世界中医药

目的：探讨高尿酸血症（HUA）状态下低度炎症的病理特点。方法：根据体质量随机将迪法克鹌鹑分为正常组、模型组，每组10只。以普通饲料：酵母浸膏粉=4:1制备食饵，并以该食饵喂养模型组鹌鹑，正常组鹌鹑则自由饮食饮水。分别于造模第10、20、30天检测血清尿酸，血清炎症介质白细胞介素-1β（IL-1β）、IL-33、IL-2、IL-13、IL-8、IL-17、IL-6、IL-10、IL-12/P40、IL-16、IL-21、C反应蛋白（CRP）、粒细胞巨噬细胞集落刺激因子（GM-CSF）、肿瘤坏死因子-α（TNF-α）、趋化因子CC配体2(CCL2)及γ干扰素（IFN-γ）、神经突起生长导向因子2（Netrin-2）、五聚蛋白3（Pentraxin 3），观察各炎症介质强度变化；造模第30天，取鹌鹑肝、回肠、肾各脏器组织，进行HE染色后观察组织病理形态变化；造模第20天，用基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析差异炎症介质功能及相关信号通路；用Pearson相关性分析方法分析差异炎症介质与血清尿酸水平的相关性。结果：与正常组比较，模型组鹌鹑血清尿酸水平高（P<0.05），以血清IL-17、IL-6、IL-33等为主的白细胞介素类，以IL-8、CCL2为主的趋化因子类，IFN-γ、TNF-α、CRP及GM-CSF水平均升高（P<0.05），而IL-13、IL-10水平降低（P<0.05）。造模第20天，GO/KEGG富集分析结果显示，HUA状态下的低度炎症可能是尿酸代谢靶点群，通过IL-17、Janus激酶信号转导和转录激活因子（JAK-STAT）等信号通路激活、细胞因子-细胞因子间相互作用，从而诱导IL-6、TNF-α等炎症介质产生。2组组织病理变化结果显示，与正常组相比，模型组回肠组织黏膜下层可见炎性细胞浸润，肝、肾组织未见明显差异。差异炎症介质与血清尿酸水平的相关性分析结果显示，鹌鹑血清中IL-6、TNF-α、CRP、IL-33、IL-17、IL-8、IFN-γ、CCL2、GM-CSF、IL-1β、IL-2、IL-6水平均与血清尿酸水平正相关，IL-10、IL-13水平与血清尿酸水平负相关。结论：HUA鹌鹑模型存在低度炎症，该低度炎症可能与尿酸代谢靶点群通过IL-17、JAK-STAT等信号通路的激活以及细胞因子间的相互作用，从而调控IL-6、TNF-α等炎症介质的产生有关。

English Summary:

To investigate the pathological characteristics of low-grade inflammation in hyperuricemia(HUA) conditions.Methods:Defak quails were randomly divided by body weight into a normal group and a model group，with 10 quails in each group.The model group was fed a diet prepared with a ratio of normal feed to yeast extract powder of 4:1，while the normal group had free access to food and water.Serum uric acid and inflammatory mediators，including interleukins-1β(IL-1β)，IL-33，IL-2，IL-13，IL-8，IL-17，IL-6，IL-10，IL-12/P40，IL-16，IL-21，C-reactive protein(CRP)，granulocyte-macrophage colony-stimulating factor(GM-CSF)，tumor necrosis factor-α(TNF-α)，chemokine ligand 2(CCL2)，interferon-γ(IFN-γ)，netrin-2，and pentraxin 3，were measured on the 10th，20th，and 30th days of modeling to observe changes in the intensity of inflammatory mediators.On the 30th day，quail liver，intestine，and kidney tissues were collected for histopathological observation after hematoxylin-eosin(HE) staining.On the 20th day，Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were performed to analyze the functions and related signaling pathways of differential inflammatory mediators.Pearson correlation analysis was used to analyze the correlation between differential inflammatory mediators and serum uric acid levels.Results:Compared with the normal group，the model group had higher serum uric acid levels(P<0.05).Levels of interleukins，predominantly IL-17，IL-6，and IL-33，chemokines，mainly IL-8 and CCL2，and levels of IFN-γ，TNF-α，CRP，and GM-CSF were elevated(P<0.05)，while levels of IL-13 and IL-10 were decreased(P<0.05).On the 20th day of modeling，GO/KEGG enrichment analysis showed that low-grade inflammation in HUA conditions might target uric acid metabolism through activation of IL-17，Janus kinase-signal transducer and activator of transcription(JAK-STAT) signaling pathways，and cytokine-cytokine interactions，thereby inducing the production of inflammatory mediators such as IL-6 and TNF-α.Histopathological analysis showed that，compared with the normal group，the model group exhibited inflammatory cell infiltration in the submucosa of the ileum，with no significant differences observed in liver and kidney tissues.Correlation analysis showed that serum levels of IL-6，TNF-α，CRP，IL-33，IL-17，IL-8，IFN-γ，CCL2，GM-CSF，IL-1β，and IL-2 were positively correlated with serum uric acid levels，while IL-10 and IL-13 levels were negatively correlated with serum uric acid levels.Conclusion:The HUA quail model exhibited low-grade inflammation，which may be related to uric acid metabolism targets through activation of the IL-17 and JAK-STAT signaling pathways and interactions between cytokines，thereby regulating the production of inflammatory mediators such as IL-6 and TNF-α.

查看全文查看/发表评论下载PDF阅读器