Экспериментальные модели острого почечного повреждения

Для изучения патогенетических механизмов острого почечного повреждения (ОПП) различной этиологии и оценки эффективности нефропротективных мероприятий было разработано значительное количество экспериментальных работ на животных, которые воссоздают клиническое течение различных форм почечной недостаточности. Детальное описание имеющихся моделей ОПП у животных позволит понять специфику проведения конкретного эксперимента и правильно интерпретировать полученные результаты. Введение глицерина индуцирует повреждение почек, которое возникает при рабдомиолизе. Использование в эксперименте лекарственных средств таких, как гентамицин, цисплатин, ифосфамид, диклофенак, стимулирует развитие ОПП, которое наблюдается при назначении соответствующего препарата в медицинской практике. Модель контраст-индуцированной ОПП имитирует у животных почечную недостаточность, возникающую во время ангиографических исследований с использованием радиоконтрастных веществ. Для создания модели ОПП, связанной с действием вредных факторов, распространенных в окружающей среде, используют соли урана, хрома. Почечные дисфункции, возникающие при воздействии загрязненной воды, симулируются введением нитрилотриацетата и 1,2-дихлорвинил-L-цистеина. Нарушение функции почек при генерализованной инфекции изучается на модели сепсис-индуцированной ОПП. Различные экспериментальные модели ишемически-реперфузионного (И/Р) ОПП симулируют гемодинамические нарушения, происходящие при снижение почечного кровотока. В данной работе представлен детальный протокол экспериментальной модели И/Р ОПП у крыс вследствие билатерального клипирования почечных ножек с описанием технических вопросов, возможных вариантов модели, их особенностей а также решение сложностей, которые могут встретиться во время проведения эксперимента.

1. Куценко С.А. Основы токсикологии: Учебное пособие. СП(б): Фолиант, 2004. 720 с.

2. Arany I., Safirstein R.L. Cisplatin nephrotoxicity. Semin Nephrol. 2003. 23(5): 460-464.

3. Asif A., Garces G., Preston R.A., et al. Current trials of interventions to prevent radiocontrast-induced nephropathy. Am J Ther. 2005. 12(2): 127-132.

4. Augusti P.R., Conterato G.M., Somacal S., et al. Effect of astaxanthin on kidney function impairment and oxidative stress induced by mercuric chloride in rats. Food Chem Toxicol. 2008. 46(1): 212-219.

5. Bagshaw SM. Acute kidney injury care bundles. Nephron. 2015. 13 (4): 247-251.

6. Baker RC, Armstrong MA, Young B. et al. Methylprednisolone increases urinary nitrate concentrations and reduces subclinical renal injury during infrarenal aortic ischemia reperfusion. Ann Surg. 2006. 244(5): 821-826.

7. Bhalodia Y, Kanzariya N, Patel R. et al. Renoprotective activity of benin case cerifera fruit extract on ischemia/reperfusion-induced renal damage in rat. Iran J Kidney Dis. 2009. 3(2): 80-85.

8. Blantz R.C. The mechanism of acute renal failure after uranyl nitrate. J Clin Invest. 1975. 55(3): 621-635.

9. Bulger R.E. Renal damage caused by heavy metals. Toxicol Pathol. 1986. 14(1): 58-65.

10. Chen N., Aleksa K., Woodland C., et al. N-Acetylcysteine prevents ifosfamide induced nephrotoxicity in rats. Br J Pharmacol. 2008. 153(7): 1364-1372.

11. Chen Y., Sun С., Lin Y., et al. Adipose-derived mesenchymal stem cells protects kidneys against ischemia-reperfusion injury through suppressing oxidative stress and inflammatory reaction. J Tranplant Med. 2011. 5(9): 51-70.

12. Chertow G.M, Levy E.M, Hammermeister K.E, et al. Independent association between acute renal failure and mortality following cardiac surgery. Am J Med. 1998. 104(5): 343-348.

13. Dai R, Dheen S.T, Tay S.S. Induction of cytokine expression in rat post-ischemic sinoatrial node (SAN). Cell Tissue Res. 2002. 310(1): 59-66.

14. Darnerud P.O., Brandt I., Feil V.J., et al. S-(1,2-dichlorovinyl-L-cysteine (DCVC) in the mouse kidney: correlation between tissue-binding and toxicity. Toxicol Appl Pharmacol. 1988. 95(3): 423-434.

15. Damianovich M, Ziv I, Heyman SN. ApoSence: a novel technology for functional molecular imaging of cell death in models of acute renal tubular necrosis. Eur J Nucl Med Mol Imaging. 2006. 33(3): 281-291.

16. De-Rosa C.T., Johnson B.L., Fay M., et al. Public health implications hazardous waste sites: findings, assessment and research. Food Chem Toxicol. 1996. 34(11): 1131-1138.

