NASH患者外周血单个核细胞TXNIP/NLRP3水平变化及其临床意义探讨

Implications of peripheral blood mononuclear lymphocyte TXNIP/NLRP3 in patients with nonalcoholic steatohepatitis

目的探讨非酒精性脂肪性肝炎(NASH)患者外周血单个核细胞(PBMCs)硫氧还蛋白互作蛋白(TXNIP)/NOD样受体家族含pyrin结构域蛋白3(NLRP3)水平变化及其临床意义。方法2019年1月~2021年1月我院收治的150例NASH患者和同期体检的单纯性脂肪肝患者45例,取外周血分离PBMCs,并检测TXNIP/NLRP3 mRNA。对NASH患者行两次肝穿刺活检,将肝组织病变程度分为轻度、中度和重度及进展和无进展组。结果NASH患者血清ALT和AST水平分别为(72.2±6.9)U/L和(61.8±5.1)U/L,显著高于单纯性脂肪肝组【分别为(33.4±4.0)U/L和(31.3±3.1)U/L,P<0.05】;NASH组PBMCs TXNIP mRNA、NLRP3 mRNA和TXNIP/NLRP3比值分别为(1.9±0.1)、(1.5±0.1)和(1.3±0.1),显著高于单纯性脂肪肝组【分别为(0.7±0.1)、(0.6±0.1)和(1.1±0.1),P<0.05】;33例重度NASH组PBMCs TXNIP mRNA、NLRP3 mRNA和TXNIP/NLRP3比值分别为(2.4±0.2)、(1.9±0.2)和(1.6±0.1),显著高于49例轻度组【分别为(1.5±0.1)、(1.2±0.1)和(1.0±0.1),P<0.05】或68例中度组【分别为(2.0±0.2)、(1.5±0.1)和(1.4±0.1),P<0.05】;31例进展期NASH组PBMCs TXNIP mRNA、NLRP3 mRNA和TXNIP/NLRP3比值分别为(2.1±0.2)、(1.7±0.2)和(1.5±0.1),显著高于119例无进展组【分别为(1.8±0.1)、(1.4±0.1)和(1.2±0.1),P<0.05】。结论NASH患者PBMCs TXNIP/NLRP3基因水平显著升高,与肝功能损害程度明显存在某种关系。积极监测患者PBMCs这些基因的动态变化可能对评估病情和疾病转归有重要的意义,值得深入研究。

Objective The aim of this study was to explore the implications of peripheral blood mononuclear lymphocyte(PBMC)thioredoxin-interacting protein(TXNIP)/nod-like receptor family pyrin domain-containing protein 3(NLRP3)in patients with nonalcoholic steatohepatitis(NASH).Methods A total of 150 patients with NASH and 45 persons with simple fatty liver(SFL)were recruited in our hospital between January 2019 and January 2021,and all had their PBMCs being separated to detect the TXNIP/NLRP3 mRNA.All patients with NASH had liver biopsies at presentation for determination of liver tissues injury degrees as mild,moderate and severe,and had a second time liver biopsies a year after recruitment as for determination of progressive or non-progressive diseases.Results Serum ALT and AST levels in patients with NASH were(72.2±6.9)U/L and(61.8±5.1)U/L,both significantly higher than[(33.4±4.0)U/L and(31.3±3.1)U/L,respectively,P<0.05]in patients with SFL;the PBMCs TXNIP mRNA,NLRP3 mRNA and the ratio of TXNIP/NLRP3 in patients with NASH were(1.9±0.1),(1.5±0.1)and(1.3±0.1),all significantly higher than[(0.7±0.1),(0.6±0.1)and(1.1±0.1),respectively,P<0.05]in patients with SFL;the PBMCs TXNIP mRNA,NLRP3 mRNA and the ratio of TXNIP/NLRP3 in 33 patients with severe NASH were(2.4±0.2),(1.9±0.2)and(1.6±0.1),significantly higher than[(1.5±0.1),(1.2±0.1)and(1.0±0.1),respectively,P<0.05]in 49 patients with mild NASH or[(2.0±0.2),(1.5±0.1)and(1.4±0.1),respectively,P<0.05]in 68 patients with moderate NASH;the PBMCs TXNIP mRNA,NLRP3 mRNA and the ratio of TXNIP/NLRP3 in 31 patients with progressive NASH were(2.1±0.2),(1.7±0.2)and(1.5±0.1),all significantly higher than[(1.8±0.1),(1.4±0.1)and(1.2±0.1),respectively,P<0.05]in 119 patients without progressive NASH.Conclusion The PBMC TXNIP/NLRP3 mRNA in patients with NASH significantly increase,seemingly have some correlation to the liver tissue injuries,and needs further investigation.