Моделирование синдрома системного воспалительного ответа на анестезированных крысах

Авторы

  • Вячеслав Георгиевич Александров Институт физиологии им. И. П. Павлова РАН; Российский государственный педагогический университет им. А. И. Герцена https://orcid.org/0000-0002-5079-633X
  • Елена Алексеевна Губаревич Институт физиологии им. И. П. Павлова РАН; Российский государственный педагогический университет им. А. И. Герцена https://orcid.org/0000-0003-2305-2279
  • Галина Анатольевна Данилова Институт физиологии им. И. П. Павлова РАН
  • Татьяна Сергеевна Туманова Институт физиологии им. И. П. Павлова РАН; Российский государственный педагогический университет им. А. И. Герцена https://orcid.org/0000-0001-6393-6699

DOI:

https://doi.org/10.33910/2687-1270-2020-1-1-51-60

Ключевые слова:

синдром системного воспалительного ответа, крыса, бактериальный липополисахарид, лейкоциты, нейтрофилы

Аннотация

Системное воспаление вызывает нарушение функций дыхания и кровообращения. Для экспериментального исследования механизмов этих нарушений необходимо моделировать синдром системного воспалительного ответа (ССВО) в условиях острого эксперимента на животных, анестезированных уретаном. Цель настоящей работы состояла в проверке гипотезы, согласно которой в указанных экспериментальных условиях можно воспроизвести один из симптомов ССВО, а именно — изменение количества и состава лейкоцитов крови. Работа выполнена на лабораторных крысах (самцы Вистар, вес 250–300 г), анестезированных уретаном (1600 мг/кг, в/б) и разбитых на три группы. Животные первой группы (n = 5) были подвергнуты операции, имитирующей некоторые оперативные подходы, используемые при изучении функций дыхания и кровообращения. Второй группе животных (n = 5) вводили внутривенно 500 мкг бактериального липополисахарида (ЛПС), растворенного в 1 мл физиологического раствора. В третьей группе крыс (n = 5) ложная операция сочеталась с введением ЛПС. Измерение количества лейкоцитов в образцах крови, взятых из хвостовой вены, показало, что введение ЛПС вызывало у животных второй и третьей групп снижение общего количества лейкоцитов, главным образом за счет нейтрофилов. Полученные результаты доказывают, что в условиях острого эксперимента на крысах, анестезированных уретаном, внутривенным введением ЛПС можно вызвать лейкопению, т. е. воспроизвести один из важнейших (наряду с тахикардией, тахипноэ и изменением температуры тела) симптомов ССВО.

Библиографические ссылки

ЛИТЕРАТУРА

Галкин, А. А., Демидова, В. С. (2015) Нейтрофилы и синдром системного воспалительного ответа. Раны и раневые инфекции. Журнал имени проф. Б. М. Костючёнка, т. 2, № 2, с. 25–31. DOI: 10.17650/2408-9613-2015-2-2-25-31

Гельфанд, Б. Р., Салтанов, А. И. (ред.) (2009) Интенсивная терапия: национальное руководство: в 2 т. Т. 1. М.: ГЭОТАР-Медиа, 955 с.

Межирова, Н. М., Данилова В. В., Овчаренко, С. С. (2011) Патофизиологические и диагностические аспекты синдрома системного воспалительного ответа. Медицина неотложных состояний, № 1–2, с. 34–40.

Симбирцев, А. С., Тотолян, А. А. (2015) Цитокины в лабораторной диагностике. Инфекционные болезни, № 2, с. 82–98.

Туманова, Т. С., Александров, В. Г. (2016) Влияние бактериального липополисахарида на рефлекторные механизмы кардиореспираторной системы анестезированной крысы. В кн.: А. И. Григорьев, Ю. В. Наточин, Р. И. Сепиашвили и др. (ред.). Научные труды V Съезда физиологов СНГ, V Съезда биохимиков России, Конференции ADFLIM. Сочи: б. и., с. 158. (Acta Naturae. Спецвыпуск: в 2 т. Т. 1.)

