酒精性肝病患者肝组织NLRP3炎症复合体基因水平检测及其意义

Role of nucleotide-binding and oligomerization domain-like receptors P3 inflammasome in patients with alcoholic liver diseases

目的探讨核苷酸结合性寡聚区蛋白样受体(NLR)P3炎症复合体在酒精性肝病(ALD)发病中的作用。方法本研究获得酒精性肝炎(AH)12例、酒精性肝硬化(ALC)4例和健康人(HC)12例肝组织,采用RT-PCR法检测肝组织NLRP3、Caspase-1和IL-1βm RNA水平。采集ALD患者84例【AH20例、ALC48例(Child-Pugh A级19例、B级22例和C级7例)和重症酒精性肝炎(SAH)16例】和健康人40例血浆,采用ELISA法检测血浆IL-1β水平,采用Spearman秩相关分析血浆IL-1β水平与临床检验指标的相关性。结果 AH和ALC患者肝组织NLRP3 m RNA水平分别为(28.1±2.8)和(28.4±3.1),均显著高于HC组【(8.8±1.8),P<0.001】,Caspase-1m RNA水平分别为(18.8±1.2)和(24.6±1.8),均显著高于HC组【(15.1±1.0),P<0.05】,IL-1βm RNA水平分别为(17.0±2.9)和(16.3±4.4),均显著高于HC组【(7.0±1.1),P<0.01】;肝组织NLRP3 m RNA水平分别与IL-1βm RNA或Caspase-1 m RNA水平呈正相关(P<0.05);AH、ALC和SAH患者血浆IL-1β水平分别为(36.1±1.8)pg/m L、(28.0±1.6)pg/m L和(32.5±2.4)pg/m L,均显著高于HC组【(14.7±0.8)pg/m L,P<0.01】;不同Child-Pugh分级ALC患者IL-1β水平无显著性差异(P>0.05);ALD患者血浆IL-1β水平与ALT和AST/ALT比值呈正相关。结论 NLRP3炎症复合体主要组分及促炎细胞因子IL-1β在ALD患者肝组织和血浆水平升高,可能参与了ALD发病的炎症反应过程。

Objective To explore the role of nucleotide-binding and oligomerization domain-like receptors （NLR） P3 inflammasome in patients with alcoholic liver diseases （ALD）. Methods The liver tissues from 12 patients with alcoholic hepatitis （AH）,4 with alcoholic liver cirrhosis （ALC） and 12 healthy persons were obtained in this study,and NLRP3,Caspase 1 and IL-1 beta mRNA levels were detected by RT-PCR. Plasma IL-1β levels were assayed by ELISA in 84 patients with ALD [20 with AH,48 with ALC （19 with Child-Pugh class A,22 with class B and 7 with class C）,16 with severe alcoholic hepatitis （SAH） and 40 healthy persons. The correlation of plasma IL-1 β level to biochemical indexes was analyzed. Results The hepatic NLRP3 mRNA levels in patients with AH and ALC were （28.1±2.8） and （28.4±3.1）,significantly higher than that in healthy control [（8.8±1.8）,P〈0.01],the Caspase-1 mRNA levels were（18.8±1.2） and （24.6±1.8）,significantly higher than that in healthy persons [（15.1±1）,P〈0.05],IL-1β mRNA levels were （17.0±2.9） and （16.3±4.4）,significantly higher than that in healthy control [（7.0±1.1）,P〈0.01],and NLRP3 mRNA levels was positively correlated to IL-1β mRNA or Caspase 1 mRNA（P〈0.05）;plasma IL-1β levels in patients with AH,ALC and SAH were（36.1±1.8） pg/mL,（28.0 ±1.6） pg/ml and （32.5 ±2.4） pg/ml, respectively,significantly higher than that in healthy persons [（1.5±0.8） pg/ml,P〈0.01];the plasma IL-1βlevels in patients with Child-Pugh class A,B and C had no significant difference （P〉0.05）;plasma IL-1βlevel in patients with ALD was positively correlated to serum ALT or the ratio of AST/ALT. Conclusion NLRP3 inflammasome and proinflammatory cytokinesIL-1β are involved in patients with ALD,and they might play an important roles in liver inflammatory process.