白介素-8在乙肝相关性慢加急性肝衰竭中水平及意义

发布时间：2018-03-18 05:06

本文选题：白细胞介素-8　切入点：乙型肝炎病毒　出处：《安徽医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的探讨白细胞介素8(Interleukin,IL-8)在乙型肝炎相关性慢加急性肝功能衰竭(HBV-acute-on-chronic liver failure,HBV-ACLF)患者中的水平变化及临床价值。方法对62例HBV-ACLF患者和57例HBV患者采用免疫组化技术分析肝组织IL-8水平与分布情况,利用ELISA技术测定血清IL-8水平。同时测定HBV-DNA和肝功能指标,如血清丙氨酸氨基转移酶(Alanine aminotransferase,ALT)、碱性磷酸酶(Alkaline phosphatase,ALP)、天门冬氨酸氨基转移酶(Aspartate transaminase,AST)、总胆红素和肌酐等。按照HBV-ACLF组患者的临床转归情况,将HBV-ACLF组分为好转组和死亡组,计算MELD评分。以Ficoll密度梯度离心法分离HBV-ACLF患者外周血中外周血单个核细胞(Peripheral blood mononuclear cells,PBMCs)并分为四组,分别为空白对照、IL-8组、α-干扰素(Alpha-interferon,IFN-α)组和IL-8+IFN-α联合处理组。经过6h处理作用后,收集细胞蛋白,通过RT-q PCR、Western Blot技术检测JAK-STAT信号途径中主要分子及蛋白的表达。结果肝组织或外周血中,HBV-ACLF患者的IL-8含量高于HBV患者,同时显著高于对照组;且经Pearson相关性分析,HBV500 IU/ml时血清IL-8与HBV-DNA水平呈正相关(r=0.416,P0.05)。与HBV患者和对照组相比,HBV-ACLF患者血清中ALT,AST,ALP,总胆红素和肌酐含量均有明显增加。血清中IL-8含量与ALT和AST有显著的正相关性(r=0.216,P0.05;r=0.317,P0.05)。按照HBV-ACLF组患者的临床转归情况,将HBV-ACLF组分为好转组和死亡组,死亡组患者的IL-8含量显著高于好转组,差异具有统计学意义(P0.05)。且HBV-ACLF患者的血清IL-8含量与MELD评分呈显著正相关(r=0.313,P0.05)。四组HBV-ACLF患者的PBMCs中IFN-α处理组STAT1、STAT2、IRF9等相关信号转导分子及抗病毒蛋白Mx A的表达最高(P0.05),IL-8与IFN-α联合处理组的信号分子及蛋白表达最低(P0.05)。与空白对照组相比,IL-8处理组表达水平显著降低(P0.05),提示IL-8可能通过某些机制影响JAK-STAT信号转导通路,从而对抗病毒。蛋白的表达有一定的抑制作用。IL-8与IFN-α联合处理组的信号分子及蛋白表达明显低于IFN-α处理组(P0.05),说明当IL-8存在时,IFN-α的抗病毒表达明显受到了抑制,从而提示IL-8可能对IFN-α的抗病毒效应有一定的负向调节作用。结论HBV-ACLF患者的肝组织及血清IL-8水平与慢性乙肝患者组和健康对照组相比,均有明显的升高,且血清IL-8水平与其肝脏炎症损伤程度具有相关性。IL-8对HBV-ACLF患者的外周血单个核细胞内JAK-STAT途径分子和Mx A等抗病毒蛋白的表达有一定的抑制作用,并对IFN-α的抗病毒效应具有一定的负向调节作用。
[Abstract]:Objective to investigate the level and clinical value of interleukin 8 (IL-8) in patients with chronic hepatitis B associated with chronic liver failure and acute hepatic failure. Methods 62 patients with HBV-ACLF and 57 patients with HBV were analyzed by immunohistochemical technique. The level and distribution of weaving IL-8, Serum IL-8, HBV-DNA and liver function were measured by ELISA technique. For example, serum alanine aminotransferase, alkaline phosphatase, aspartate transaminase, total bilirubin and creatinine. According to the clinical outcome of patients with HBV-ACLF, the HBV-ACLF group was divided into improvement group and death group. MELD score was calculated. Peripheral blood mononuclear cells were isolated from peripheral blood of patients with HBV-ACLF by Ficoll density gradient centrifugation. They were divided into four groups: blank control group (IL-8), 伪 -interferon Alpha-interferon IFN- 伪 (IFN- 伪) group and IL-8 IFN- 伪 combined treatment group. The expression of major molecules and proteins in JAK-STAT signaling pathway was detected by RT-q PCR Western Blot. Results the IL-8 content of HBV-ACLF patients in liver tissue or peripheral blood was higher than that in HBV patients and significantly higher than that in control group. After Pearson correlation analysis, the serum IL-8 and HBV-DNA levels were positively correlated with those of HBV patients and controls. Compared with HBV patients and control group, serum alt, total bilirubin and creatinine levels in HBV-ACLF patients were significantly increased, and IL-8 levels were significantly higher than those in ALT and AST patients. There was a positive correlation between 0.216m and 0.216p 0.05. According to the clinical outcome of patients in HBV-ACLF group, The HBV-ACLF group was divided into improved group and death group. The IL-8 content in the dead group was significantly higher than that in the improved group. The difference was statistically significant (P 0.05). There was a significant positive correlation between serum IL-8 content and MELD score in patients with HBV-ACLF. The highest expression of IL-8 and IFN- 伪 related signal transduction molecules, such as STAT1, STAT2, IRF9, and anti-virus protein MxA, were observed in PBMCs of four groups of HBV-ACLF patients. Compared with the control group, the level of signal molecule and protein expression in the combined treatment group was significantly lower than that in the control group, suggesting that IL-8 might affect the JAK-STAT signal transduction pathway through some mechanisms. The expression of signal molecules and proteins in IL-8 and IFN- 伪 treated group was significantly lower than that in IFN- 伪 treatment group (P 0.05), which indicated that the antiviral expression of IFN- 伪 was significantly inhibited when IL-8 was present. Conclusion the level of IL-8 in liver and serum of HBV-ACLF patients is significantly higher than that of chronic hepatitis B patients and healthy controls. The level of serum IL-8 was correlated with the degree of liver inflammation. IL-8 could inhibit the expression of JAK-STAT pathway molecules and MxA antiviral proteins in peripheral blood mononuclear cells (PBMC) of HBV-ACLF patients. And the antiviral effect of IFN- 伪 was negatively regulated.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R512.62;R575.3

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