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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
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。
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.
炎症性肠病 / NLRP1 / NLRP3 / 炎性体 / 信号通路 / 免疫机制 / 儿童
Inflammatory bowel disease / Nucleotide-binding oligomerization domain-like receptor protein 1 / Nucleotide-binding oligomerization domain-like receptor protein 3 / Inflammasome / Signaling pathway / Immune mechanism / Child
[1] Dibley L, Bager P, Czuber-Dochan W, et al. Identification of research priorities for inflammatory bowel disease nursing in Europe:a Nurses-European Crohn's and Colitis Organisation Delphi survey[J]. J Crohns Colitis, 2017, 11(3):353-359.
[2] Mählmann L, Gerber M, Furlano RI, et al. Psychological wellbeing and physical activity in children and adolescents with inflammatory bowel disease compared to healthy controls[J]. BMC Gastroenterol, 2017, 17(1):160.
[3] 田佳雯. 固有免疫细胞在炎症性肠病发病机制中的作用[J]. 国际儿科学杂志, 2018, 45(5):357-360.
[4] Gonçalves P, Araújo JR, Di Santo JP. A cross-talk between microbiota-derived short-chain fatty acids and the host mucosal immune system regulates intestinal homeostasis and inflammatory bowel disease[J]. Inflamm Bowel Dis, 2018, 24(3):558-572.
[5] 任改艳, 黄剑林. NLRP3炎症小体与炎症性肠病的研究进展[J]. 中国免疫学杂志, 2019, 35(13):1662-1665.
[6] 中华医学会消化病学分会炎症性肠病学组. 炎症性肠病诊断与治疗的共识意见(2012年·广州)[J]. 胃肠病学, 2012, 17(12):763-781.
[7] 沈玲燕, 杜娟, 张冰凌, 等. 不同胶囊内镜评分指数评估克罗恩病活动程度的相关性分析[J]. 中华消化杂志, 2015, 35(10):654-658.
[8] 杨晓燕, 周丽莎, 董帜, 等. 活动期溃疡性结肠炎MSCT表现与Mayo评分的相关性[J]. 临床放射学杂志, 2015, 34(10):1594-1597.
[9] Holtman GA, Lisman-van Leeuwen Y, Day AS, et al. Use of laboratory markers in addition to symptoms for diagnosis of inflammatory bowel disease in children:a meta-analysis of individual patient data[J]. JAMA Pediatr, 2017, 171(10):984-991.
[10] 姚佳伟, 李晓露, 邵佩, 等. 儿童炎症性肠病病因及发病机制研究进展[J]. 中国实用儿科杂志, 2019, 34(6):517-522.
[11] Zeissig S, Rosati E, Dowds CM, et al. Vedolizumab is associated with changes in innate rather than adaptive immunity in patients with inflammatory bowel disease[J]. Gut, 2019, 68(1):25-39.
[12] 李艳蝶, 卢美萍. NLRP3炎症小体与儿童自身炎症性疾病研究进展[J]. 浙江大学学报(医学版), 2017, 46(4):449-453.
[13] 张目涵, 周力为, 贺欣, 等. IL-27在小鼠结肠炎中的作用及对NLRP3炎性小体的影响[J]. 中国病理生理杂志, 2018, 34(6):1089-1094.
[14] 李展. NLRP3炎性小体在炎症性肠病患者肠组织中的表达及意义[D]. 郑州:郑州大学, 2016.
[15] 郭庆玲. 炎症小体在自身免疫甲状腺炎发病机制中的作用及机制研究[D]. 沈阳:中国医科大学, 2018.
[16] 高永利, 叶明, 高乐, 等. 肠黏膜核苷酸结合寡聚化结构域样受体-3炎症小体在肠炎组织中的表达及意义[J]. 临床和实验医学杂志, 2017, 16(22):2218-2221.
[17] 郑沁薇, 郝微微, 王凯强, 等. NLRP3炎症小体对炎症性肠病免疫机制影响的研究进展[J]. 世界华人消化杂志, 2019, 27(6):389-394.
[18] Swaroop S, Mahadevan A, Shankar SK, et al. Correction to:HSP60 critically regulates endogenous IL-1β production in activated microglia by stimulating NLRP3 inflammasome pathway[J]. J Neuroinflammation, 2018, 15(1):317.