Черешнев, В. А., Гусев, Е. Ю. (2002) Системное воспаление как иммунопатобиологический феномен. Цитокины и воспаление, т. 1, № 2, с. 17.

Черешнев, В. А., Шилов, М И., Черешнева М. В. и др. (2011) Экспериментальные модели в патологии. Пермь: Изд-во ПГНИУ, 267 с.

Altenburg, S. P., Martins, M. A., Silva, A. R. et al. (1997) LPS-induced blood neutrophilia is inhibited by alpha 1-adrenoceptor antagonists: A role for catecholamines. The Journal of Leukocyte Biology, vol. 61, no. 6, pp. 689–694. PMID: 9201259. DOI: 10.1002/jlb.61.6.689 (In English)

Beck-Schimmer, B., Baumann, L., Restin, T. et al. (2017) Sevoflurane attenuates systemic inflammation compared with propofol, but does not modulate neuro-inflammation: A laboratory rat study. European Journal of Anaesthesiology, vol. 34, no. 11, pp. 764–775. PMID: 28759530. DOI: 10.1097/EJA.0000000000000668 (In English)

Benveniste, E. N. (1998) Cytokine actions in the central nervous system. Cytokine & Growth Factors Reviews, vol. 9, no. 3–4, pp. 259–275. PMID: 9918124. DOI: 10.1016/S1359-6101(98)00015-X (In English)

Black, P. H. (1994) Immune system-central nervous system interactions: Effect and immunomodulatory consequences of immune system mediators on the brain. Antimicrobial Agents and Chemotherapy, vol. 38, no. 1, pp. 7–12. PMID: 8141583. DOI: 10.1128/AAC.38.1.7 (In English)

Bone, R. C. (1996) Toward a theory regarding the pathogenesis of the systemic inflammatory response syndrome: What we do and do not know about cytokine regulation. Critical Care Medicine, vol. 24, no. 1, pp. 163–172. PMID: 8565523. DOI: 10.1097/00003246-199601000-00026 (In English)

Bone, R. C., Balk, R. A., Cerra, F. B. et al. (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest, vol. 101, no. 6, pp. 1644–1655. PMID: 1303622. DOI: 10.1378/chest.101.6.1644 (In English)

Cao, C., Matsumura, K., Yamagata, K., Watanabe, Y. (1997) Involvement of cyclooxygenase-2 in LPS-induced fever and regulation of its mRNA by LPS in the rat brain. American Journal of Physiology, vol. 272, no. 6, pt. 2, pp. R1712–R1725. PMID: 9227582. DOI: 10.1152/ajpregu.1997.272.6.R1712 (In English)

Castro-Faria-Neto, H. C., Penido, C. M., Larangeira, A. P. et al. (1997) A role for limphocytes and cytokines on the eosinophil migration induced by LPS. Memórias do Instituto Oswaldo Cruz, vol. 92, suppl. II, pp. 197–200. PMID: 9698933. DOI: 10.1590/s0074-02761997000800026 (In English)

Feuerstein, G., Hallenbeck, J. M., Vanatta, B. et al. (1990) Effect of gram-negative endotoxin on levels of serum corticosterone, TNF alpha, circulating blood cells, and the survival of rats. Circulatory Shock, vol. 30, no. 3, pp. 265–78. PMID: 2178800. (In English)

Garami, A., Steiner, A. A., Romanovsky, A. A. (2018) Fever and hypothermia in systemic inflammation. Handbook of Clinical Neurology, vol. 157, pp. 565–597. PMID: 30459026. DOI: 10.1016/B978-0-444-64074-1.00034-3 (In English)

Herzum, I., Renz, H. (2008) Inflammatory markers in SIRS, sepsis and septic shock. Current Medicinal Chemistry, vol. 15, no. 6, pp. 581–587. PMID: 18336272. DOI: 10.2174/092986708783769704 (In English)