17. Domingo J.L. Chemical toxicity of uranium. Toxic Ecotoxic News. 1995. 2(1): 74-78.

18. Efrati S., Berman S., Siman-Tov Y., et al. N-acetylcysteine attenuates NSAID induced rat renal failure by restoring intrarenal prostaglandin synthesis. Nephrol Dial Transplant. 2007. 22(7): 1873-1881.

19. Erdem A., Gundogan N.U., Usubutun A., et al. The protective effect of taurine against gentamicin-induced acute tubular necrosis in rats. Nephrol Dial Transplant. 2000. 15(8): 1175-1182.

20. Ewald K.A., Calabrese E.J. Lead reduces the nephrotoxicity of mercuric chloride. Ecotoxicol Environ Saf. 2001. 48(2): 215-218.

21. Ferrari S., Pieretti F., Verri E., et al. Prospective evaluation of renal function in pediatric and adult patients treated with high-dose ifosfamide, cisplatin and high-dose methotrexate. Anticancer Drugs. 2005. 16(7): 733-738.

22. Foglieni C, Fulgenzi A, Ticozzi P. et al. Protective effect of EDTA preadministration on renal ischemia. BMC Nephrol. 2006. 15(7):5-16.

23. Ghosh J., Das J., Manna P., et al. Acetaminophen induced renal injury via oxidative stress and TNF-a production: therapeutic potential of arjunolic acid. Toxicology. 2010. 268(1): 8-18.

24. Hamazaki S., Okada S., Ebina Y., et al. Acute renal failure and glucosuria induced by ferric nitrilotriacetate in rats. Toxicol Appl Pharmacol. 1985. 77(2): 267-274.

25. Helmholz H.F. Renal changes in the rabbit resulting from intravenous injection of hypertonic solution of sucrose. J Pediat. 1933. 3(1): 144-157.

26. Hengy B., Hayi-Slayman D., Page M., et al. Acute renal failure after acetaminophen poisoning: report of three cases. Can J Anaesth. 2009. 56(10): 770-774.

27. Heyman S.N., Lieberthal W., Rogiers P., et al. Animal models of acute tubular necrosis. Curr Opin Crit Care. 2002. 8(6): 526-534.

28. Honore PM, Jacobs R, Hendricks I, et al. Prevention and treatment of sepsis-induced acute kidney injury: an update. Ann Intensive Care. 2015 Dec. 5(1): 51-61.

29. Hu J., Zhang L., Wang N., et al. Mesenchemal stem cells attenuate ischemic acute kidney injury by inducing regulatory T cells through splenocyte interactions. Kidney Int. 2013. 84 (3): 521-531.

30. Humes H.D., Sastrasinh M., Weinberg J.M. Calcium is a competitive inhibitor of gentamicin-renal membrane binding interactions and dietary calcium supplementation protects against gentamicin nephrotoxicity. J Clin Invest. 1984. 73(1): 134-147.

31. Inoue M., Akimoto T., Saito O., et al. Successful relatively low-dose corticosteroid therapy for diclofenac induced acute interstitial nephritis with severe renal failure. Clin Exp Nephrol. 2008. 12(4): 296-299.

32. Jacob R. Acute renal failure. Indian J Anaesth. 2003. 47(5): 367-372.

33. Jesmin S., Gando S., Zaedi S., et al. Protease-activated receptor 2 blocking peptide counteracts endotoxininduced inflammation and coagulation and ameliorates renal fibrin deposition in a rat model of acute renal failure. Shock. 2009. 32(6): 626-632.

34. Khan M.R., Siddiqui S., Parveen K., et al. Nephroprotective action of tocotrienol-rich fraction (TRF) from palm oil against potassium dichromate (K2Cr2O7)-induced acute renal injury in rats. Chem Biol Interact. 2010. 186(2): 228-238.

35. Kusaka J., Koga H., Hagiwara S. et al. Age-dependent responses to renal ischemia-reperfusion injury. J Surg Res. 2012. 172 (1): 153-158.

36. Lameire N., Van Biesen W., Vanholder R. The changing epidemiology of acute renal failure. Nat Clin Pract Nephrol. 2006. 2(8): 64-377.

37. Lee H.T., Jan M., Bae S.C., et al. A1 adenosine receptor knockout mice are protected against acute radiocontrast nephropathy in vivo. Am J Physiol Renal Physiol. 2006. 290 (6): 1367-1375.

38. Lieberthal W, Levine JS. Mechanisms of apoptosis and its potential role in renal tubular epithelial cell injury. Am J Physiol. 1996. 271(3): 477-488.

39. Lock E.A., Ishmael J. The acute toxic effects of paraquat and diquat on the rat kidney. Toxicol Appl Pharmacol. 1979. 50(1): 67-76.

40. Massermann J.H. Effects of the intravenous administration of hypertonic solution of sucrose with special reference to cerebrospinal fluid pressure. Bull Johns Hopkins Hosp. 1935. 57(20): 12-17.

41. Mathew T.H. Drug-induced renal disease. Med J Aust. 1992. 156(10): 724-728.

42. Matthijsen RA, Huugen D, Hoebers NT. et al. Myeloperoxidase is critically involved in the induction of organ damage after renal ischemia reperfusion. Am J Pathol. 2007. 171(6): 1743-1752.

