保護與重建內皮糖萼：膿毒癥治療新靶點_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

劉騏源 ¹ ,  李愛民 ²

1. ;
2. ;

Corresponding?author：

李愛民, Email: dcliaim@163.com

Keywords：

DOI：

10.7507/1671-6205.202410111

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Citation： 劉騏源, 李愛民. 保護與重建內皮糖萼：膿毒癥治療新靶點. Chinese Journal of Respiratory and Critical Care Medicine, 2025, 24(9): 675-679. doi: 10.7507/1671-6205.202410111 Copy

1.	Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA, 2016, 315(8): 801-810.
2.	Arina P, Singer M. Pathophysiology of sepsis. Curr Opin Anaesthesiol, 2021, 34(2): 77-84.
3.	Fernández-Sarmiento J, Salazar-Peláez LM, Carcillo JA. The endothelial glycocalyx: a fundamental determinant of vascular permeability in sepsis. Pediatr Crit Care Med, 2020, 21(5): E291-E300.
4.	Marik P, Bellomo R. A rational approach to fluid therapy in sepsis. Br J Anaesth, 2016, 116(3): 339-349.
5.	Weinbaum S, Tarbell JM, Damiano ER. The structure and function of the endothelial glycocalyx layer. Annu Rev Biomed Eng, 2007, 9: 121-167.
6.	Broekhuizen LN, Mooij HL, Kastelein JJ, et al. Endothelial glycocalyx as potential diagnostic and therapeutic target in cardiovascular disease. Curr Opin Lipidol, 2009, 20(1): 57-62.
7.	Jedlicka J, Becker BF, Chappell D. Endothelial glycocalyx. Crit Care Clin, 2020, 36(2): 217-232.
8.	Vink H, Duling BR. Identification of distinct luminal domains for macromolecules, erythrocytes, and leukocytes within mammalian capillaries. Circ Res, 1996, 79(3): 581-589.
9.	Foote CA, Soares RN, Ramirez-Perez FI, et al. Endothelial glycocalyx. Compr Physiol, 2022, 12(4): 3781-811.
10.	Vittum Z, Cocchiaro S, Mensah SA. Basal endothelial glycocalyx's response to shear stress: a review of structure, function, and clinical implications. Front Cell Dev Biol, 2024, 12: 1371769.
11.	Kumar AV, Katakam SK, Urbanowitz AK, et al. Heparan sulphate as a regulator of leukocyte recruitment in inflammation. Curr Protein Pept Sci, 2015, 16(1): 77-86.
12.	Wang T, Zhao J, Zhang J, et al. Heparan sulfate inhibits inflammation and improves wound healing by downregulating the NLR family pyrin domain containing 3 (NLRP3) inflammasome in diabetic rats. J Diabetes, 2018, 10(7): 556-563.
13.	Liu HQ, Li J, Xuan CL, et al. A review on the physiological and pathophysiological role of endothelial glycocalyx. J Biochem Mol Toxicol, 2020, 34(11): e22571.
14.	Cao JJ, Chen Y. The impact of vascular endothelial glycocalyx on the pathogenesis and treatment of disseminated intravascular coagulation. Blood Coagul Fibrinolysis, 2023, 34(8): 465-470.
15.	Ali MM, Mahmoud AM, Le Master E, et al. Role of matrix metalloproteinases and histone deacetylase in oxidative stress-induced degradation of the endothelial glycocalyx. Am J Physiol Heart Circ Physiol, 2019, 316(3): H647-h663.
16.	Cicchinelli S, Pignataro G, Gemma S, et al. PAMPs and DAMPs in sepsis: a review of their molecular features and potential clinical implications. Int J Mol Sci, 2024, 25(2): 962.
17.	Goligorsky MS, Sun D. Glycocalyx in Endotoxemia and Sepsis. Am J Pathol, 2020, 190(4): 791-798.
18.	Schmidt EP, Yang Y, Janssen WJ, et al. The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis. Nat Med, 2012, 18(8): 1217-1223.
19.	Yang X, Meegan JE, Jannaway M, et al. A disintegrin and metalloproteinase 15-mediated glycocalyx shedding contributes to vascular leakage during inflammation. Cardiovasc Res, 2018, 114(13): 1752-1763.
20.	Martin L, De Santis R, Koczera P, et al. The Synthetic antimicrobial peptide 19-2. 5 interacts with heparanase and heparan sulfate in murine and human sepsis. PLoS One, 2015, 10(11): e0143583.
