吴茱萸碱通过调节HMGB1/TLR4/NF-κB信号通路减轻大鼠输血相关性急性肺损伤*

doi:10.3969/j.issn.1671-2587.2023.05.004

临床输血与检验 ›› 2023, Vol. 25 ›› Issue (5): 599-606.DOI: 10.3969/j.issn.1671-2587.2023.05.004

吴茱萸碱通过调节HMGB1/TLR4/NF-κB信号通路减轻大鼠输血相关性急性肺损伤^*

乔剑, 刁春红, 于洋, 张娜, 常梦远

联勤保障部队第九八三医院输血医学科,天津 300142

收稿日期:2023-07-24 出版日期:2023-10-20 发布日期:2023-11-20
作者简介:乔剑,主要从事输血及血液疾病方向的研究,（E-mail）qiaojian983pla@163.com。
基金资助:
*本课题受天津市卫生健康委员会科技项目（No.TJWJ2022QN019）资助

Evodiamine Alleviates Blood Transfusion Related Acute Lung Injury in Rats by Regulating HMGB1/TLR4/NF-κB Signaling Pathway

QIAO Jian, DIAO Chunhong, YU Yang, et al

Department of Blood Transfusion Medicine, Joint Support Force 983 Hospital, Tianjin 300142

Received:2023-07-24 Online:2023-10-20 Published:2023-11-20

摘要/Abstract

摘要： 目的探究吴茱萸碱通过调节高迁移率族蛋白Bl（HMGB1）/Toll样受体4（TLR4）/核转录因子-κB（NF-κB）信号通路减轻大鼠输血相关性急性肺损伤（TRALI）的机制。方法取72只SD大鼠随机分为对照组、模型组、吴茱萸碱低剂量组、吴茱萸碱高剂量组、空载组、吴茱萸碱高剂量+HMGB1过表达组,每组12只,除对照组外,其余各组大鼠通过腹腔注射脂多糖（LPS）联合输注人血浆的方法制备TRALI模型。分组处理后检测各组大鼠肺功能指标吸气阻力（Ri）、每分钟通气量（MV）、呼气峰流速（PEF）;检测各组大鼠肺湿干比,苏木素-伊红（HE）染色检测肺组织病理形态变化;免疫荧光染色检测各组大鼠肺组织内血小板与中性粒细胞聚集情况;检测各组大鼠肺泡灌洗液（BALF）细胞总数和中性粒细胞百分比;酶联免疫吸附测定（ELISA）法检测各组大鼠BALF及血清促炎因子肿瘤坏死因子-α（TNF-α）、白细胞介素1β（IL-1β）水平;免疫印迹检测各组大鼠肺组织HMGB1/TLR4/NF-κB信号通路相关蛋白表达。结果与模型组相比,吴茱萸碱低剂量组、吴茱萸碱高剂量组大鼠肺功能指标MV、PEF均升高（P<0.05）,Ri、肺湿干比、肺组织病理评分、肺组织内血小板-中性粒细胞合光密度、BALF中细胞总数、中性粒细胞百分比、BALF及血清促炎因子TNF-α、IL-1β水平、肺组织HMGB1、TLR4蛋白表达与p-NF-κB p65/NF-κB p65均降低（P<0.05）。HMGB1过表达可减弱吴茱萸碱对TRALI大鼠肺功能的改善作用。结论吴茱萸碱可能通过抑制HMGB1/TLR4/NF-κB信号激活而抑制TRALI大鼠体内炎症,进而减轻其急性肺损伤,修复其肺功能。

