[1]王丽萍,王恩光,张 俣.NOD 样受体热蛋白结构域相关蛋白3介导的细胞焦亡对哮喘大鼠炎症水平的调控作用[J].陕西医学杂志,2024,(4):449-454.[doi:DOI:10.3969/j.issn.1000-7377.2024.04.004]
　WANG Liping,WANG Enguang,ZHANG Yu.Regulation of pyroptosis mediated by NOD-like receptor pyrin domain-related protein 3 on inflammatory in asthmatic rats[J].,2024,(4):449-454.[doi:DOI:10.3969/j.issn.1000-7377.2024.04.004]
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NOD 样受体热蛋白结构域相关蛋白3介导的细胞焦亡对哮喘大鼠炎症水平的调控作用
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2024年4期
页码:
449-454
栏目:
基础研究
出版日期:
2024-04-05

文章信息/Info

Title:
Regulation of pyroptosis mediated by NOD-like receptor pyrin domain-related protein 3 on inflammatory in asthmatic rats
作者:
王丽萍; 王恩光; 张 俣
(新疆医科大学第五附属医院,新疆 乌鲁木齐 830011)
Author(s):
WANG Liping; WANG Enguang; ZHANG Yu
(The Fifth Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,China)
关键词:
哮喘;  NOD 样受体热蛋白结构域相关蛋白3;  细胞焦亡;  炎症;  凋亡
Keywords:
Asthma;  NOD-like receptor pyrin domain-related protein 3;  Pyroptosis;  Inflammation;  Apoptosis
分类号:
R -332
DOI:
DOI:10.3969/j.issn.1000-7377.2024.04.004
文献标志码:
A
摘要:
目的:探讨NOD 样受体热蛋白结构域相关蛋白3(NLRP3)在哮喘中炎症水平的调控作用机制。方法:从GSE40732和GSE69683数据集中分析哮喘组和对照组之间的差异表达基因(DEGs),并鉴定程序性细胞死亡在哮喘中的水平。在NLRP3敲降大鼠中建立哮喘大鼠模型,通过HE染色和Tunel染色分析肺组织的病理变化和凋亡水平,通过免疫组化检测肺组织中NLRP3的表达,通过实时荧光定量聚合酶链反应(RT-qPCR)和Western blot检测NLRP3介导细胞焦亡相关mRNA和蛋白表达的改变。结果:哮喘组和对照组之间鉴定了926个差异表达基因(DEGs),细胞焦亡在哮喘中的水平显著高于对照组。哮喘模型中的炎症、凋亡和NLRP3水平明显高于对照组,而在NLRP3敲降后,哮喘大鼠中的炎症和凋亡水平降低。与对照组比较,NLRP3、Gasdermin D蛋白(GSDMD)、胱天蛋白酶-1(Caspase-1)和Caspase-8在哮喘大鼠模型中的表达升高,高迁移率族蛋白1(HMGB1)的表达降低(均P<0.05),这些异常表达在NLRP3敲降后得到了显著的改善(P<0.05)。结论:NLRP3通过细胞焦亡信号可能在哮喘中发挥促炎促凋亡作用,阻断该通路可能是改善哮喘炎症的潜在治疗策略。
Abstract:
Objective: To explore the regulatory mechanism of NOD-like receptor pyrin domain-related protein 3(NLRP3)in asthma inflammation.Methods:Differential expression genes(DEGs)between asthma and control groups were analyzed from the GSE40732 and GSE69683 datasets,and the levels of programmed cell death were identified.An asthma rat model was established in NLRP3 knockdown rats,and pathological changes and apoptosis levels in lung tissue were analyzed using HE staining and TUNEL staining.Immunohistochemistry was employed to detect NLRP3 expression in lung tissue,and changes in NLRP3-mediated pyroptosis-related mRNA and protein expression were measured by RT-qPCR and Western blot.Results: A total of 926 DEGs were identified between asthma and control groups,and the level of pyroptosis was significantly higher in asthma(P<0.05).In the asthma model,inflammation,apoptosis,and NLRP3 levels were significantly higher compared to the control group(all P<0.05).However,after NLRP3 knockdown,inflammation and apoptosis levels were reduced in asthma rats(all P<0.05).Compared to the control group,the expressions of NLRP3,GSDMD,Caspase-1,and Caspase-8 were upregulated,while HMGB1 expression was downregulated in the asthma rat model(all P<0.05).These abnormal expressions were significantly improved after NLRP3 knockdown(all P<0.05).Conclusion: NLRP3 may exert a pro-inflammatory and pro-apoptotic role in asthma through the pyroptosis signaling pathway,and blocking this pathway can be a potential therapeutic strategy to improve asthma inflammation.

