Современные методы лечения ишемического/реперфузионного повреждения почечного аллотрансплантата


А.В. Ватазин, И.В. Нестеренко, А.Б. Зулькарнаев, Н.Л. Шахов

ГБУЗ МО «Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского», Москва
Ишемическое и реперфузионное повреждения являются сложным многофакторным процессом, повреждающим почечный трансплантат. Понимание патогенетических механизмов ишемического и реперфузионного повреждения позволяет применять различные биологические агенты для ослабления данного патологического процесса. Однако, к сожалению, использование большинства биологических агентов изучается пока еще в экспериментальных условиях и не применяется в широкой клинической практике. Цель данного обзора – показать две основные стратегии (пред- и посттрансплантационную), грамотное использование которых позволяет снижать тяжесть ишемического и реперфузионного повреждения.

Литература


1. Jamieson R.W., Friend P.J. Organ reperfusion and preservation // Front. Biosci. – 2008. – Vol. 13. – P. 221–235.
2. Bouma H.R., Ketelaar M.E., Yard B.A., et al. AMP-activated protein kinase as a target for preconditioning in transplantation medicine // Transplantation. –
2010. – Vol. 90(4). – P. 353–358.
3. Vassalli G., Milano G., Moccetti T. Role of Mitogen-Activated Protein Kinases in Myocardial Ischemia-Reperfusion Injury during Heart Transplantation // J. Transplant. – 2012. – Vol. 2012. – P. 928–954.
4. Lutz J., Thürmel K., Heemann U. Anti-inflammatory treatment strategies for ischemia/reperfusion injury in transplantation // J. Inflamm. (Lond). – 2010. –
Vol. 28(7). – P. 27.
5. Schnuelle P., Gottmann U., Hoeger S. et al. Effects of donor pretreatment with dopamine on graft function after kidney transplantation: a randomized controlled trial // JAMA. – 2009. – Vol. 302. – P. 1067–1075.
6. Benck U., Hoeger S., Brinkkoetter P.T. et al. Effects of donor pre-treatment with dopamine on survival after heart transplantation: a cohort study of heart transplant recipients nested in a randomized controlled multicenter trial // J. Am. Coll. Cardiol. – 2011. – Vol. 58(17). – P. 1768–1777.
7. Moers C., Smits J.M., Maathuis M.H. et al. Machine perfusion or cold storage in deceased-donor kidney transplantation // N. Engl. J. Med. – 2009. – Vol. 360. – P. 7–19.
8. Vaziri N., Thuillier R., Favreau F.D. et al. Analysis of machine perfusion benefits in kidney grafts: a preclinical study // J. Transl. Med. – 2011. – Vol. 9. – P. 15.
9. Olschewski P., Gass P., Ariyakhagorn V. et al. The influence of storage temperature during machine perfusion on preservation quality of marginal donor livers // Cryobiology. – 2010. – Vol. 60(3). – P. 337–343.
10. La Manna G., Conte D., Cappuccilli M.L. et al. An in vivo autotransplant model of renal preservation: cold storage versus machine perfusion in the prevention of ischemia/reperfusion injury // Artif. Organs. – 2009. – Vol. 33(7). – P. 565–570.
11. Bathini V., McGregor T., McAlister V.C. et al. Renal perfusion pump vs cold storage for donation after cardiac death kidneys: a systematic review // J. Urol. – 2013. – Vol. 189(6). – P. 2214–2220.
12. Vogel T., Brockmann J.G., Coussios C. et. al. The role of normothermic extracorporeal perfusion in minimizing ischemia reperfusion injury // Transplant. Rev. (Orlando). – 2012. – Vol. 26(2). – P. 156–162.
13. Thuillier R., Allain G., Celhay O. et al. Benefits of active oxygenation during hypothermic machine perfusion of kidneys in a preclinical model of deceased after cardiac death donors // J. Surg. Res. – 2013. – Vol. 184(2). –
P. 1174–1181.
14. Furuichi K., Wada T., Kaneko S. et al. Roles of chemokines in renal ischemia/reperfusion injury // Front. Biosci. – 2008. – Vol. 13. – P. 4021–4028.