关键词: 吴茱萸碱, 高迁移率族蛋白Bl/Toll样受体4/核转录因子-κB信号通路, 输血相关性急性肺损伤, 炎症, 肺功能

Abstract: Objective To investigate the mechanism by which evodiamine alleviates blood transfusion related acute lung injury (TRALI) in rats by regulating high mobility group protein Bl (HMGB1)/ toll like receptor 4 (TLR4)/nuclear transcription factor-κB (NF-κB) signaling pathway. Methods A total of 72 SD rats were randomly divided into the model group, low-dose evodiamine group, high-dose evodiamine group, no load group, high-dose evodiamine+HMGB1 overexpression group, and control group with 12 rats in each. Except for the control group, the TRALI model was prepared by intraperitoneal injection of lipopolysaccharide (LPS) combined with infusion of human plasma. After that, we analyzed the lung function indexes such as inspiratory resistance (Ri), minute ventilation (MV) and peak expiratory flow (PEF). Then, in each group we examined the lung wet-dry ratio of rats and the pathological changes of lung tissue by hematoxylin-eosin (HE) staining; the platelet and neutrophil aggregation in lung tissue by immunofluorescence staining; the total number of cells and the percentage of neutrophils in bronchoalveolar lavage fluid (BALF); the levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in BALF and serum by enzyme-linked immunosorbent assay (ELISA); as well as the expression of HMGB1/TLR4/NF-κB signaling pathway-related proteins in lung tissue by western blotting. Results Compared with the model group, the pulmonary function indexes MV and PEF in low-dose evodiamine group and high-dose evodiamine group were increased (P<0.05), while Ri, lung wet-dry ratio, lung histopathological score, platelet-neutrophil optical density in lung tissue, total number of cells in BALF, percentage of neutrophils, levels of pro-inflammatory factors TNF-α and IL-1β in BALF and serum, HMGB1 and TLR4 protein expression in lung tissue and p-NF-κB p65/NF-κB p65 were all decreased (P<0.05). Overexpression of HMGB1 attenuated the improvement of lung function by evodiamine in TRALI rats. Conclusion Evodiamine may inhibit the inflammation in TRALI rats by inhibiting the activation of HMGB1/TLR4/NF-κB signaling, thereby reducing its acute lung injury, and repairing its lung function.

Key words: Evodiamine, High mobility group protein Bl/toll like receptor 4/nuclear transcription factor-κB signaling pathway, Blood transfusion related acute lung injury, Inflammation, Lung function

中图分类号:

R457.1⁺3

乔剑, 刁春红, 于洋, 张娜, 常梦远. 吴茱萸碱通过调节HMGB1/TLR4/NF-κB信号通路减轻大鼠输血相关性急性肺损伤^*[J]. 临床输血与检验, 2023, 25(5): 599-606.

QIAO Jian, DIAO Chunhong, YU Yang, et al. Evodiamine Alleviates Blood Transfusion Related Acute Lung Injury in Rats by Regulating HMGB1/TLR4/NF-κB Signaling Pathway[J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2023, 25(5): 599-606.