21.	Saravi B, Goebel U, Hassenzahl LO, et al. Capillary leak and endothelial permeability in critically ill patients: a current overview. Intensive Care Med Exp, 2023, 11(1): 96.
22.	Larivière WB, Schmidt EP. The Pulmonary endothelial glycocalyx in ARDS: a critical role for heparan sulfate. Curr Top Membr, 2018, 82: 33-52.
23.	Drost CC, Rovas A, Kusche-Vihrog K, et al. Tie2 activation promotes protection and reconstitution of the endothelial glycocalyx in human sepsis. Thromb Haemost, 2019, 119(11): 1827-1838.
24.	Hakanpaa L, Sipila T, Leppanen VM, et al. Endothelial destabilization by angiopoietin-2 via integrin β1 activation. Nat Commun, 2015, 6: 5962.
25.	Brouns SLN, Provenzale I, Van Geffen JP, et al. Localized endothelial-based control of platelet aggregation and coagulation under flow: A proof-of-principle vessel-on-a-chip study. J Thromb Haemost, 2020, 18(4): 931-941.
26.	Becker BF, Jacob M, Leipert S, et al. Degradation of the endothelial glycocalyx in clinical settings: searching for the sheddases. Br J Clin Pharmacol, 2015, 80(3): 389-402.
27.	Piotti A, Novelli D, Meessen J, et al. Endothelial damage in septic shock patients as evidenced by circulating syndecan-1, sphingosine-1-phosphate and soluble VE-cadherin: a substudy of ALBIOS. Crit Care, 2021, 25(1): 113.
28.	周高生, 劉晶晶, 張宏民, 等. 多配體聚糖-1和可溶性血栓調節蛋白對膿毒癥患者病情嚴重程度及預后的預測價值. 中國急救醫學, 2022, 42(11): 921-928.
29.	Lekakis J, Abraham P, Balbarini A, et al. Methods for evaluating endothelial function: a position statement from the European Society of Cardiology Working Group on Peripheral Circulation. Eur J Cardiovasc Prev Rehabil, 2011, 18(6): 775-789.
30.	Rovas A, Seidel LM, Vink H, et al. Association of sublingual microcirculation parameters and endothelial glycocalyx dimensions in resuscitated sepsis. Crit Care, 2019, 23(1): 260.
31.	Cerny V, Astapenko D, Burkovskiy I, et al. Glycocalyx in vivo measurement. Clin Hemorheol Microcirc, 2017, 67(3-4): 499-503.
32.	Silversides JA, Perner A, Malbrain M. Liberal versus restrictive fluid therapy in critically ill patients. Intensive Care Med, 2019, 45(10): 1440-1442.
33.	Meyhoff TS, Hjortrup PB, M?ller MH, et al. Conservative vs liberal fluid therapy in septic shock (CLASSIC) trial-Protocol and statistical analysis plan. Acta Anaesthesiol Scand, 2019, 63(9): 1262-1271.
34.	Zampieri FG, Bagshaw SM, Semler MW. fluid therapy for critically ill adultswith sepsis: a review. JAMA, 2023, 329(22): 1967-1980.
35.	Kuhn M. Endothelial actions of atrial and B-type natriuretic peptides. Br J Pharmacol, 2012, 166(2): 522-531.
36.	Meyhoff TS, Hjortrup PB, Wetterslev J, et al. Restriction of intravenous fluid in ICU patients with septic shock. N Engl J Med, 2022, 386(26): 2459-2470.
37.	Ho L, Lau L, Churilov L, et al. Comparative evaluation of crystalloid resuscitation rate in a human model of compensated haemorrhagic shock. Shock, 2016, 46(2): 149-157.
38.	Iro MA, Sell T, Brown N, et al. Rapid intravenous rehydration of children with acute gastroenteritis and dehydration: a systematic review and meta-analysis. BMC Pediatr, 2018, 18(1): 44.
39.	Cheung-Flynn J, Alvis BD, Hocking KM, et al. Normal saline solutions cause endothelial dysfunction through loss of membrane integrity, ATP release, and inflammatory responses mediated by P2X7R/p38 MAPK/MK2 signaling pathways. PLoS One, 2019, 14(8): e0220893.
40.	Jacob M, Bruegger D, Rehm M, et al. Contrasting effects of colloid and crystalloid resuscitation fluids on cardiac vascular permeability. Anesthesiology, 2006, 104(6): 1223-1231.
41.	Diebel LN, Liberati DM, Carge M. Effect of albumin solutions on endothelial oxidant injury: a microfluidic study. Surgery, 2023, 173(3): 876-882.