15. Chung A.C., Lan H.Y. Chemokines in renal injury // J. Am. Soc. Nephrol. – 2011. – Vol. 22(5). – P. 802–809.
16. Lo D.J., Weaver T.A., Kleiner D.E. et al. Chemokines and their receptors in human renal allotransplantation // Transplantation. – 2011. – Vol. 91(1). – P. 70–77.
17. Stroo I., Stokman G., Gwen J. Chemokine expression in renal ischemia/reperfusion injury is most profound during the reparative phase // Int. Immunol. – 2010. – Vol. 22(6). – P. 433–442.
18. Jaswal J.S., Gandhi M., Finegan B.A. et al. Inhibition of p38 MAPK and AMPK restores adenosine-induced cardio protection in hearts stressed by antecedent ischemia by altering glucose utilization // Am. J. Physiol. Heart Circ. Physiol. –
2007. – Vol. 293. – P. H1107–1114.
19. Ashraf M., Ebner M., Wallner C. et al. A p38MAPK/MK2 signaling pathway leading to redox stress, cell death and ischemia/reperfusion injury // Cell Commun. Signal. – 2014. – Vol. 12. – P. 6.
20. Kanellis J., Ma F.Y., Kandane-Rathnayake R. et al. JNK signalling in human and experimental renal ischaemia/reperfusion injury // Nephrol. Dial. Transplant. – 2010. – Vol. 25(9). – P. 2898–2908.
21. Schenk A.D., Rosenblum J.M., Fairchild R.L. Chemokine-Directed Strategies to Attenuate Allograft Rejection // Clin. Lab. Med. – 2008. – Vol. 28(3). –
P. 441–447.
22. Furuichi K., Gao J.L., Horuk R. et al. Chemokine Receptor CCR1 Regulates Inflammatory Cell Infiltration after Renal Ischemia-Reperfusion Injury. (ed) // J. Immunol. – 2008. – Vol. 181(12). – P. 8670–8676.
23. Bennett L., Fox J., Signoret N. Mechanisms regulating chemokine receptor activity // Immunology. – 2011. – Vol. 134(3). – P. 246–256.
24. Blanchet X., Langer M., Weber C. et al. Touch of Chemokines // Front. Immunol. – 2012. – Vol. 3. – P. 175.
25. Wanderer A.A. Ischemia-reperfusion syndromes: biochemical and immunologic rationale for IL-1 targeted therapy // Clin. Immunol. – 2008. – Vol. 128. –
P. 127–132.
26. Dinarello C.A., Simon A., van der Meer J.W. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases // Nat. Rev. Drug Discovery. – 2012. – Vol. 11(8). – P. 633–652.
27. Rusai K., Huang H., Sayed N. et. al. Administration of interleukin-1 receptor antagonist ameliorates renal ischemia-reperfusion injury // Transpl. Int. – 2008. – Vol. 21. – P. 572–580.
28. Wanderer A.A. Rationale and timeliness for IL-1beta-targeted therapy to reduce allogeneic organ injury at procurement and to diminish risk of rejection after transplantation // Clin. Transplant. – 2010. – Vol. 24(3). – P. 307–311.
29. Rider P., Carmi Y., Guttman O. et al. IL-1α and IL-1β recruit different myeloid cells and promote different stages of sterile inflammation // J. Immunol. –
2011. – Vol. 187(9). – P. 4835–4843.
30. Camporeale A., Poli V. IL-6, IL-17 and STAT3: a holy trinity in auto-immunity? // Front. Biosci. – 2012. – Vol. 17. – P. 2306–2326.
31. Nechemia-Arbely Y., Barkan D., Pizov G. et al. IL-6/IL- 6R axis plays a critical role in acute kidney injury // J. Am. Soc. Nephrol. – 2008. – Vol. 19(6). – P. 1106–1115.
32. Patel N.S., Chatterjee P.K., Di Paola R. et al. Endogenous interleukin-6 enhances the renal injury, dysfunction, and inflammation caused by ischemia/reperfusion // J. Pharmacol. Exp. Ther. – 2005. – Vol. 312(3). – P. 1170–1178.
33. Chen J., Hartono J.R., John R. et al. Early interleukin 6 production by leukocytes during ischemic acute kidney injury is regulated by TLR4 // Kidney Int. – 2011. – Vol. 80(5). – P. 504–515.
