展,并且为疾病的治疗提供理论基础。

Objective To detect the level change of serum connective tissue growth factor (CTGF) in patients with chronic hepatitis B infection,and to analyze its relationships with liver fibrosis and Th17/Treg balance. Methods 146 patients with chronic hepatitis B (CHB) diagnosed(research group) in a hospital from June 2016 to June 2018 were collected,and 90 cases came to the hospital for physical examination(control group) as subjects,fasting venous blood was collected,the levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST) and total bilirubin (TB) were detected by the automatic biochemical analyzer,ELISA was used to detect serum CTGF,interleukin-17 (IL-17),the expressions of helper T lymphocyte 17 (Th17) and regulatory T lymphocyte (Treg) were detected by flow cytometry,and the ratio of Th17 to Treg was analyzed.Compared the correlations between CTGF,Th17/Treg with the detection index,and the correlation between CTGF with Th17/Treg,and analyzed the diagnostic values of CTGF and Th17/Treg by receiver operating characteristic curve (ROC curve). Results The serum ALT,AST and TB of the research group were higher than those of the control group,the difference was statistically significant ( P <0.05);Serum levels of CTGF,IL-17 and Th17,Th17/Treg were higher than those of the control group ( P <0.05),There was no significant difference in the expression rate of Treg between research group and control group ( P >0.05).The levels of CTGF,IL-17,Th17 and Th17/Treg in serum increased with the degree of liver fibrosis ( P <0.05),and the expression of Treg decreased ( P <0.05).Pearson correlation analysis showed that serum CTGF was positively correlated with Th17/Treg,IL-17 and Th17 ( r =0.670,0.603,0.618, P =0.000),Th17/Treg was positively correlated with IL-17 and Th17 ( r =0.703,0.645, P =0.000),Treg was negatively correlated with CTGF,IL-17,Th17 and Th17/Treg ( r =-0.609,-0.598,-0.624,-0.683, P =0.000).ROC analysis showed that the AUC area of CTGF and Th17/Treg were 0.695 and 0.753,the sensitivity were 68.9% and 77.8% respectively,and the specificity were 56.7% and 67.8% respectively. Conclusion The abnormal increases of serum CTGF and Th17/Treg ratio are closely related to chronic hepatitis B,detection of CTGF and Th17/Treg can indirectly judge the development of the disease,and provide a theoretical basis for the treatment of the disease.