Kao, S. J., Wang, D., Lin, H. I., Chen, H. I. (2006) N-acetylcysteine abrogates acute lung injury induced by endotoxin. Clinical and Experimental Pharmacology and Physiology, vol. 33, no. 1–2, pp. 33–40. PMID: 16445696. DOI: 10.1111/j.1440-1681.2006.04320.x (In English)

Kazerani, H. R., Furman, B. L. (2006) Comparison of urethane/chloralose and pentobarbitone anaesthesia for examining effects of bacterial lipopolysaccharide in mice. Fundamental & Clinical Pharmacology, vol. 20, no. 4, pp. 379–384. PMID: 16867022. DOI: 10.1111/j.1472-8206.2006.00413.x (In English)

Kim, Y. K., Amidfar, M., Won, E. (2019) A review on inflammatory cytokine-induced alterations of the brain as potential neural biomarkers in post-traumatic stress disorder. Progress in Neuro-Psychopharmacology & Biologycal Psychiatry, vol. 91, pp. 103–112. PMID: 29932946. DOI: 10.1016/j.pnpbp.2018.06.008 (In English)

Mathiak, G., Grass, G., Herzmann, T. et al. (2000) Caspase-1-inhibitor ac-YVAD-cmk reduces LPS-lethality in rats without affecting haematology or cytokine responses. British Journal of Pharmacology, vol. 131, no. 3, pp. 383–386. PMID: 11015286. DOI: 10.1038/sj.bjp.0703629 (In English)

Muller, N. (2017) Immunological aspects of the treatment of depression and schizophrenia. Dialogues in Clinical Neuroscience, vol. 19, no. 1, pp. 55–63. PMID: 28566947. (In English)

Probert, L. (2015) TNF and its receptors in the CNS: The essential, the desirable and the deleterious effects. Neuroscience, vol. 302, pp. 2–22. PMID: 26117714. DOI: 10.1016/j.neuroscience.2015.06.038 (In English)

Roelfsema, V., Thomas, G. B., Lin, H. et al. (2001) The metabolic effects of endotoxin are differentially affected by the pattern of GH administration in the rat. Journal of Endocrinology, vol. 171, no. 1, pp. 173–181. PMID: 11572801. DOI: 10.1677/joe.0.1710173 (In English)

Rudiger, A., Stotz, M., Singer, M. (2008) Cellular processes in sepsis. Swiss Medical Weekly, vol. 138, no. 43–44, pp. 629–634. PMID: 19005868. (In English)

Schlapfer, M., Piegeler, T., Dull, R. O. et al. (2015) Propofol increases morbidity and mortality in a rat model of sepsis. Critical Care, vol. 19, article 45. PMID: 25887642. DOI: 10.1186/s13054-015-0751-x (In English)

Short, A., Wong, A. K., Finch, A. M. et al. (1999) Effects of a new C5a receptor antagonist on C5a- and endotoxininduced neutropenia in the rat. British Journal of Pharmacology, vol. 126, no. 3, pp. 551–554. PMID: 10188960. DOI: 10.1038/sj.bjp.0702338 (In English)

Stahl, O, Loffler, B., Haier, J. et al. (2013) Mimicry of human sepsis in a rat model — prospects and limitation. Journal of Surgical Research, vol. 179, no. 1, pp. e167–e175. PMID: 22482762. DOI: 10.1016/j.jss.2012.01.042 (In English)

Steven, S., Dib. M., Roohani, S. et al. (2017) Time response of oxidative/nitrosative stress and inflammation in LPS-induced endotoxemia — a comparative study of mice and rats. International Journal of Molecular Sciences, vol. 18, no. 10, article 2176. PMID: 29057830. DOI: 10.3390/ijms18102176 (In English)