34. Saraiva M., O'Garra A. The regulation of IL-10 production by immune cells // Nat. Rev. Immunol. – 2010. – Vol. 10(3). – P. 170–181.
35. Gautam S., Karen M., Dan B. et al. Interleukin 10 knockout frail mice develop cardiac and vascular dysfunction with increased age // J. Experim. Gerontol. – 2013. – Vol. 48(2). – P. 128–135.
36. Hammer M., Mages J. Control of dual-specificity phosphatase-1 expression in activated macrophages by IL-10 // Eur. J. Immunol. – 2010. – Vol. 35(10). –
P. 2991–3001.
37. Lawson C., Wolf S. ICAM-1 signaling in endothelial cells // Pharmacol. Rep. –
2009. – Vol. 61(1). – P. 22–32.
38. Marwa E., Sabbahy and Vishal S. Ischemic kidney injury and mechanisms of tissue repair // Wiley Interdiscip. Rev. Syst. Biol. Med. – 2011. – Vol. 3(5). – P. 606–618.
39. Kalogeris T., Baines C.P., Krenz M. et al. Cell Biology of Ischemia/Reperfusion Injury // Int. Rev. Cell Mol. Biol. – 2012. – Vol. 298. –
P. 229–317.
40. Vincenti F., Mendez R., Pescovitz M. et al. A phase I/II randomized open-label multicenter trial of efalizumab, a humanized anti-CD11a, anti-LFA-1 in renal transplantation // Am. J. Transplant. – 2007. – Vol. 7. – P. 1770–1777.
41. Goto R., Issa F., Heidt S. et al. Ischemia-Reperfusion Injury Accelerates Human Antibody-Mediated Transplant Vasculopathy // Transplantation. – 2013. – Vol. 96(2). – P. 139–145.
42. Beiras-Fernandez A., Chappell D., Hammer C. et al. Impact of polyclonal anti-thymocyte globulins on the expression of adhesion and inflammation molecules after ischemia-reperfusion injury // Transpl. Immunol. – 2009. – Vol. 20(4). – P. 224–228.
43. Latanich C.A., Toledo-Pereyra L.H. Searching for NF-kappaB-based treatments of ischemia reperfusion injury // J. Invest. Surg. – 2009. – Vol. 22. – P. 301–315.
44. Gu J.H., Ge J.B., Li M. et al. Inhibition of NF-κB activation is associated with anti-inflammatory and anti-apoptotic effects of Ginkgolide B in a mouse model of cerebral ischemia/reperfusion injury // Eur. J. Pharm. Sci. – 2012. – Vol. 47(4). – P. 652–660.
45. Padrissa-Altés S., Zaouali M.A., Bartrons R. et al. Ubiquitin-proteasome system inhibitors and AMPK regulation in hepatic cold ischemia and reperfusion injury: possible mechanisms // Clin. Sci. (Lond). – 2012. – Vol. 123(2). –
P. 93–98.
46. Ahmadiasl N., Banaei S., Alihemmati A. Combination antioxidant effect of erythropoietin and melatonin on renal ischemia-reperfusion injury in rats // Iran J. Basic. Med. Sci. – 2013. – Vol. 16(12). – P. 1209–1216.
47. Amura C.R., Renner B., Lyubchenko T. Complement Activation and Toll-Like Receptor-2 Signaling Contribute to Cytokine Production after Renal Ischemia/Reperfusion // Mol. Immunol. – 2012. – Vol. 52(3–4). –
P. 249–257.
48. Rusai K., Sollinger D., Baumann M. et al. Toll-like receptors 2 and 4 in renal ischemia/reperfusion injury // Pediatr. Nephrol. – 2010. – Vol. 25. –
P. 853–860.
49. Kruger B., Krick S., Dhillon N. et al. Donor Toll-like receptor 4 contributes to ischemia and reperfusion injury following human kidney transplantation // Proc. Natl. Acad. Sci USA. – 2009. – Vol. 106. – P. 3390–3395.
50. Jang H.R., Ko G.J., Wasowska B.A. et al. The interaction between ischemia-reperfusion and immune responses in the kidney // J. Mol. Med. – 2009. – Vol. 87. – P. 859–864.
