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NLRP3炎症小体通路参与代谢相关脂肪肝病的发病机制。

NLRP3 inflammasome pathway involved in the pathogenesis of metabolic associated fatty liver disease.

发表日期:2024 Aug 23
作者: Heba Ahmed Osman, Sawsan M A Abuhamdah, Mohammed H Hassan, Abdelkader Ahmed Hashim, Abdelazeem E Ahmed, Sameh Salaheldin Elsayed, Samer A El-Sawy, Mostafa A Gaber, Marwa Abdelhady
来源: TROPICAL MEDICINE & INTERNATIONAL HEALTH

摘要:

代谢相关脂肪肝病 (MAFLD) 的患病率在全球范围内稳步上升,与肥胖和糖尿病的全球流行并行。据估计,全球大约四分之一的人口受到 MAFLD 的影响。尽管 MAFLD 患病率很高,但由于早期缺乏特定症状,MAFLD 经常未被诊断出来。然而,随着疾病的进展,它可能导致更严重的肝脏相关并发症,如纤维化、肝硬化和肝细胞癌。因此,我们的目的是研究核苷酸结合寡聚化结构域、富含亮氨酸重复序列(LRR)的蛋白(NLR)家族含有pyrin结构域的蛋白3 [NLRP3]炎性体途径成分、NLRP3和白细胞介素1β(IL)的表达水平。 -1β) 基因存在于具有不同程度脂肪变性和纤维化的 MAFLD 患者中。参与者被分为两个相等的组; MAFLD组:由120例根据纤维扫描结果显示不同程度肝纤维化和脂肪变性的患者组成。非 MAFLD 组由 107 名参与者组成。使用实时定量聚合酶链反应 (RT-qPCR) 对所有参与者的血液中含有热蛋白结构域的蛋白 3 和 IL-1β 相关基因表达进行分子分析。 MAFLD后肝纤维化患者IL-1β和NLRP3的相对基因表达水平显着升高; IL-1β > 1.1的AUC为0.919,敏感性为88.33,特异性为96.26,PPV为96.4,NPV准确度为88和92.3(p值 < 0.001)。 NLRP3 > 1.33 作为 MAFLD 后肝纤维化的预测因子,其敏感性为 97.5,特异性为 99.07,PPV 为 99.2,NPV 为 97.2,准确度为 98.3,AUC 为 0.991(p 值 < 0.001)。早期纤维化患者 (F0-F1-2) 中 IL-1β 和 NLRP3 的平均相对基因表达水平;分别为31.97±11.8和6.76±2.18;与晚期肝纤维化阶段(F2-F3)的患者相比; 2.62 ± 3.71 和 4.27 ± 2.99(各 p < 0.001)。本研究为 IL-1β 和 NLRP3 炎症小体可能参与代谢相关脂肪肝疾病发病机制提供了新的证据,并且可能成为早期检测 MAFLD 后肝纤维化的有效标志物。© 2024。作者。
The prevalence of Metabolic-associated fatty liver disease (MAFLD) has been steadily increasing worldwide, paralleling the global epidemic of obesity and diabetes. It is estimated that approximately one-quarter of the global population is affected by MAFLD. Despite its high prevalence, MAFLD often goes undiagnosed due to the lack of specific symptoms in its early stages. However, as the disease progresses, it can lead to more severe liver-related complications such as fibrosis, cirrhosis, and hepatocellular carcinoma. Therefore, we aimed to investigate the expression levels of the nucleotide-binding oligomerization domain, leucine-rich repeat (LRR)-containing proteins (NLR) family pyrin domain-containing protein 3 [NLRP3] inflammasome pathway components, NLRP3 and interleukin 1β (IL-1β) genes in patients with MAFLD with various degrees of steatosis and fibrosis. Participants were classified into two equal groups; MAFLD group: consisted of 120 patients with different degrees of hepatic fibrosis and steatosis based on fibro scan results. The non-MAFLD group was comprised of 107 participants. Molecular analysis of pyrin domain-containing protein 3 and IL-1β relative gene expressions was performed in the blood of all participants, using Real-time quantitative polymerase chain reaction (RT-qPCR). Patients with post-MAFLD hepatic fibrosis had significantly higher relative gene expression levels of IL-1β and NLRP3; with IL-1β > 1.1 had AUC of 0.919, sensitivity of 88.33, specificity of 96.26, PPV of 96.4, and NPV of 88 and 92.3 accuracy (p value < 0.001). NLRP3 > 1.33 had a sensitivity of 97.5, specificity of 99.07, PPV of 99.2, NPV of 97.2, and 98.3 accuracy with an AUC of 0.991 (p value < 0.001) as predictors of post-MAFLD hepatic fibrosis.. A significant increase in the mean relative gene expression levels of both IL-1β and NLRP3 found in patients with early fibrosis (F0-F1-2); 31.97 ± 11.8 and 6.76 ± 2.18, respectively; compared with patients with advanced hepatic fibrosis stages (F2-F3); 2.62 ± 3.71 and 4.27 ± 2.99 (p < 0.001 each). The present study provides novel evidence for the possible involvement of IL-1β and NLRP3 inflammasome in metabolic-associated fatty liver disease pathogenesis and could be valid markers for the early detection of post-MAFLD hepatic fibrosis.© 2024. The Author(s).