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研究益生菌和益生元通过调节 TLR4/NF-kB 信号通路对卵清蛋白-脂多糖诱导的过敏性哮喘炎症和肺炎的治疗作用。

Study effect of probiotics and prebiotics on treatment of OVA-LPS-induced of allergic asthma inflammation and pneumonia by regulating the TLR4/NF-kB signaling pathway.

机构信息

General Internal Medicine Ward, Zhengzhou Central Hospital Affiliated To Zhengzhou University, Zhengzhou City, 450007, China.

Department of Cardiology, School of Medicine, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

J Transl Med. 2022 Mar 16;20(1):130. doi: 10.1186/s12967-022-03337-3.

Abstract

Asthma is a common respiratory disease, and immune system dysregulation has direct relevance to asthma pathogenesis. Probiotics and prebiotics have immunomodulatory effects and can regulate immune responses and may attenuate allergic reactions. Therefore, in this study, we explored the role of probiotics and prebiotics in regulating acute airway inflammation and the TLR4/NF-kB pathway. Allergic asthma model of BALB/c mice was produced and treated with probiotics (LA-5, GG, and BB-12) and prebiotics (FOS and GOS). Then AHR, BALF cells count, EPO activity, IL-4, 5, 13, 17, 25, 33, as well as IFN-γ, total and OVA-specific IgE, IgG1, Cys-LT, LTB4, LTC4, and TSLP levels were measured. Also, the GTP/GOT assay was performed and gene expression of Akt, NLR3, NF-kB, PI3K, MyD88, TLR4, CCL11, CCL24, MUC5a, Eotaxin, IL-38, and IL-8 were determined. Finally, lung histopathological features were evaluated. Treatment with probiotics could control AHR, eosinophil infiltration to the BALF and reduce the levels of immunoglobulins, IL-17, GTP and also decrease mucus secretion, goblet cell hyperplasia, peribronchial and perivascular inflammation and also, EPO activity. It could reduce gene expression of TLR4 and CCL11. On the other hand, IL-38 gene expression was increased by both probiotic and prebiotic treatment. Treatment with probiotics and prebiotics could control levels of IL-4, 5, 13, 25, 33, leukotrienes, the gene expression of AKT, NLR3, NF-κB, MyD88, MUC5a. The prebiotic treatment could control peribronchial inflammation and PI3K gene expression. Both of the treatments had no significant effect on the GOT, TSLP and IL-8, eotaxin and CCL24 gene expression. Probiotics and prebiotics could induce tolerance in allegro-inflammatory reactions and alter immune responses in allergic conditions. Probiotics could also modulate cellular and humoral immune responses and prevent allergic disorders.

摘要

哮喘是一种常见的呼吸道疾病,免疫系统失调与哮喘发病机制直接相关。益生菌和益生元具有免疫调节作用,可以调节免疫反应,可能减轻过敏反应。因此,本研究探讨了益生菌和益生元在调节急性气道炎症和 TLR4/NF-kB 通路中的作用。制作 BALB/c 小鼠过敏性哮喘模型,并给予益生菌(LA-5、GG 和 BB-12)和益生元(FOS 和 GOS)治疗。然后测量 AHR、BALF 细胞计数、EPO 活性、IL-4、5、13、17、25、33 以及 IFN-γ、总和 OVA 特异性 IgE、IgG1、Cys-LT、LTB4、LTC4 和 TSLP 水平。还进行了 GTP/GOT 测定,并测定了 Akt、NLR3、NF-kB、PI3K、MyD88、TLR4、CCL11、CCL24、MUC5a、Eotaxin、IL-38 和 IL-8 的基因表达。最后,评估了肺组织病理学特征。益生菌治疗可控制 AHR、嗜酸性粒细胞浸润 BALF 并降低免疫球蛋白、IL-17、GTP 水平,减少粘液分泌、杯状细胞增生、支气管周围和血管周围炎症以及 EPO 活性。它可以降低 TLR4 和 CCL11 的基因表达。另一方面,益生菌和益生元治疗均可增加 IL-38 基因表达。益生菌和益生元治疗可控制 IL-4、5、13、25、33、白三烯的水平、AKT、NLR3、NF-κB、MyD88、MUC5a 的基因表达。益生元治疗可控制支气管周围炎症和 PI3K 基因表达。两种治疗方法对 GOT、TSLP 和 IL-8、Eotaxin 和 CCL24 基因表达均无显著影响。益生菌和益生元可诱导过敏性炎症反应中的耐受,并改变过敏性疾病中的免疫反应。益生菌还可以调节细胞和体液免疫反应,预防过敏疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84b4/8925173/48144ca8cca5/12967_2022_3337_Fig1_HTML.jpg

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