氨甲环酸不同时间给药对血管内皮细胞多糖-蛋白质复合物降解的影响

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摘要目的：研究氨甲环酸（TXA）对体外人脐静脉内皮细胞（HUVECs）中多糖-蛋白质复合物降解的调节作用。方法：体外培养HUVECs，加入100 μmol/L的H2O2作用12 h，在H2O2作用开始后30 min和60 min以及H2O2作用结束前1 h和2 h这4个时间点加入150 μmol/L TXA；Hoechst 33258染色法观察HUVECs形态；Western blot法检测细胞内caspase-3、细胞间黏附分子（ICAM）和基质金属蛋白酶-9（MMP-9）的表达；ELISA检测细胞上清液多配体聚糖、透明质酸（HLA）和肿瘤坏死因子-α（TNF-α）含量；tran-swell小室实验检测体外血管内皮细胞侵袭行为。结果：HUVECs经H2O2作用后，可显著诱导细胞凋亡，上调caspase-3、ICAM、HLA和TNF-α的表达，同时促进体外内皮细胞侵袭行为（P＜0.05）；TXA在H2O2作用60 min内给药可抑制H2O2对HUVECs的凋亡诱导作用，同时下调caspase-3、ICAM、HLA和TNF-α的表达，并抑制内皮细胞侵袭行为（均P＜0.05）；TXA在经H2O2作用60 min后给药无上述保护作用（P＞0.05）。结论：早期TXA给药对H2O2诱导HUVECs中多糖-蛋白质复合物的降解有明显抑制作用。

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	胡磊

关键词 ：人脐静脉内皮细胞, 氨甲环酸, 多糖-蛋白质复合物

Abstract：Objective: To investigate the effect of tranexamic acid (TXA) on glycocalyx damage in human umbilical vein endothelial cells (HUVECs) following H2O2 injury. Methods: In vitro HUVECs were exposed to H2O2 to stimulate post-shock reperfusion. TXA was added during H2O2 incubation (30 minutes and 60 minutes) and at 1 hour and 2 hours before the termination of H2O2 exposure. The cellular morphology was observed using a ﬂuorescence microscope after Hoechst 33258 staining. Endothelial cell injury was indexed by caspase-3 as well as ICAM expression and TNF-α release. Glycocalyx degradation was indexed by syndecan and HLA release. Activation of endothelial sheddases was indexed by MMP-9 content in HUVECs. Transwell assay was performed to explore the invasive property of HUVECs. Results: Exposure of HUVECs to H2O2 results in glycocalyx disruption demonstrated by promoted apoptosis and increased levels of caspase-3, syndecan, HLA, TNF-α, ICAM and MMP-9. TXA administration within 60 minutes of H2O2 treatment results in preservation of the glycocalyx. TXA administration after 60 minutes is no glycocalyx protective effect on HUVECs. Conclusion: TXA is exerted as an endothelial protector via inhibition of glycocalyx degradation. This effect is not apparent when TXA was administered after 60 minutes of H2O2 exposure.

Key words： human umbilical vein endothelial cells tranexamic acid glycocalyx

收稿日期: 2018-01-09

基金资助:浙江省重大科技专项重大社会发展项目（2016C03021）。

作者简介: 胡磊（1984-），男，浙江金华人，主治医师。

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https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2018/V48/I10/712