Wagner, J. G. Roth, R. A. (1999) Neutrophil migration during endotoxemia. Journal of Leukocyte Biology, vol. 66, no. 1, pp. 10–24. PMID: 10410985. DOI: 10.1002/jlb.66.1.10 (In English)

Wong, K. A., Rodriguez, A. (2008) Plasmodium infection and endotoxic shock induce the expansion of regulatory dendritic cells. The Journal of Immunology, vol. 180, no. 2, pp. 716–726. PMID: 18178809. DOI: 10.4049/jimmunol.180.2.716 (In English)

Zimmerman, J. J., Ringer, T. V. (1992) Inflammatory host responses in sepsis. Progress in Pediatric Critical Care, vol. 8, no. 1, pp. 163–189. DOI: 10.1016/S0749-0704(18)30273-2 (In English)

REFERENCES

Altenburg, S. P., Martins, M. A., Silva, A. R. et al. (1997) LPS-induced blood neutrophilia is inhibited by alpha 1-adrenoceptor antagonists: A role for catecholamines. The Journal of Leukocyte Biology, vol. 61, no. 6, pp. 689–694. PMID: 9201259. DOI: 10.1002/jlb.61.6.689 (In English)

Beck-Schimmer, B., Baumann, L., Restin, T. et al. (2017) Sevoflurane attenuates systemic inflammation compared with propofol, but does not modulate neuro-inflammation: A laboratory rat study. European Journal of Anaesthesiology, vol. 34, no. 11, pp. 764–775. PMID: 28759530. DOI: 10.1097/EJA.0000000000000668 (In English)

Benveniste, E. N. (1998) Cytokine actions in the central nervous system. Cytokine & Growth Factors Reviews, vol. 9, no. 3–4, pp. 259–275. PMID: 9918124. DOI: 10.1016/S1359-6101(98)00015-X (In English)

Black, P. H. (1994) Immune system-central nervous system interactions: Effect and immunomodulatory consequences of immune system mediators on the brain. Antimicrobial Agents and Chemotherapy, vol. 38, no. 1, pp. 7–12. PMID: 8141583. DOI: 10.1128/AAC.38.1.7 (In English)

Bone, R. C. (1996) Toward a theory regarding the pathogenesis of the systemic inflammatory response syndrome: What we do and do not know about cytokine regulation. Critical Care Medicine, vol. 24, no. 1, pp. 163–172. PMID: 8565523. DOI: 10.1097/00003246-199601000-00026 (In English)

Bone, R. C., Balk, R. A., Cerra, F. B. et al. (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest, vol. 101, no. 6, pp. 1644–1655. PMID: 1303622. DOI: 10.1378/chest.101.6.1644 (In English)

Cao, C., Matsumura, K., Yamagata, K., Watanabe, Y. (1997) Involvement of cyclooxygenase-2 in LPS-induced fever and regulation of its mRNA by LPS in the rat brain. American Journal of Physiology, vol. 272, no. 6, pt. 2, pp. R1712–R1725. PMID: 9227582. DOI: 10.1152/ajpregu.1997.272.6.R1712 (In English)

Castro-Faria-Neto, H. C., Penido, C. M., Larangeira, A. P. et al. (1997) A role for limphocytes and cytokines on the eosinophil migration induced by LPS. Memórias do Instituto Oswaldo Cruz, vol. 92, suppl. II, pp. 197–200. PMID: 9698933. DOI: 10.1590/s0074-02761997000800026 (In English)

Chereshnev, V. A., Gusev, E. Yu. (2002) Sistemnoe vospalenie kak immunopatobiologicheskij fenomen [Systemic inflammation as an immunopathobiological phenomenon]. Tsitokiny i vospalenie — Cytokines and inflammation, vol. 1, no. 2, p. 17. (In Russian)

Chereshnev, V. A., Shilov, M. I., Chereshneva M. V., et al. (2011) Eksperimental’nye modeli v patologii [Experimental models in pathology]. Perm: Perm State University Publ., 267 p. (In Russian)