51. Diepenhorst G.M., van Gulik T.M., Hack C.E. Complement-mediated ischemia-reperfusion injury: lessons learned from animal and clinical studies // Ann. Surg. – 2009. – Vol. 249. – P. 889–899.
52. Zheng X., Zhang X., Feng B. et al. Gene silencing of complement C5a receptor using siRNA for preventing ischemia/reperfusion injury // Am. J. Pathol. – 2008. – Vol. 173. – P. 973–980.
53. Damman J., Daha M.R., van Son W.J. et al. Crosstalk between complement and Toll-like receptor activation in relation to donor brain death and renal ischemia-reperfusion injury // Am. J. Transplant. – 2011. – Vol. 11(4). –
P. 660–669.
54. Damman J., Nijboer W.N., Schuurs T.A. et al. Local renal complement C3 induction by donor brain death is associated with reduced renal allograft function after transplantation // Nephrol. Dial. Transplant. – 2011. – Vol. 26(7). – P. 2345–2354.
55. Ferraresso M., Macor P., Valente M. et al. Posttransplant ischemiareperfusion injury in transplanted heart is prevented by a minibody to the fifth component of complement // Transplantation. – 2008. – Vol. 86. – P. 1445–1451.
56. Woodruff T.M., Nandakumar K.S., Tedesco F. Inhibiting the C5-C5a receptor axis // Mol. Immunol. – 2011. – Vol. 48(14). – P. 1631–1642.
57. Wang D.S., Li Y., Dou K.F. et al. Utility of adenovirus-mediated Fas ligand and bcl-2 gene transfer to modulate rat liver allograft survival // Hepatobiliary Pancreat. Dis. Int. – 2006. – Vol. 5. – P. 505–510.
58. Yeom H.J., Koo O.J., Yang J. et al. Generation and characterization of human heme oxygenase-1 transgenic pigs // PLoS One. – 2012. – Vol. 7(10). –
P. e46646.
59. Wu J., Hecker J.G., Chiamvimonvat N. Antioxidant Enzyme Gene Transfer for Ischemic Diseases // Adv. Drug Deliv. Rev. – 2009. – Vol. 61(4). –
P. 351–363.
60. Oh Y.B., Ahn M., Lee S.M. et al. Inhibition of Janus activated kinase-3 protects against myocardial ischemia and reperfusion injury in mice // Exp. Mol. Med. – 2013. – Vol. 45. – P. e23.
61. Lin M., Li L., Pokhrel G. et al. The protective effect of baicalin against renal ischemia-reperfusion injury through inhibition of inflammation and apoptosis // BMC Complement Altern. Med. – 2014. – Vol. 14. – P. 19.
62. Pereira B.J., Castro I., Burdmann E.A. et al. Effects of sirolimus alone or in combination with cyclosporine A on renal ischemia/reperfusion injury // Braz. J. Med. Biol. Res. – 2010. – Vol. 43(8). – P. 737–744.
63. Chen G., Chen H., Wang C. et al. Rapamycin ameliorates kidney fibrosis by inhibiting the activation of mTOR signaling in interstitial macrophages and myofibroblasts // PLoS One. – 2012. – Vol. 7(3). – P. e33626.
64. Kezic A., Becker J.U., Thaiss F. The Effect of mTOR-Inhibition on NF-kB Activity in Kidney Ischemia-Reperfusion Injury in Mice // Transplant. Proc. – 2013. – Vol. 45. – P. 1708–1714.
65. Coornaert B., Carpentier I., Beyaert R. A20: central gatekeeper in inflammation and immunity // J. Biol. Chem. – 2009. – Vol. 284. – P. 8217–8221.
66. Vereecke L., Beyaert R., van Loo G. The ubiquitin-editing enzyme A20 (TNFAIP3) is a central regulator of immunopathology // Trends Immunol. – 2009. – Vol. 30(8). – P. 383–391.
67. Lutz J., Luong le A., Strobl M. et al. The A20 gene protects kidneys from ischaemia/reperfusion injury by suppressing pro-inflammatory activation // J. Mol. Med. – 2008. – Vol. 86. – P. 1329–1339.
68. Prasad A.S., Bao B., Beck F.W. et al. Zinc-suppressed inflammatory cytokines by induction of A20-mediated inhibition of nuclear factor-κB // Nutrition. – 2011. – Vol. 27(7–8). – P. 816–823.
