慢性乙型肝炎肝硬化患者NLRP3及下游因子表达水平和意义  

Expression and Significance of NLRP3 Inflammasome and its Downstream Factors in Patients with Chronic Hepatitis B Liver Cirrhosis

作　　者：李凡 罗薇[2] 白纪红[3] 梁志清[4] 于冰[2] 胡榜利[2] 陆炯敏 付艳君 LI Fan;LUO Wei;BAI Ji-hong;LIANG Zhi-qing;YU Bing;HU Bang-li;LU Jiong -min;FU Yan-jun(Guilin Medical School, Guilin 541000, Guangxi, China)

机构地区：[1]桂林医学院药学院,广西桂林541000 [2]广西医科大学第一附属医院消化科,广西南宁530021 [3]桂林医学院附属医院研究生科,广西桂林541000 [4]桂林医学院附属医院感染科,广西桂林541000

出　　处：《广东医学》2019年第6期782-786,共5页Guangdong Medical Journal

基　　金：国家自然科学基金资助项目(编号:81560103);广西自然科学基金资助项目(编号:2014GXNSFAA118152)

摘　　要：目的检测NLRP3炎症小体及其下游因子ASC、Caspase-1、IL-1β、IL-18表达水平与慢性乙型肝炎肝硬化发生、发展的关系。方法选取慢性乙型肝炎59例、乙型肝炎肝硬化患者57例和健康受试者33例的外周血,并收集慢性乙型肝炎肝硬化肝组织25例,正常对照肝组织9例。采用荧光定量PCR分别检测患者外周血及肝组织NLRP3、ASC、Caspase-1、IL-1β及IL-18 mRNA表达,分析外周血NLRP3炎症小体表达水平与炎症因子之间的关系以及上述指标mRNA表达量与各肝功能生化指标的关系。结果慢性乙型肝炎及乙型肝炎肝硬化外周血中NLRP3、ASC、Caspase-1、IL-1βmRNA的表达量较正常对照组均增高(均P<0.05),而慢性乙型肝炎肝硬化肝组织中NLRP3、ASC、Caspase-1、IL-1βmRNA的表达量较正常对照组均降低(均P<0.05),此外,在外周血与肝组织中IL-18 mRNA的表达量较正常组均增高。结论 NLRP3炎症小体的表达与慢性乙型肝炎肝硬化中炎症活性有关,IL-18可能是预测其预后及评价病情严重程度的重要指标,但其具体机制及可能的信号通路需要进一步研究。Objective To investigate the correlations between the expression of NLRP3 inflammasome and its downstream cytokines, ASC, Caspase-1, IL-1β, IL-18 and the development of chronic hepatitis B cirrhosis. Methods Peripheral blood samples were collected from 59 patients with chronic hepatitis B(CHB), 57 patients with CHB cirrhosis and 33 healthy subjects;while from 25 CHB liver cirrhosis samples, and 9 normal liver tissues were also collected. Expression of NLRP3, ASC, Caspase-1, IL-1β and IL-18 in peripheral blood and liver tissues were detected by real-time quantitative PCR, and the correlations between NLRP3 expression and inflammatory factors in peripheral blood and liver tissues were analyzed. The correlations between mRNA expression levels of NLRP3, ASC, Caspase-1, IL-1β and IL-18 and clinical indicators of CHB and hepatitis B-related cirrhosis were analyzed. Results The expression of NLRP3, ASC, Caspase-1 and IL-1β in peripheral blood of patients with CHB and hepatitis B liver cirrhosis was significantly higher than that in normal control group(all P<0.05). The expression of NLRP3, ASC, Caspase-1, and IL-1β in the liver tissues was significantly lower than that in the normal control group(all P<0.05), while the expression of IL-18 in the peripheral blood and liver tissues was higher than that in the normal group. Conclusion Expression of NLRP3 inflammasome is correlated with the inflammatory activity associated with chronic hepatitis B cirrhosis. IL-18 may be an important index to predict its prognosis and assess the severity of the disease. However, the underlying mechanism and possible signal pathway need further study.

关 键 词：乙型肝炎 肝硬化 NLRP3 IL-1Β IL-18 基因表达 

分 类 号：R512.62[医药卫生—内科学] R575.2[医药卫生—临床医学]