NLRP1、NLRP3炎性体信号通路在儿童炎症性肠病免疫机制中的作用研究

Role of NLRP1 and NLRP3 inflammasome signaling pathways in the immune mechanism of inflammatory bowel disease in children

摘要:

目的 探究核苷酸结合寡聚化结构域样受体-3（NLRP3）、核苷酸结合寡聚化结构域样受体-1（NLRP1）炎性体信号通路在儿童炎症性肠病（IBD）免疫机制中的作用。方法 选取126例IBD患儿作为研究组，根据疾病类型分为克罗恩病（CD）（n=32）、溃疡性结肠炎（UC）（n=94）亚组；选取同期行结肠切除手术的结肠息肉/先天性巨结肠患儿120例作为对照组。比较各组肠黏膜NLRP3 mRNA、NLRP1 mRNA、Caspase-1 mRNA、IL-1β mRNA表达情况。结果 研究组NLRP3 mRNA、NLRP1 mRNA、Caspase-1 mRNA、IL-1β mRNA水平高于对照组，随CD、UC病情严重程度增加呈升高趋势（均P < 0.05）；UC、CD组患儿NLRP3 mRNA、NLRP1 mRNA、Caspase-1 mRNA、IL-1β mRNA均与血清IgM、IgG呈正相关（均P < 0.05），NLRP3 mRNA、NLRP1 mRNA均与Caspase-1 mRNA、IL-1β mRNA呈正相关（均P < 0.05）。结论 NLRP3、NLRP1炎性体信号通路可能通过上调Caspase-1、IL-1β表达参与儿童IBD的免疫机制调节。

Abstract:

Objective To study the role of nucleotide-binding oligomerization domain-like receptor proteins 1 and 3 (NLRP1 and NLRP3) inflammasome signaling pathways in the immune mechanism of inflammatory bowel disease (IBD) in children. Methods A total of 126 children with IBD were enrolled as the study group, including 32 children with Crohn's disease (CD) and 94 children with ulcerative colitis (UC). A total of 120 children who underwent colectomy were enrolled as the control group. The mRNA expression of NLRP1, NLRP3, Caspase-1, and interleukin-1β (IL-1β) was compared between groups. Results The study group had significantly higher mRNA expression of NLRP1, NLRP3, Caspase-1, and IL-1β than the control group, and their mRNA expression levels tended to increase with the severity of CD or UC (P < 0.05). In the children with UC or CD, the mRNA expression levels of NLRP1, NLRP3, Caspase-1, and IL-1β were positively correlated with serum IgM and IgG levels (P < 0.05), and the mRNA expression levels of NLRP1 and NLRP3 were positively correlated with those of Caspase-1 and IL-1β (P < 0.05). Conclusions The NLRP1 and NLRP3 inflammasome signaling pathways may regulate the immune mechanism of IBD in children by upregulating the expression of Caspase-1 and IL-1β.