69. Xu M.Q., Yan L.N., Gou X.H. et al. Zinc finger protein A20 promotes regeneration of small-for-size liver allograft and suppresses rejection and results in a longer survival in recipient rats // J. Surg. Res. – 2009. – Vol. 152. –
P. 35–45.
70. Kunugi S., Shimizu A., Kuwahara N. et al. Inhibition of matrix metalloproteinases reduces ischemia-reperfusion acute kidney injury // Lab. Invest. – 2011. – Vol. 91(2). – P. 170–180.
71. Tan R.J., Liu Y. Matrix metalloproteinases in kidney homeostasis and diseases // Am. J. Physiol. Renal Physiol. – 2012. – Vol. 302(11). – P. 351–361.
72. Lutz J., Yao Y., Song E. et al. Inhibition of matrix metalloproteinases during chronic allograft nephropathy in rats // Transplantation. – 2005. – Vol. 79. – P. 655–661.
73. Bajwa A., Kinsey G.R., Okusa M.D. Immune Mechanisms and Novel Pharmacological Therapies of Acute Kidney Injury // Curr. Drug Targets. – 2009. – Vol. 10(12). – P. 1196–1204.
74. Chen T.H., Liao F.T., Yang Y.C. et al. Inhibition of inducible nitric oxide synthase ameliorates myocardial ischemia/reperfusion injury - induced acute renal injury // Transplant Proc. – 2014. – Vol. 46(4). – P. 1123–1126.
75. Guz G., Demirogullari B., Ulusu N.N. et al. Stobadine protects rat kidney against ischaemia/reperfusion injury // Clin. Exp. Pharmacol. Physiol. – 2007. – Vol. 34. – P. 210–216.
76. Yildiz F., Coban S., Terzi A. et al. Protective effects of Nigella sativa against ischemia-reperfusion injury of kidneys // Ren. Fail. – 2010. – Vol. 32(1). –
P. 126–131.
77. Sharfuddin A.A., Sandoval R.M., Berg D.T. et al. Soluble thrombomodulin protects ischemic kidneys // J. Am. Soc. Nephrol. – 2009. – Vol. 20. –
P. 524–534.
78. Zhang G., Zou X., Miao S. et al. The anti-oxidative role of Micro-vesicles derived from human Wharton-Jelly mesenchymal stromal cells through NOX2/gp91(phox) suppression in alleviating renal ischemia-reperfusion injury in rats // PLoS One. – 2014. – Vol. 9(3). – P. e92129.
79. Gatti S., Bruno S., Deregibus MC. et al. Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury // Nephrol. Dial. Transplant. – 2011. – Vol. 26(5). – P. 1474–1483.
80. Du T., Cheng J., Zhong L. et al. The alleviation of acute and chronic kidney injury by human Wharton's jelly-derived mesenchymal stromal cells triggered by ischemia-reperfusion injury via an endocrine mechanism // Cytotherapy. – 2012. – Vol. 14(10). – P. 1215–1227.
81. Zou X., Zhang G., Cheng Z. et al. Microvesicles derived from human Wharton's Jelly mesenchymal stromal cells ameliorates renal ischemia-reperfusion injury in rats by suppressing CX3CL1 // Stem. Cell Res. Ther. – 2014. – Vol. 5(2). – P. 40.
82. Kostapanos M.S., Liberopoulos E.N., Elisaf M.S. Statin pleiotropy against renal injury // J. Cardiometab. Syndr. – 2009. – Vol. 4(1). – P. E4–9.
83. Sharyo S., Yokota-Ikeda N., Mori M. et al. Pravastatin improves renal ischemia-reperfusion injury by inhibiting the mevalonate pathway // Kidney Int. – 2008. – Vol. 74. – P. 577–584.
84. Brunelli S.M., Waikar S.S., Bateman B.T. et al. Preoperative statin use and postoperative acute kidney injury // Am. J. Med. – 2012. – Vol. 125(12). –
P. 1195–1204.
85. Caetano A.M., Vianna Filho P.T., Castiglia Y.M. et al. Erythropoietin attenuates apoptosis after ischemia-reperfusion-induced renal injury in transiently hyperglycemic Wister rats // Transplant Proc. – 2011. – P. 43(10). –
Vol. 3618–3621.