42.	徐宇治, 孫立群. 1-磷酸鞘氨醇在膿毒癥診療中的應用前景. 中國呼吸與危重監護雜志, 2022, 21(5): 370-373.
43.	Curry FE, Adamson RH. Endothelial glycocalyx: permeability barrier and mechanosensor. Ann Biomed Eng, 2012, 40(4): 828-839.
44.	Tarbell JM, Simon SI, Curry FR. Mechanosensing at the vascular interface. Annu Rev Biomed Eng, 2014, 16: 505-532.
45.	Zeng Y, Adamson RH, Curry FRE, et al. Sphingosine-1-phosphate protects endothelial glycocalyx by inhibiting syndecan-1 shedding. Am J Physiol Heart Circ Physiol, 2014, 306(3): H363-H72.
46.	Jacob M, Bruegger D, Rehm M, et al. The endothelial glycocalyx affords compatibility of Starling's principle and high cardiac interstitial albumin levels. Cardiovasc Res, 2007, 73(3): 575-586.
47.	Kravitz MS, Kattouf N, Stewart IJ, et al. Plasma for prevention and treatment of glycocalyx degradation in trauma and sepsis. Critical Care, 2024, 28(1): 254.
48.	Reitsma S, Slaaf DW, Vink H, et al. The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch, 2007, 454(3): 345-359.
49.	Ali FF, Mohammed MM, Hussein Y, et al. Targeting PI3K/p-Akt/eNOS, Nrf2/HO-1, and NF-κB/p53 signaling pathways by angiotensin 1-7 protects against liver injury induced by ischemia-reperfusion in rats. Cell Biochem Funct, 2024, 42(1): e3938.
50.	Han S, Lee SJ, Kim KE, et al. Amelioration of sepsis by TIE2 activation-induced vascular protection. Sci Transl Med, 2016, 8(335): 335ra55.
51.	Luxen M, Van Meurs M, Molema G. Unlocking the untapped potential of endothelial kinase and phosphatase involvement in sepsis for drug treatment design. Front Immunol, 2022, 13: 867625.
52.	David S, Russell L, Castro P, et al. Research priorities for therapeutic plasma exchange in critically ill patients. Intensive Care Med Exp, 2023, 11(1): 26.
53.	Knaup H, Stahl K, Schmidt BMW, et al. Early therapeutic plasma exchange in septic shock: a prospective open-label nonrandomized pilot study focusing on safety, hemodynamics, vascular barrier function, and biologic markers. Crit Care, 2018, 22(1): 285.
54.	Iba T, Levy JH, Aihara K, et al. Newly developed recombinant antithrombin protects the endothelial glycocalyx in an endotoxin-induced rat model of sepsis. Int J Mol Sci, 2020, 22(1): 176.
55.	Suzuki K, Okada H, Takemura G, et al. Recombinant thrombomodulin protects against LPS-induced acute respiratory distress syndrome via preservation of pulmonary endothelial glycocalyx. Br J Pharmacol, 2020, 177(17): 4021-4033.
56.	Kikuchi K, Kazuma S, Yamakage M. Recombinant thrombomodulin and recombinant antithrombin attenuate pulmonary endothelial glycocalyx degradation and neutrophil extracellular trap formation in ventilator-induced lung injury in the context of endotoxemia. Respir Res, 2024, 25(1): 330.
57.	Machin DR, Sabouri M, Zheng XY, et al. Therapeutic strategies targeting the endothelial glycocalyx. Curr Opin Clin Nutr Metab Care, 2023, 26(6): 543-550.
58.	Masola V, Onisto M, Zaza G, et al. A new mechanism of action of sulodexide in diabetic nephropathy: inhibits heparanase-1 and prevents FGF-2-induced renal epithelial-mesenchymal transition. J Transl Med, 2012, 10: 213.
59.	Ying J, Zhang C, Wang Y, et al. Sulodexide improves vascular permeability via glycocalyx remodelling in endothelial cells during sepsis. Front Immunol, 2023, 14: 1172892.
60.	劉瓊, 王金榮, 崔朝勃. 氫化可的松、維生素C和維生素B1聯合治療膿毒癥研究進展. 中國呼吸與危重監護雜志, 2021, 20(5): 366-371.
61.	Pietrasanta C, Pugni L, Ronchi A, et al. Vascular endothelium in neonatal sepsis: basic mechanisms and translational opportunities. Front Pediatr, 2019, 7: 340.
62.	Chappell D, Jacob M, Hofmann-Kiefer K, et al. Hydrocortisone preserves the vascular barrier by protecting the endothelial glycocalyx. Anesthesiology, 2007, 107(5): 776-784.

1. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA, 2016, 315(8): 801-810.
2. Arina P, Singer M. Pathophysiology of sepsis. Curr Opin Anaesthesiol, 2021, 34(2): 77-84.
3. Fernández-Sarmiento J, Salazar-Peláez LM, Carcillo JA. The endothelial glycocalyx: a fundamental determinant of vascular permeability in sepsis. Pediatr Crit Care Med, 2020, 21(5): E291-E300.
4. Marik P, Bellomo R. A rational approach to fluid therapy in sepsis. Br J Anaesth, 2016, 116(3): 339-349.
5. Weinbaum S, Tarbell JM, Damiano ER. The structure and function of the endothelial glycocalyx layer. Annu Rev Biomed Eng, 2007, 9: 121-167.
6. Broekhuizen LN, Mooij HL, Kastelein JJ, et al. Endothelial glycocalyx as potential diagnostic and therapeutic target in cardiovascular disease. Curr Opin Lipidol, 2009, 20(1): 57-62.
7. Jedlicka J, Becker BF, Chappell D. Endothelial glycocalyx. Crit Care Clin, 2020, 36(2): 217-232.
8. Vink H, Duling BR. Identification of distinct luminal domains for macromolecules, erythrocytes, and leukocytes within mammalian capillaries. Circ Res, 1996, 79(3): 581-589.
9. Foote CA, Soares RN, Ramirez-Perez FI, et al. Endothelial glycocalyx. Compr Physiol, 2022, 12(4): 3781-811.
10. Vittum Z, Cocchiaro S, Mensah SA. Basal endothelial glycocalyx's response to shear stress: a review of structure, function, and clinical implications. Front Cell Dev Biol, 2024, 12: 1371769.
11. Kumar AV, Katakam SK, Urbanowitz AK, et al. Heparan sulphate as a regulator of leukocyte recruitment in inflammation. Curr Protein Pept Sci, 2015, 16(1): 77-86.
12. Wang T, Zhao J, Zhang J, et al. Heparan sulfate inhibits inflammation and improves wound healing by downregulating the NLR family pyrin domain containing 3 (NLRP3) inflammasome in diabetic rats. J Diabetes, 2018, 10(7): 556-563.
13. Liu HQ, Li J, Xuan CL, et al. A review on the physiological and pathophysiological role of endothelial glycocalyx. J Biochem Mol Toxicol, 2020, 34(11): e22571.
14. Cao JJ, Chen Y. The impact of vascular endothelial glycocalyx on the pathogenesis and treatment of disseminated intravascular coagulation. Blood Coagul Fibrinolysis, 2023, 34(8): 465-470.
15. Ali MM, Mahmoud AM, Le Master E, et al. Role of matrix metalloproteinases and histone deacetylase in oxidative stress-induced degradation of the endothelial glycocalyx. Am J Physiol Heart Circ Physiol, 2019, 316(3): H647-h663.
16. Cicchinelli S, Pignataro G, Gemma S, et al. PAMPs and DAMPs in sepsis: a review of their molecular features and potential clinical implications. Int J Mol Sci, 2024, 25(2): 962.
17. Goligorsky MS, Sun D. Glycocalyx in Endotoxemia and Sepsis. Am J Pathol, 2020, 190(4): 791-798.
18. Schmidt EP, Yang Y, Janssen WJ, et al. The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis. Nat Med, 2012, 18(8): 1217-1223.
19. Yang X, Meegan JE, Jannaway M, et al. A disintegrin and metalloproteinase 15-mediated glycocalyx shedding contributes to vascular leakage during inflammation. Cardiovasc Res, 2018, 114(13): 1752-1763.
20. Martin L, De Santis R, Koczera P, et al. The Synthetic antimicrobial peptide 19-2. 5 interacts with heparanase and heparan sulfate in murine and human sepsis. PLoS One, 2015, 10(11): e0143583.
21. Saravi B, Goebel U, Hassenzahl LO, et al. Capillary leak and endothelial permeability in critically ill patients: a current overview. Intensive Care Med Exp, 2023, 11(1): 96.
22. Larivière WB, Schmidt EP. The Pulmonary endothelial glycocalyx in ARDS: a critical role for heparan sulfate. Curr Top Membr, 2018, 82: 33-52.