Feuerstein, G., Hallenbeck, J. M., Vanatta, B. et al (1990) Effect of gram-negative endotoxin on levels of serum corticosterone, TNF alpha, circulating blood cells, and the survival of rats. Circulatory Shock, vol. 30, no. 3, pp. 265–78. PMID: 2178800. (In English)

Galkin, A. A., Demidova, V. S. (2015) Nejtrofily i sindrom sistemnogo vospalitel’nogo otveta [Neutrophils and systemic inflammatory response syndrome]. Rany i ranevye infekcii. Zhurnal imeni prof. B. M. Kostyuchenka — Wounds and Wound Infections. The Prof. B. M. Kostyuchenok Journal, vol. 2, no. 2, pp. 25–31. (In Russian)

Garami, A., Steiner, A. A., Romanovsky, A. A. (2018) Fever and hypothermia in systemic inflammation. Handbook of Clinical Neurology, vol. 157, pp. 565–597. PMID: 30459026. DOI: 10.1016/B978-0-444-64074-1.00034-3 (In English)

Gel’fand, B. R., Saltanov, A. I. (ed.) (2009) Intensivnaya terapiya: natsional’noe rukovodstvo [Intensive care: A national manual]: In 2 vols. Vol. 1. Moscow: GEOTAR-Media Publ., 955 p. (In Russian)

Herzum, I., Renz, H. (2008) Inflammatory markers in SIRS, sepsis and septic shock. Current Medicinal Chemistry, vol. 15, no. 6, pp. 581–587. PMID: 18336272. DOI: 10.2174/092986708783769704 (In English)

Kao, S. J., Wang, D., Lin, H. I., Chen, H. I. (2006) N-acetylcysteine abrogates acute lung injury induced by endotoxin. Clinical and Experimental Pharmacology and Physiology, vol. 33, no. 1–2, pp. 33–40. PMID: 16445696. DOI: 10.1111/j.1440-1681.2006.04320.x (In English)

Kazerani, H. R., Furman, B. L. (2006) Comparison of urethane/chloralose and pentobarbitone anaesthesia for examining effects of bacterial lipopolysaccharide in mice. Fundamental & Clinical Pharmacology, vol. 20, no. 4, pp. 379–384. PMID: 16867022. DOI: 10.1111/j.1472-8206.2006.00413.x (In English)

Kim, Y. K., Amidfar, M., Won, E. (2019) A review on inflammatory cytokine-induced alterations of the brain as potential neural biomarkers in post-traumatic stress disorder. Progress in Neuro-Psychopharmacology & Biologycal Psychiatry, vol. 91, pp. 103–112. PMID: 29932946. DOI: 10.1016/j.pnpbp.2018.06.008 (In English)

Mathiak, G., Grass, G., Herzmann, T. et al. (2000) Caspase-1-inhibitor ac-YVAD-cmk reduces LPS-lethality in rats without affecting haematology or cytokine responses. British Journal of Pharmacology, vol. 131, no. 3, pp. 383–386. PMID: 11015286. DOI: 10.1038/sj.bjp.0703629 (In English)

Mezhirova, N. M., Danilova V. V., Ovcharenko, S. S. (2011) Patofiziologicheskie i diagnosticheskie aspekty sindroma sistemnogo vospalitel’nogo otveta [Pathophysiological and diagnostic aspects of the systemic inflammatory response syndrome]. Meditsina neotlozhnykh sostoyanij — Emergency Medicine, no. 1–2, pp. 34–40. (In Russian)

Muller, N. (2017) Immunological aspects of the treatment of depression and schizophrenia. Dialogues in Clinical Neuroscience, vol. 19, no. 1, pp. 55–63. PMID: 28566947. (In English)