[1] JIANG X Z, GONG H, LUO K H, et al. Large-scale molecular dynamics simulation of coupled dynamics of flow and glycocalyx: towards understanding atomic events on an endothelial cell surface[J]. J R Soc Interface, 2017, 14(137): 20170780.
[2] GONZALEZ RODRIGUEZ E, OSTROWSKI S R, CARDENAS J C, et al. Syndecan-1: A quantitative marker for the endotheliopathy of trauma[J]. J Am Coll Surg, 2017, 225(3): 419-427.
[3] FLAHERTY K, BATH P M, DINEEN R, et al. Statistical analysis plan for the ‘Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage’ (TICH-2) trial[J]. Trials, 2017, 18(1): 607.
[4] BOETTNER F, RUECKL K. Benefits of tranexamic acid not debatable but leave tourniquet use to surgeon’s discretion: commentary on an article by ZeYu Huang, MD, PhD, et al.: “Intravenous and topical tranexamic acid alone are superior to tourniquet use for primary total knee arthroplasty. A prospective, randomized controlled trial”[J]. J Bone Joint Surg Am, 2017, 99(24): e135.
[5] LI T, LIU X, ZHAO Z, et al. Sulodexide recovers endothelial function through reconstructing glycocalyx in the balloon-injury rat carotid artery model[J]. Oncotarget, 2017, 8(53): 91350-91361.
[6] TARGOSZ-KORECKA M, JAGLARZ M, MALEK-ZIETEK K E, et al. AFM-based detection of glycocalyx degradation and endothelial stiffening in the db/db mouse model of diabetes[J]. Sci Rep, 2017, 7(1): 15951.
[7] YAN J, WANG J, HUANG H, et al. Fibroblast growth factor 21 delayed endothelial replicative senescence and protected cells from H2O2-induced premature senescence through SIRT1[J]. Am J Transl Res, 2017, 9(10): 4492-4501.
[8] LIOU C J, HUANG W C. Casticin inhibits interleukin-1β-induced ICAM-1 and MUC5AC expression by blocking NF-κB, PI3K-Akt, and MAPK signaling in human lung epithelial cells[J]. Oncotarget, 2017, 8(60): 101175-101188.
[9] GALORE-HASKE G, BARUCH E N, BERG A L, et al. Histopathological expression analysis of intercellular adhesion molecule 1 (ICAM-1) along development and progression of human melanoma[J]. Oncotarget, 2017, 8(59): 99580-99586.
[10] KURNIK N M, PFLIBSEN L R, DO A, et al. Craniosynostosis surgery and the impact of tranexamic acid dosing[J]. J Craniofac Surg, 2018, 29(1): 96-98.
[11] BUTWICK A J, DENEUX-THARAUX C, SENTILHES L. Tranexamic acid for the management of obstetric hemor-rhage[J]. Obstet Gynecol, 2017, 130(6): 1386.
[12] DUEBEL L N, MARTIN J V, LIBERATI D M. Early tranexamic acid administration ameliorates the endotheliopathy of trauma and shock in an in vitro model[J]. J Trauma Acute Care Surg, 2017, 82(6): 1080-1086.
[13] GIEGER T L, NETTIFEE-OSBORNE J, HALLMAN B,
et al. The impact of carboplatin and toceranib phosphate on serum vascular endothelial growth factor (VEGF) and metalloproteinase-9 (MMP-9) levels and survival in canine os-teosarcoma[J]. Can J Vet Res, 2017, 81(3): 199-205.
[14] COOPER S, MCDONALD K, BURKAT D, et al. Stenosis Hemodynamics disrupt the endothelial cell glycocalyx by MMP activity creating a proinflammatory environment[J]. Ann Biomed Eng, 2017, 45(9): 2234-2243.
[15] ALONI P D, NAYAK A R, CHAURASIA S R, et al. Effect of Fagonia arabica on thrombin induced release of t-PA and complex of PAI-1 tPA in cultured HUVE cells[J]. J Tradit Complement Med, 2015, 6(3): 219-223.
[16] ALTAF M, STOECKLI-EVANS H. A copper(II) paddle-wheel structure of tranexamic acid: di-chloro-tetra-kis-[μ-4-(ammonio-meth-yl)cyclo-hexane-1-carboxyl-ato-O,O’]dicopper(II) dichloride hexa-hydrate[J]. Acta Crystallogr E Crystallogr Commun, 2017, 73(Pt 10): 1421-1425.
[17] DIEBEL L N, MARTIN J V, LIBERATI D M. Early tranexamic acid administration ameliorates the endotheliopathy of trauma and shock in an in vitro model[J]. J Trauma Acute Care Surg, 2017, 82(6): 1080-1086.