86. Hu L., Yang C., Zhao T. et al. Erythropoietin ameliorates renal ischemia and reperfusion injury via inhibiting tubulointerstitial inflammation // J. Surg. Res. –
2012. – Vol. 176(1). – P. 260–266.
87. Ardalan M.R., Estakhri R., Hajipour B. et al. Erythropoietin ameliorates oxidative stress and tissue injury following renal ischemia/reperfusion in rat kidney and lung // Med. Princ. Pract. – 2013. – Vol. 22(1). – P. 70–74.
88. Simmons M.N., Subramanian V., Crouzet S., et al. Alpha-melanocyte stimulating hormone analogue AP214 protects against ischemia induced acute kidney injury in a porcine surgical model // J. Urol. – 2010. – Vol. 183(4). – P. 1625–1629.
89. Hussein A.A., El-Dken Z.H., Barakat N. et al. Renal ischaemia/reperfusion injury: possible role of aquaporins // Acta Physiol. (Oxf). – 2012. – Vol. 204(3). – P. 308–316.
90. Chen J., Wang W., Zhang Q. et al. Low molecular weight fucoidan against renal ischemia-reperfusion injury via inhibition of the MAPK signaling pathway // PLoS One. – 2013. – Vol. 8(2). – P. e56224.
91. Yuzer H., Yuzbasioglu M.F., Ciralik H. et al. Effects of intravenous anesthetics on renal ischemia/reperfusion injury // Ren. Fail. – 2009. – Vol. 31(4). –
P. 290–296.
92. Dogan Z., Yuzbasioglu M.F., Kurutas E.B. et al. Thiopental improves renal ischemia-reperfusion injury // Ren. Fail. – 2010. – Vol. 32(3). – P. 391–395.
93. Yuzbasioglu M.F., Aykas A., Kurutas E.B. et al. Protective effects of propofol against ischemia/reperfusion injury in rat kidneys // Ren. Fail. – 2010. – Vol. 32(5). – P. 578–583.
94. Yang S., Chou W.P., Pei L. Effects of propofol on renal ischemia/reperfusion injury in rats // Exp. Ther. Med. – 2013. – Vol. 6(5). – P. 1177–1183.
95. Lee Y.M., Shin J.W., Lee E.H. et al. Protective effects of propofol against hydrogen peroxide-induced oxidative stress in human kidney proximal tubular cells // Korean J. Anesthesiol. – 2012. – Vol. 63(5). – P. 441–446.
96. Kim M., Park S.W., Kim M. et al. Isoflurane activates intestinal sphingosine kinase to protect against renal ischemia-reperfusion-induced liver and intestine injury // Anesthesiology. – 2011. – Vol. 114(2). – P. 363–373.
97. Qin Z., Lv E., Zhan L. et al. Intravenous pretreatment with emulsified isoflurane preconditioning protects kidneys against ischemia/reperfusion injury in rats // BMC Anesthesiol. – 2014. – Vol. 14. – P. 28.
98. Ozkan F., Senayli Y., Ozyurt H. et al. Antioxidant effects of propofol on tourniquet-induced ischemia-reperfusion injury: an experimental study // J. Surg. Res. – 2012. – Vol. 176(2). – P. 601–607.


Об авторах / Для корреспонденции


Информация об авторах:
Ватазин А.В. – руководитель отдела трансплантологии, нефрологии
и хирургической гемокоррекции, заведующий кафедрой трансплантологии, нефрологии и искусственных органов ГБУЗ МО МОНИКИ
им. М.Ф. Владимирского, д.м.н., профессор
Нестеренко И.В. – профессор кафедры трансплантологии, нефрологии
и искусственных органов ГБУЗ МО МОНИКИ им. М.Ф. Владимирского, д.м.н.
Зулькарнаев А.Б. – доцент кафедры трансплантологии, нефрологии и искусственных органов ГБУЗ МО МОНИКИ им. М.Ф. Владимирского, к.м.н.
Шахов Н.Л. – аспирант кафедры трансплантологии, нефрологии
и искусственных органов ГБУЗ МО МОНИКИ им. М.Ф. Владимирского;
е-mail: Nick-graft@rambler.ru


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