参考文献/References:

[1] HABIB N,PASHA M A,TANG D D.Current understanding of asthma pathogenesis and biomarkers[J].Cells,2022,11(17):2764.
[2] BRUSSELLE G G,KOPPELMAN G H.Biologic therapies for severe asthma[J].N Engl J Med,2022,386(2):157-171.
[3] GUIDA G,BAGNASCO D,CARRIERO V,et al.Critical evaluation of asthma biomarkers in clinical practice[J].Front Med(Lausanne),2022,9:969243.
[4] BEASLEY R,HARPER J,BIRD G,et al.Inhaled corticosteroid therapy in adult asthma.time for a new therapeutic dose terminology[J].Am J Respir Crit Care Med,2019,199(12):1471-1477.
[5] SETTIPANE R A,KREINDLER J L,CHUNG Y,et al.Evaluating direct costs and productivity losses of patients with asthma receiving GINA 4/5 therapy in the United States[J].Ann Allergy Asthma Immunol,2019,123(6):564-572.
[6] LIU L,ZHOU L,WANG L L,et al.Programmed cell death in asthma:Apoptosis,autophagy,pyroptosis,ferroptosis,and necroptosis[J].J Inflamm Res,2023,16:2727-2754.
[7] RADZIKOWSKA U,ELJASZEWICZ A,TAN G,et al.Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19[J].Nat Commun,2023,14(1):2329.
[8] XU P,LI F,TANG H.Pyroptosis and airway homeostasis regulation[J].Physiol Res,2023,72(1):1-13.
[9] SUN J,LI Y.Pyroptosis and respiratory diseases:A review of current knowledge[J].Front Immunol,2022,13:920464.
[10] WANG J L,HUA S N,BAO H J,et al.Pyroptosis and inflammasomes in cancer and inflammation[J].Med Comm(2020),2023,4(5):e374.
[11] LIU Y,LEI H,ZHANG W,et al.Pyroptosis in renal inflammation and fibrosis:Current knowledge and clinical significance[J].Cell Death Dis,2023,14(7):472.
[12] 刘华亭,郑博文,陈晨,等.基于NLRP3/Caspase-1/IL-1β信号通路探讨复方蛇龙胶囊对膜性肾病大鼠的作用[J].陕西中医,2023,44(6):709-716.
[13] CHAI R,LI Y,SHUI L,et al.The role of pyroptosis in inflammatory diseases[J].Front Cell Dev Biol,2023,11:1173235.
[14] ORNING P,LIEN E.Multiple roles of caspase-8 in cell death,inflammation,and innate immunity[J].J Leukoc Biol,2021,109(1):121-141.
[15] SHANG J,ZHAO F,CAO Y,et al.HMGB1 mediates lipopolysaccharide-induced macrophage autophagy and pyroptosis[J].BMC Mol Cell Biol,2023,24(1):2.
[16] 黄珊,宁佐伟,王国正,等.脂多糖通过NOD样受体蛋白3炎症小体通路诱导大鼠急性肝损伤实验研究[J].陕西医学杂志,2021,50(3):264-267,271.
[17] LIU L,ZHOU L,WANG L,et al.MUC1 attenuates neutrophilic airway inflammation in asthma by reducing NLRP3 inflammasome-mediated pyroptosis through the inhibition of the TLR4/MyD88/NF-kappaB pathway[J].Respir Res,2023,24(1):255.
[18] PAN L,CHEN Y,JIANG Y,et al.Yanghe pingchuan granules alleviate airway inflammation in bronchial asthma and inhibit pyroptosis by blocking the TLR4/NF-kappaB/NRLP3 signaling pathway[J].Mediators Inflamm,2022,2022:6561048.
[19] LESZCZYNSKA K,JAKUBCZYK D,GORSKA S.The NLRP3 inflammasome as a new target in respiratory disorders treatment[J].Front Immunol,2022,13:1006654.
[20] ZHANG X,WANG Z,ZHENG Y,et al.Inhibitors of the NLRP3 inflammasome pathway as promising therapeutic candidates for inflammatory diseases(Review)[J].Int J Mol Med,2023,51(4):35.
[21] WEI Y,YANG L,PANDEYA A,et al.Pyroptosis-induced inflammation and tissue damage[J].J Mol Biol,2022,434(4):167301.
[22] FENG Y,LI M,YANGZHONG X,et al.Pyroptosis in inflammation-related respiratory disease[J].J Physiol Biochem,2022,78(4):721-737.
[23] THEOFANI E,SEMITEKOLOU M,MORIANOS I,et al.Targeting NLRP3 inflammasome activation in severe asthma[J].J Clin Med,2019,8(10):1615.
[24] MULLA J,KATTI R,SCOTT M J.The role of gasdermin-d-mediated pyroptosis in organ injury and its therapeutic implications[J].Organogenesis,2023,19(1):2177484.
[25] TSAI Y M,CHIANG K H,HUNG J Y,et al.Der f1 induces pyroptosis in human bronchial epithelia via the NLRP3 inflammasome[J].Int J Mol Med,2018,41(2):757-764.
[26] 樊秋月,姜永红,陈一柳.清肺通络方通过胱天蛋白酶-1/Gasdermin D蛋白细胞焦亡途径对支原体肺炎小鼠的干预机制[J].陕西中医,2023,44(4):416-420.

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备注/Memo

备注/Memo:
基金项目:新疆维吾尔自治区自然科学基金资助项目(2022D01C312)
更新日期/Last Update: 2024-04-07