罗滢;王苏华;林雪波;

• 1:宁波大学附属人民医院

摘要(Abstract)：

B3型柯萨奇病毒（Coxsackie virus B3,CVB3）与1型糖尿病发病、胰岛功能破坏有关，但CVB3对胰岛β细胞凋亡的影响及机制尚不清楚。本研究的目的是观察CVB3上调NF-κB p-p65引起胰岛β细胞凋亡的作用及机制，进而初步探究CVB3感染引起胰岛β细胞损伤的分子机制。本研究培养了人胰岛β细胞株，分为对照组、CVB3组、阴性对照（NC）质粒组、NF-κB p65质粒组、si-NC组、si-NC+CVB3组、si-NF-κB p65+CVB3组，检测细胞活力A490水平、细胞凋亡率及细胞中cleaved caspase-3、NF-κB p-p65、IκB α的表达水平。结果显示与对照组比较，CVB3组的A490水平及细胞中IκB α的表达水平降低，细胞凋亡率及细胞中cleaved caspase-3、NF-κB p-p65的表达水平增加（P<0.05）；与NC质粒组比较，NF-κB p65质粒组的A490水平降低，细胞凋亡率及细胞中cleaved caspase-3、NF-κB p-p65的表达水平增加（P<0.05）；与si-NC+CVB3组比较，si-NF-κB p65+CVB3组的A490水平增加，细胞凋亡率及细胞中cleaved caspase-3、NF-κB p-p65的表达水平降低（P<0.05）。以上结果表明CVB3感染能够促进胰岛β细胞凋亡，这一促凋亡作用与上调NF-κB有关。本文的创新在于探讨了NF-κB参与CVB3感染引起胰岛β细胞凋亡的过程，表明CVB3感染通过上调NF-κB引起胰岛β细胞凋亡，进而参与1型糖尿病的发病。

关键词(KeyWords)： 1型糖尿病;B3型柯萨奇病毒(CVB3);胰岛β细胞;凋亡;NF-κB

Abstract:

Keywords:

基金项目(Foundation):

作者(Authors): 罗滢;王苏华;林雪波;

DOI: 10.13242/j.cnki.bingduxuebao.004231

参考文献(References)：

• [1]Mine K,Yoshikai Y,Takahashi H,Mori H,Anzai K,Nagafuchi S. Genetic susceptibility of the host in virusinduced diabetes[J]. Microorganisms, 2020, 8(8):1133.
• [2]Chen HH, Lin IC, Chen HJ, Yeh SY, Kao CH.Association of herpes zoster and type 1 diabetes mellitus[J/OL]. PLoS One,2016,11(5):e0155175.
• [3]Allen DW, Kim KW, Rawlinson WD, Craig ME.Maternal virus infections in pregnancy and type 1diabetes in their offspring:Systematic review and metaanalysis of observational studies[J/OL]. Rev Med Virol,2018,28(3):e1974.
• [4]Bode MF,Schmedes CM,Egnatz GJ,Bharathi V,Hisada YM,Martinez D,KawanoT,Weithauser A,Rosenfeldt L,Rauch U,Palumbo JS,Antoniak S,Mackman N. Cell type-specific roles of PAR1 in Coxsackievirus B3 infection[J]. Sci Rep,2021,11(1):14264.
• [5]Cao H,Yang B,Zhao Y,Deng X,Shen X. The proapoptosis and pro-inflammation role of LncRNA HIF1AAS1 in Coxsackievirus B3-induced myocarditis via targeting miR-138[J]. Cardiovasc Diagn Ther,2020,10(5):1245-1255.
• [6]李莹莹，冯迎军.心肌康对病毒性心肌炎大鼠心肌Toll样受体4-核因子κB信号通路和细胞凋亡的影响[J].中华生物医学工程杂志，2019,25(1):7-12.
• [7]沈雅婧，李兰娟. B3型柯萨奇病毒感染对胰岛细胞糖尿病相关LncRNA表达的影响[J].中国临床药理学与治疗学，2019,24(10):1101-1106.
• [8]Geravandi S, Liu H, Maedler K. Enteroviruses and T1D:is it the virus,the genes or both which cause t1d[J]. Microorganisms,2020,8(7):1017.
• [9]Wernersson A,Sarmiento L,Cowan E,Fex M,Cilio CM. Human enteroviral infection impairs autophagy in clonal INS(832/13)cells and human pancreatic islet cells[J]. Diabetologia,2020,63(11):2372-2384.
• [10]谭琼，张鸿，杨菊，陈华明，赵明东，刘娟，丁小燕.柯萨奇B组病毒感染对1型糖尿病患儿胰岛功能的影响[J].临床误诊误治，2020,33(2):81-84.
• [11]Alhazmi A,Sane F,Lazrek M,Nekoua MP,BadiaBoungou F,Engelmann I,Alidjinou EK,Hober D.Enteroviruses and type 1 diabetes mellitus:an overlooked relationship in some regions[J].Microorganisms,2020,8(10):1458.
• [12]Wu R,Wu T,Li P,Wang Q,Shi Y,Zhan Y,Zhang S,Xia T,Wang Z,Lv H. The protection effects of survivin in the cell model of CVB3-induced viral myocarditis[J]. Heart Vessels,2020,35(8):1171-1179.
• [13]Wang X,Li M,Yu Y,Liu G,Yu Y,Zou Y,Ge J,Chen R. FTY720 alleviates coxsackievirus B3-induced myocarditis and inhibits viral replication through regulating sphingosine 1-phosphate receptors and AKT/caspase-3 pathways[J]. J Cell Physiol,2019,234(10):18029-18040.
• [14]Xie MY,Hou LJ,Sun JJ,Zeng B,Xi QY,Luo JY,Chen T,Zhang YL. Porcine milk exosome MiRNAs Attenuate LPS-Induced apoptosis through inhibiting TLR4/NF-kappaB and p53 pathways in intestinal epithelial cells[J]. J Agric Food Chem,2019,67(34):9477-9491.
• [15]Brennan K,Lyons C,Fernandes P,Doyle S,Houston A,Brint E. Engagement of Fas differentially regulates the production of LPS-induced proinflammatory cytokines and type I interferons[J]. FEBS J,2019,286(3):523-535.
• [16]Zhou D,Zhu Y,Ouyang MZ,Zhang M,Tang K,Niu CC,Li L. Knockout of Toll-like receptor 4 improves survival and cardiac function in a murine model of severe sepsis[J]. Mol Med Rep,2018,17(4):5368-5375.
• [17]Bako HY,Ibrahim MA,Isah MS,Ibrahim S. Inhibition of JAK-STAT and NF-kappaB signalling systems could be a novel therapeutic target against insulin resistance and type 2 diabetes[J]. Life Sci,2019,15(239):117045.
• [18]Liu Q,Zhang L,Zhang W,Hao Q,Qiu W,Wen Y,Wang H,Li X. Inhibition of NF-kappaB reduces renal inflammation and expression of pepck in type 2 diabetic mice[J]. Inflammation,2018,41(6):2018-2029.
• [19]简磊，胡斌，高明杰.过表达SIRT1抑制脂多糖诱导的胰岛β细胞炎症因子表达及NF-κB信号通路激活[J].免疫学杂志，2019,35(8):659-664.