23. Drost CC, Rovas A, Kusche-Vihrog K, et al. Tie2 activation promotes protection and reconstitution of the endothelial glycocalyx in human sepsis. Thromb Haemost, 2019, 119(11): 1827-1838.
24. Hakanpaa L, Sipila T, Leppanen VM, et al. Endothelial destabilization by angiopoietin-2 via integrin β1 activation. Nat Commun, 2015, 6: 5962.
25. Brouns SLN, Provenzale I, Van Geffen JP, et al. Localized endothelial-based control of platelet aggregation and coagulation under flow: A proof-of-principle vessel-on-a-chip study. J Thromb Haemost, 2020, 18(4): 931-941.
26. Becker BF, Jacob M, Leipert S, et al. Degradation of the endothelial glycocalyx in clinical settings: searching for the sheddases. Br J Clin Pharmacol, 2015, 80(3): 389-402.
27. Piotti A, Novelli D, Meessen J, et al. Endothelial damage in septic shock patients as evidenced by circulating syndecan-1, sphingosine-1-phosphate and soluble VE-cadherin: a substudy of ALBIOS. Crit Care, 2021, 25(1): 113.
28. 周高生, 劉晶晶, 張宏民, 等. 多配體聚糖-1和可溶性血栓調節蛋白對膿毒癥患者病情嚴重程度及預后的預測價值. 中國急救醫學, 2022, 42(11): 921-928.
29. Lekakis J, Abraham P, Balbarini A, et al. Methods for evaluating endothelial function: a position statement from the European Society of Cardiology Working Group on Peripheral Circulation. Eur J Cardiovasc Prev Rehabil, 2011, 18(6): 775-789.
30. Rovas A, Seidel LM, Vink H, et al. Association of sublingual microcirculation parameters and endothelial glycocalyx dimensions in resuscitated sepsis. Crit Care, 2019, 23(1): 260.
31. Cerny V, Astapenko D, Burkovskiy I, et al. Glycocalyx in vivo measurement. Clin Hemorheol Microcirc, 2017, 67(3-4): 499-503.
32. Silversides JA, Perner A, Malbrain M. Liberal versus restrictive fluid therapy in critically ill patients. Intensive Care Med, 2019, 45(10): 1440-1442.
33. Meyhoff TS, Hjortrup PB, M?ller MH, et al. Conservative vs liberal fluid therapy in septic shock (CLASSIC) trial-Protocol and statistical analysis plan. Acta Anaesthesiol Scand, 2019, 63(9): 1262-1271.
34. Zampieri FG, Bagshaw SM, Semler MW. fluid therapy for critically ill adultswith sepsis: a review. JAMA, 2023, 329(22): 1967-1980.
35. Kuhn M. Endothelial actions of atrial and B-type natriuretic peptides. Br J Pharmacol, 2012, 166(2): 522-531.
36. Meyhoff TS, Hjortrup PB, Wetterslev J, et al. Restriction of intravenous fluid in ICU patients with septic shock. N Engl J Med, 2022, 386(26): 2459-2470.
37. Ho L, Lau L, Churilov L, et al. Comparative evaluation of crystalloid resuscitation rate in a human model of compensated haemorrhagic shock. Shock, 2016, 46(2): 149-157.
38. Iro MA, Sell T, Brown N, et al. Rapid intravenous rehydration of children with acute gastroenteritis and dehydration: a systematic review and meta-analysis. BMC Pediatr, 2018, 18(1): 44.
39. Cheung-Flynn J, Alvis BD, Hocking KM, et al. Normal saline solutions cause endothelial dysfunction through loss of membrane integrity, ATP release, and inflammatory responses mediated by P2X7R/p38 MAPK/MK2 signaling pathways. PLoS One, 2019, 14(8): e0220893.
40. Jacob M, Bruegger D, Rehm M, et al. Contrasting effects of colloid and crystalloid resuscitation fluids on cardiac vascular permeability. Anesthesiology, 2006, 104(6): 1223-1231.
41. Diebel LN, Liberati DM, Carge M. Effect of albumin solutions on endothelial oxidant injury: a microfluidic study. Surgery, 2023, 173(3): 876-882.
42. 徐宇治, 孫立群. 1-磷酸鞘氨醇在膿毒癥診療中的應用前景. 中國呼吸與危重監護雜志, 2022, 21(5): 370-373.
43. Curry FE, Adamson RH. Endothelial glycocalyx: permeability barrier and mechanosensor. Ann Biomed Eng, 2012, 40(4): 828-839.