43. McWhinnie D.L. Morphometric analysis of cellular infiltration assessed by monoclonal antibody labeling in sequential human renal allograft biopsies. Transplantation. 1986. 42 (4): 352-358.

44. Mitazaki S, Kato N, Suto M, et al. Interleukin-6 deficiency accelerates cisplatin-induced acute renal failure but not systemic injury. Toxicology. 2009. 265(3): 115-121.

45. Mullin E.M., Bonar R.A., Paulson D.F. Acute tubular necrosis. An experimental model detailing the biochemical events accompanying renal injury and recovery. Invest Urol. 1976. 13(4): 289-294.

46. Mwengee W., Butler T., Mgema S., et al. Treatment of plague with gentamicin or doxycycline in a randomized clinical trial in Tanzania. Clin Infect Dis. 2006. 42(5): 614-621.

47. Nakamura A., Niimi R., Yanagawa Y. Protection from sepsis-induced acute renal failure by adenoviral-mediated gene transfer of β2-adrenoreceptor. Nephrol Dial Transplant. 2010. 25(3): 730-737.

48. Palani S., Kumar R.P., Kumar B.S. Effect of the ethanolic extract of Indigofera barberi (L.) in acute acetaminophen induced nephrotoxic rats. New Biotechnol. 2009. 25(Suppl. 2): 14-24.

49. Park K.M., Kim J.I., Ahn Y., et al. Testosterone is responsible for enhanced susceptibility of males to ischemic renal injury. J Biol Chem. 2004. 279(50): 52282-52292.

50. Rosen S., Neyman S.N. Difficulties in understanding human “acute tubular necrosis”: limited data and flawed animal models. Kidney Int. 2001. 60(4): 1220-1224.

51. Ruetten H., Thiemermann C., Vane J.R. Effects of the endothelin receptor antagonist, SB 209670, on circulatory failure and organ injury in endotoxic shock in the anaesthetized rat. Br J Pharmacol. 1996. 118(1): 198-204.

52. Selby N.M., Shaw S., Woodier N., et al. Gentamicin-associated acute kidney injury. Q J Med. 2009. 102(12): 873-880.

53. Shanley P.F., Rosen M.D., Brezis M. et al. Topography of focal proximal tubular necrosis after ischemia with reflow in the rat kidney. Am J Patho. 1986. 122(3): 462-468.

54. Singh A.P., Muthuraman A., Jaggi A.S., et al. Animal model of acute renal failure. Pharmacological Reports. 2012. 64 (21): 31-44.

55. Stevens P.E., Tamimi W.A., Al - Hosani M.K., et al. Non - special management of acute renal failure. QJM. 2011. 94(10): 533-540.

56. Thiel G., Wilson D.R., Arce M.L., et al. Glycerol induced hemoglobinuric acute renal failure in the rat. Nephron. 1967. 4(5): 276-297.

57. Troyer D.A., Kreisberg J.I., Venkatachalam M.A. Lipid alterations in LLC-PK1 cells exposed to mercuric chloride. Kidney Int. 1986. 29(2): 530-538.

58. Umemura T., Hasegawa R., Sai-Kato K., et al. Prevention by 2-mercaptoethane sulfonate and N-acetylcysteine of renal oxidative damage in rats treated with ferric nitrilotriacetat. Jpn J Cancer Res. 1996. 8(9): 882-886.

59. Vanholder R., Sever M.S., Erek E., et al. Rhabdomyolysis. J Am Soc Nephrol. 2000. 11(8): 1553-1561.

60. Wan B., Hao L., Qiu Y., et al. Blocking tumor necrosis factor-a inhibits folic acid-induced acute renal failure. Exp Mol Pathol, 2006. 81(3): 211-216.

61. Wei Q., Dong Z. Mouse model of ischemic acute kidney injury: technical notes and tricks. Am J Physiol Renal Physiol. 2012. 303(11): 487-494.

62. Willox J.C., McAllister E.J., Sangster G., et al. Effects of magnesium supplementation in testicular cancer patients receiving cisplatin: a randomised trial. Br J Cancer. 1986. 54(1): 19-23.

63. Yang Q., Liu D., Long Y., et al. Acute renal failure during sepsis: Potential role of cell cycle regulation. J Infect. 2009. 58(6): 459-464.

64. Yesilyurt A., Aydýn Erden I., Bilgic I., et al. The protective effect of erdosteine on radiocontrast induced nephrotoxicity in rats. Environ Toxicol. 2011. 26(4): 395-402.

65. Zager RA, Altschuld R. Body temperature: An important deterrenal of severity of ischemic renal injury. Am J Physiol. 1986. 251(1): 87-93.

66. Zhang J., Lu H. Ifosfamide induces acute renal failure via inhibition of the thioredoxin reductase activity. Free Radic Biol Med. 2007. 43(12): 1574-1583.