慢性乙型病毒性肝炎患者血清中IL-37的水平与HBeAg血清学转换的关系研究

发布时间：2018-07-22 10:47

【摘要】：目的：IL-37是一种新型的抗炎症因子，能限制感染过程中的炎症反应和免疫应答从而避免组织过度损伤。本研究的目的是检测慢性乙型肝炎患者和替比夫定治疗后HBeAg血清学转换患者IL-37的浓度变化，并且与肝功能进行相关性分析，以探讨IL-37在乙肝病毒感染后引起的免疫应答中的作用。方法：分别从40例HBeAg阳性的慢性乙型肝炎（CHB）患者，30例慢性丙型肝炎（CHC）患者，25例丙肝自愈患者（SR-HCV）和30例健康对照者（HC）的静脉中抽取外周血。采用酶联免疫吸附法（ELISA）定量检测各组血清中IL-37的水平。采用微量样本多指标流式蛋白定量法（CBA）检测各组血清中IL-2和IL-10的水平。采用荧光定量PCR方法检测HBV DNA和HCV RNA；采用化学发光分析仪检测HBsAg、HBeAg、HBsAb、HBeAb；采用全自动生化分析仪检测ALT和AST。结果：CHB患者：1、HBeAg阳性的慢性乙肝患者血清中IL-37的浓度显著高于健康对照组（P0.0001）；病毒定量较高的患者血清中IL-37的浓度较高（P0.05），但是IL-37的血清浓度与病毒定量之间没有相关性；2、替比夫定治疗24周和48周后，HBeAg转阴的患者血清中IL-37的浓度较治疗前明显下降（P=0.0146，P0.0001）；但HBeAg转阴患者的HBsAg与治疗前相比没有明显变化；3、ALT、AST异常的患者血清中IL-37的浓度明显高于ALT、AST正常的患者（P0.0001）；4、慢性乙型肝炎患者血清中IL-2和IL-10的浓度明显低于健康对照组（P0.0001）；替比夫定治疗48周后，IL-2的浓度较治疗前显著升高（P0.0001），但IL-10没有明显变化；5、患者血清IL-37的浓度与ALT呈正相关，患者血清IL-2的浓度与AST呈负相关。 CHC患者：1、慢性丙型肝炎和丙肝自愈患者血清中IL-37的浓度与健康对照组相比没有明显变化；2、ALT、AST异常的患者血清中IL-37的浓度明显高于ALT、AST正常的患者（P=0.0379，P=0.0453）；3、慢性丙型肝炎患者血清中IL-2和IL-10的浓度明显低于健康对照组（P0.0001）；丙肝自愈患者血清中IL-2和IL-10的浓度与慢性丙型肝炎患者相比没有明显变化。结论：1、HBV的感染过程可能上调了IL-37的表达，替比夫定抑制病毒复制的同时影响了IL-37的表达；2、替比夫定治疗后，，IL-37可能参与了HBeAg血清学转换介导的免疫反应。3、IL-37的水平可能反映了肝脏炎症损伤的程度。4、未来IL-37可能成为HBV感染治疗的一种有效手段。
[Abstract]:Objective\ The aim of this study was to detect the concentration of IL-37 in patients with chronic hepatitis B and in patients with HBeAg serological conversion after tibivudine treatment, and to analyze the correlation between IL-37 and liver function. To explore the role of IL-37 in the immune response after hepatitis B virus infection. Methods: peripheral blood was extracted from 40 patients with HBeAg positive chronic hepatitis B (CHB), 30 patients with chronic hepatitis C (CHC) and 25 patients with self-healing hepatitis C (SR-HCV) and 30 healthy controls (HC). The level of IL-37 in serum of each group was determined by Elisa. The levels of IL-2 and IL-10 in serum of each group were detected by flow protein quantitative assay (CBA). HBV DNA and HCV RNAs were detected by fluorescence quantitative PCR, HBeAg HBeAbs HBeAb HBeAbHBeAbs by chemiluminescence analyzer, alt and ASTby automatic biochemical analyzer. Results the serum levels of IL-37 in patients with 1: 1 + HBeAg were significantly higher than those in healthy controls (P0.0001), but the serum levels of IL-37 were higher in patients with higher viral quantification (P0.05), but there was no correlation between the serum concentrations of IL-37 and viral quantification. (2) after 24 weeks and 48 weeks of tibivudine treatment, the concentration of IL-37 in the serum of patients with HBeAg turned negative was significantly lower than that before treatment (P0. 0146, P0. 0001), but there was no significant change in HBsAg in patients with HBeAg turning to negative after treatment. 3The levels of IL-37 in serum of patients with abnormal alt were significantly higher than those of patients with normal alt (P0.0001) and the levels of IL-2 and IL-10 in patients with chronic hepatitis B were significantly lower than those in healthy controls (P0.0001). After 48 weeks of tibivudine treatment, the level of IL-2 was significantly higher than that before treatment (P0.0001), but IL-10 did not change significantly. The serum level of IL-37 was positively correlated with alt. The concentration of IL-2 in serum was negatively correlated with AST in CHC patients. The serum levels of IL-37 in patients with chronic hepatitis C and self-healing of hepatitis C were not significantly different from those in healthy controls. 2the level of IL-37 in serum of patients with abnormal alt was significantly higher than that of patients with normal alt (P0. 0379, P0. 0453). The serum levels of IL-2 and IL-10 in patients with chronic hepatitis C were significantly lower than those in healthy controls (P0. 0001). The levels of IL-2 and IL-10 in serum of patients with chronic hepatitis C did not change significantly compared with those of patients with chronic hepatitis C. Conclusion the expression of IL-37 may be upregulated in the process of infection with HBV. Tibivudine inhibits the replication of the virus and affects the expression of IL-37. After tibivudine treatment, IL-37 may be involved in the immune response mediated by serological transformation of HBeAg. The level of IL-37 may reflect the degree of liver inflammation injury. IL-37 may become an effective method for the treatment of HBV infection in the future.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R512.62

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