44. Tarbell JM, Simon SI, Curry FR. Mechanosensing at the vascular interface. Annu Rev Biomed Eng, 2014, 16: 505-532.
45. Zeng Y, Adamson RH, Curry FRE, et al. Sphingosine-1-phosphate protects endothelial glycocalyx by inhibiting syndecan-1 shedding. Am J Physiol Heart Circ Physiol, 2014, 306(3): H363-H72.
46. Jacob M, Bruegger D, Rehm M, et al. The endothelial glycocalyx affords compatibility of Starling's principle and high cardiac interstitial albumin levels. Cardiovasc Res, 2007, 73(3): 575-586.
47. Kravitz MS, Kattouf N, Stewart IJ, et al. Plasma for prevention and treatment of glycocalyx degradation in trauma and sepsis. Critical Care, 2024, 28(1): 254.
48. Reitsma S, Slaaf DW, Vink H, et al. The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch, 2007, 454(3): 345-359.
49. Ali FF, Mohammed MM, Hussein Y, et al. Targeting PI3K/p-Akt/eNOS, Nrf2/HO-1, and NF-κB/p53 signaling pathways by angiotensin 1-7 protects against liver injury induced by ischemia-reperfusion in rats. Cell Biochem Funct, 2024, 42(1): e3938.
50. Han S, Lee SJ, Kim KE, et al. Amelioration of sepsis by TIE2 activation-induced vascular protection. Sci Transl Med, 2016, 8(335): 335ra55.
51. Luxen M, Van Meurs M, Molema G. Unlocking the untapped potential of endothelial kinase and phosphatase involvement in sepsis for drug treatment design. Front Immunol, 2022, 13: 867625.
52. David S, Russell L, Castro P, et al. Research priorities for therapeutic plasma exchange in critically ill patients. Intensive Care Med Exp, 2023, 11(1): 26.
53. Knaup H, Stahl K, Schmidt BMW, et al. Early therapeutic plasma exchange in septic shock: a prospective open-label nonrandomized pilot study focusing on safety, hemodynamics, vascular barrier function, and biologic markers. Crit Care, 2018, 22(1): 285.
54. Iba T, Levy JH, Aihara K, et al. Newly developed recombinant antithrombin protects the endothelial glycocalyx in an endotoxin-induced rat model of sepsis. Int J Mol Sci, 2020, 22(1): 176.
55. Suzuki K, Okada H, Takemura G, et al. Recombinant thrombomodulin protects against LPS-induced acute respiratory distress syndrome via preservation of pulmonary endothelial glycocalyx. Br J Pharmacol, 2020, 177(17): 4021-4033.
56. Kikuchi K, Kazuma S, Yamakage M. Recombinant thrombomodulin and recombinant antithrombin attenuate pulmonary endothelial glycocalyx degradation and neutrophil extracellular trap formation in ventilator-induced lung injury in the context of endotoxemia. Respir Res, 2024, 25(1): 330.
57. Machin DR, Sabouri M, Zheng XY, et al. Therapeutic strategies targeting the endothelial glycocalyx. Curr Opin Clin Nutr Metab Care, 2023, 26(6): 543-550.
58. Masola V, Onisto M, Zaza G, et al. A new mechanism of action of sulodexide in diabetic nephropathy: inhibits heparanase-1 and prevents FGF-2-induced renal epithelial-mesenchymal transition. J Transl Med, 2012, 10: 213.
59. Ying J, Zhang C, Wang Y, et al. Sulodexide improves vascular permeability via glycocalyx remodelling in endothelial cells during sepsis. Front Immunol, 2023, 14: 1172892.
60. 劉瓊, 王金榮, 崔朝勃. 氫化可的松、維生素C和維生素B1聯合治療膿毒癥研究進展. 中國呼吸與危重監護雜志, 2021, 20(5): 366-371.
61. Pietrasanta C, Pugni L, Ronchi A, et al. Vascular endothelium in neonatal sepsis: basic mechanisms and translational opportunities. Front Pediatr, 2019, 7: 340.
62. Chappell D, Jacob M, Hofmann-Kiefer K, et al. Hydrocortisone preserves the vascular barrier by protecting the endothelial glycocalyx. Anesthesiology, 2007, 107(5): 776-784.

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保護與重建內皮糖萼：膿毒癥治療新靶點

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