Probert, L. (2015) TNF and its receptors in the CNS: The essential, the desirable and the deleterious effects. Neuroscience, vol. 302, pp. 2–22. PMID: 26117714. DOI: 10.1016/j.neuroscience.2015.06.038 (In English)

Roelfsema, V., Thomas, G. B., Lin, H. et al. (2001) The metabolic effects of endotoxin are differentially affected by the pattern of GH administration in the rat. Journal of Endocrinology, vol. 171, no. 1, pp. 173–181. PMID: 11572801. DOI: 10.1677/joe.0.1710173 (In English)

Rudiger, A., Stotz, M., Singer, M. (2008) Cellular processes in sepsis. Swiss Medical Weekly, vol. 138, no. 43–44, pp. 629–634. PMID: 19005868. (In English)

Schlapfer, M., Piegeler, T., Dull, R. O. et al. (2015) Propofol increases morbidity and mortality in a rat model of sepsis. Critical Care, vol. 19, article 45. PMID: 25887642. DOI: 10.1186/s13054-015-0751-x (In English)

Short, A., Wong, A. K., Finch, A. M. et al. (1999) Effects of a new C5a receptor antagonist on C5a- and endotoxininduced neutropenia in the rat. British Journal of Pharmacology, vol. 126, no. 3, pp. 551–554. PMID: 10188960. DOI: 10.1038/sj.bjp.0702338 (In English)

Simbirtsev, A. S., Totolyan, A. A. (2015) Tsitokiny v laboratornoj diagnostike [Cytokines in laboratory diagnostics]. Infektsionnye bolezni — Infectious Diseases, no. 2, pp. 82–98. (In Russian)

Stahl, O, Loffler, B., Haier, J. et al. (2013) Mimicry of human sepsis in a rat model — prospects and limitation. Journal of Surgical Research, vol. 179, no. 1, pp. e167–e175. PMID: 22482762. DOI: 10.1016/j.jss.2012.01.042 (In English)

Steven, S., Dib. M., Roohani, S. et al. (2017) Time response of oxidative/nitrosative stress and inflammation in LPS-induced endotoxemia — a comparative study of mice and rats. International Journal of Molecular Sciences, vol. 18, no. 10, article 2176. PMID: 29057830. DOI: 10.3390/ijms18102176 (In English)

Tumanova, T. S., Aleksandrov, V. G. (2016) Vliyanie bakterial’nogo lipopolisakharida na reflektornye mekhanizmy kardiorespiratornoj sistemy anestezirovannoj krysy [The effect of bacterial lipopolysaccharide on the reflex mechanisms of the cardiorespiratory system of anesthetized rat]. In: A. I. Grigor’ev, Yu. V. Natochin, R. I. Sepiashvili et al. (eds.). Nauchnye trudy V S’ezda fiziologov SNG, V S’ezda biokhimikov Rossii, Konferentsii ADFLIM. [Academic Works of V Congress of CIS physiologists, V Congress of Biochemists of Russia, ADFLIM conference]. Sochi: s. n., p. 158. (Acta Naturae. Special issue, vol. 1). (In Russian)

Wagner, J. G. Roth, R. A. (1999) Neutrophil migration during endotoxemia. Journal of Leukocyte Biology, vol. 66, no. 1, pp. 10–24. PMID: 10410985. DOI: 10.1002/jlb.66.1.10 (In English).

Wong, K. A., Rodriguez, A. (2008) Plasmodium infection and endotoxic shock induce the expansion of regulatory dendritic cells. The Journal of Immunology, vol. 180, no. 2, pp. 716–726. PMID: 18178809. DOI: 10.4049/jimmunol.180.2.716 (In English)

Zimmerman, J. J., Ringer, T. V. (1992) Inflammatory host responses in sepsis. Progress in Pediatric Critical Care, vol. 8, no. 1, pp. 163–189. DOI: 10.1016/S0749-0704(18)30273-2 (In English)

Опубликован

02.03.2020

Выпуск

Раздел

Экспериментальные статьи