参考文献

[1] KIM J,NA S.Transfusion-related acute lung injury;clinical perspectives[J].Korean J Anesthesiol,2015,68(2):101-105.
[2] 江颖,庄远,孙桂香,等.输血相关急性肺损伤的研究进展[J].解放军医学院学报,2020,41(8):826-829.
[3] ZEEUW VAN DER LAAN E A N,VAN DER VELDEN S,PORCELIJN L,et al.Update on the pathophysiology of transfusion-related acute lung injury[J].Curr Opin Hematol,2020,27(6):386-391.
[4] MENG L,LI L Y,LU S,et al.The protective effect of dexmedetomidine on LPS-induced acute lung injury through the HMGB1-mediated TLR4/NF-κB and PI3K/Akt/mTOR pathways[J].Mol Immunol,2018,94:7-17.
[5] ZHANG C H,WANG H,WANG H R,et al.A microsatellit e DNA-derived oligodeoxynucleotide attenuates lipopolysaccharide-induced acute lung injury in mice by inhibiting the HMGB1-TLR4-NF-κB signaling pathway[J].Front Microbiol,2022,13:964112.
[6] FAUST H,LAM L M,HOTZ M J,et al.RAGE interacts with the necroptotic protein RIPK3 and mediates transfusion-induced danger signal release[J].Vox Sang,2020,115(8):729-734.
[7] LE A P,WU Y Z,LIU W,et al.miR-144-induced KLF2 inhibition and NF-kappaB/CXCR1 activation promote neutrophil extracellular trap-induced transfusion-related acute lung injury[J].J Cellular Molecular Medi,2021,25(14):6511-6523.
[8] 梁靖蓉,麦凤怡,李陈广,等.吴茱萸碱的药理学研究进展[J].中国药理学通报,2022,38(10):1457-1461.
[9] 张莹,范霞,杨雪,等.吴茱萸碱对脓毒症小鼠急性肺损伤的保护作用[J].第三军医大学学报,2016,38(21):2309-2314.
[10] FAN X,ZHU J Y,SUN Y,et al.Evodiamine inhibits zymosan-induced inflammation in vitro and in vivo:inactivation of NF-κB by inhibiting IκBα phosphorylation[J].Inflammation,2017,40(3):1012-1027.
[11] WANG Q,CUI Y B,WU X F,et al.Evodiamine protects against airway remodelling and inflammation in asthmatic rats by modulating the HMGB1/NF-κB/TLR-4 signalling pathway[J].Pharm Biol,2021,59(1):190-197.
[12] 李丽玮,花紫菱,张惠箴,等.输血相关急性肺损伤大鼠模型建立及肺组织病理研究[J].中国输血杂志,2012,25(11):1121-1124.
[13] 章斌,姚永秀,彭裕红,等.吴茱萸碱对脂多糖诱导小鼠急性肺损伤的保护作用[J].中药药理与临床,2014,30(6):35-38.
[14] BUKOWCZAN J,WARZECHA Z,CERANOWICZ P,et al.Pretreatment with obestatin reduces the severity of ischemia/reperfusion-induced acute pancreatitis in rats[J].Eur J Pharmacol,2015,760:113-121.
[15] 卓孝福. 输血相关急性肺损伤的临床特征、诊断、治疗和预后[J].中国输血杂志,2014,27(12):1367-1370.
[16] SEMPLE J W,REBETZ J,KAPUR R.Transfusion-associated circulatory overload and transfusion-related acute lung injury[J].Blood,2019,133(17):1840-1853.
[17] 张志仙,蒋美玲,王欣慧,等.吴茱萸碱的药理学研究进展[J].现代生物医学进展,2014,14(21):4189-4191.
[18] ZHANG Y F,ZHANG Y Q,ZHAO Y,et al.Protection against ulcerative colitis and colorectal cancer by evodiamine via anti-inflammatory effects[J].Mol Med Rep,2022,25(5):188.
[19] 李有连,张秉丽,霍成英,等.吴茱萸碱对酒精性胃溃疡大鼠胃黏膜上皮细胞的保护作用[J].中南医学科学杂志,2022,50(2):184-189.
[20] 董悦,李竣,佟海英,等.基于网络药理学及分子对接探讨香连片对新型冠状病毒肺炎(COVID-19)的机制研究[J].中国医院药学杂志,2021,41(7):667-674.
[21] HE J,LIU M W,WANG Z Y,et al.Protective effects of the notoginsenoside R1 on acute lung injury by regulating the miR-128-2-5p/Tollip signaling pathway in rats with severe acute pancreatitis[J].Innate Immun,2022,28(1):19-36.
[22] JI C L,DAI S,LIU H,et al.Polyphenols from Securidaca inappendiculata alleviated acute lung injury in rats by inhibiting oxidative stress sensitive pathways[J].Chin Herb Med,2021,13(3):381-388.
[23] MORSING SOFIA K H,VAN DER LAAN EVELINE Z,VAN STALBORCH ANNEMARIEKE D,et al.A pulmonary endothelial amplification loop aggravates ex-vivo transfusion-related acute lung injury via increased toll-like receptor 4 and intra-cellular adhesion molecule-1 expression[J].Transfusion,2022,62(10):1961-1966.

吴茱萸碱通过调节HMGB1/TLR4/NF-κB信号通路减轻大鼠输血相关性急性肺损伤^*

Evodiamine Alleviates Blood Transfusion Related Acute Lung Injury in Rats by Regulating HMGB1/TLR4/NF-κB Signaling Pathway

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