Нейропротективный эффект докозагексаеновой и эйкозопентаеновой полиненасыщенных жирных кислот и перинатальная защита мозга плода (клинико-фармакологическая лекция)
Нейропротективный эффект докозагексаеновой и эйкозопентаеновой полиненасыщенных жирных кислот и перинатальная защита мозга плода (клинико-фармакологическая лекция)
Нейропротективный эффект докозагексаеновой и эйкозопентаеновой полиненасыщенных жирных кислот и перинатальная защита мозга плода (клинико-фармакологическая лекция)
Докозагексаеновая кислота (ДГК) является представителем полиненасыщенных жирных кислот (ПНЖК) с широким спектором физиологической активности: противовоспалительным, антиаритмическим, противотромботическим действием и наиболее выраженным нейропротективным и офтальмопротективным эффектом. Большое количество биохимических, экспериментальных и клинических исследований свидетельствует об успешном применении стандартизированных форм омега-3 ПНЖК в кардиологии, терапии и профилактике сахарного диабета, неврологических заболеваний, онкологической патологии и др. В настоящей работе рассмотрены перспективы клинического применения докозагексаеновой омега-3 ПНЖК в защите мозга плода. Приведены результаты фундаментальных исследований и доказательной медицины, указывающие на ключевую роль жирных кислот в виде ДГК в нейропротекции, когнитивном развитии ребенка и профилактике синдрома гиперактивности с дефицитом внимания.
Docosahexaenoic acid (DHA) is representing Omega-3 polyunsaturated fatty acids (PUFAs) with a wide range of physiological effects which include anti-inflammatory, antiarrhythmic, antiplatelet activities and most prominent effects of ophthalmo- and neuroprotection. A huge base of biochemical, experimental and clinical studies have demonstrated the successful use of the standardized forms of omega-3 PUFAs in therapy and prevention of cardiovascular diseases, diabetes, neurological diseases, cancer, etc. In this paper, we consider the prospects for clinical use of standardized forms of omega-3 PUFAs as DHA in the neuroprotection of the fetal brain. The results of basic research and evidence-based medicine demonstrated the essential role of DHA as one of omega-3 PUFAs in neuroprotection, cognitive development and prevention of hyperactivity in infants and children.
1. Торшин И.Ю., Громова О.А., Егорова Е.Ю. Систематический анализ молекулярных механизмов воздействия омега-3 полиненасыщенных жирных кислот на аритмию. Кардиология, 2011; 5: 37–49.
2. Громова О.А., Торшин И.Ю., Сухих Г.Т и др. Роли различных форм омега-3 ПНЖК в акушерстве и неонатологии. Публикация в рамках реализации Национального проекта «Здоровье». М., 2009.
3. Торшин И.Ю., Гусев Е.И., Громова О.А., Рудаков К.В. Систематический анализ мирового опыта изучения неврологических эффектов омега-3 ПНЖК. Журн. неврол. и психиат. им. С.С.Корсакова, 2011; 12.
4. Marchioli R, Barzi F, Bomba E et al. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione. Circulation 2002; 105 (16): 1897–903.
5. GISSI-Prevenzione Study Group. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet 1999; 354 (9177): 447–55.
6. Marik PE, Varon J. Omega-3 dietary supplements and the risk of cardiovascular events: a systematic review. Clin Cardiol 2009; 32 (7): 365–72.
7. Tate J, Bushnell C. Pregnancy and stroke risk in women. Womens Health 2011; 7 (3): 363–74.
8. Hibbeln JR. Seafood consumption, the DHA content of mothers' milk and prevalence rates of postpartum depression: a cross-national, ecological analysis. J Affect Disord 2002; 69 (1–3): 15–29.
9. Muggli R. LCFUPA and brain health. DSM Nutritional products 2007; p. 4.
10. Bakker EC et al. Long-chain polyunsaturated fatty acids at birth and motor function at 7 years of age, in Long-chain polyunsaturated fatty acids and child development. Universitaire Pers Maastricht 2002; p. 47–102.
11. Ryan AS, Nelson EB. Assessing the effect of docosahexaenoic acid on cognitive functions in healthy, preschool children: a randomized, placebo-controlled, double-blind study. Clin Pediatr 2008; 47 (4): 355–62.
12. Ikemoto A et al. Reversibility of n-3 fatty acid deficiency-induced alterations of learning behavior in the rat: level of n-6 fatty acids as another critical factor. J Lipid Res 2001; 42 (10): 1655–63.
13.Wauben IP et al. Dietary trans fatty acids combined with a marginal essential fatty acid status during the pre- and postnatal periods do not affect growth or brain fatty acids but may alter behavioral development in B6D2F(2) mice. J Nutr 2001; 131 (5): 1568–73.
14. Tilley SL, Coffman TM, Koller BH. Mixed messages: modulation of inflammation and immune responses by prostaglandins and thromboxanes. J Clin Invest 2001; 108 (1): 15–23.
15. Wada M, DeLong CJ, Hong YH et al. Enzymes and receptors of prostaglandin pathways with arachidonic acid-derived versus eicosapentaenoic acid-derived substrates and products. J Biol Chem 2007; 282 (31): 22254–66.
16. Serhan CN. Novel eicosanoid and docosanoid mediators: resolvins, docosatrienes and neuroprotectins. Curr Opin Clin Nutr Metab Care 2005; 8 (2): 115–21.
17.Oh SF, Pillai PS, Recchiuti A et al. Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammation. J Clin Invest 2011; 121 (2): 569–81 doi.
18. Xue H, Wan M, Song D et al. Eicosapentaenoic acid and docosahexaenoic acid modulate mitogen-activated protein kinase activity in endothelium. Epub 2006 Apr. Vascul Pharmacol 2006; 44 (6): 434–9.
19. Громова О.А., Торшин И.Ю. Резолвины и нейропротектины: систематический анализ нейропротективных производных омега-3 ПНЖК. Журн. неврол. и психиат. им С.С.Корсакова, 2011; 11.
20. Chiang N, Arita M, Serhan CN. Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature 2007; 447 (7146): 869–74.
21. Marcheselli VL, Bazan NG. Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J Biol Chem 2003; 278 (44): 43807.
22. Antony R, Lukiw WJ, Bazan NG. Neuroprotectin D1 induces dephosphorylation of Bcl-xL in a PP2A-dependent manner during oxidative stress and promotes retinal pigment epithelial cell survival. J Biol Chem 2010; 285 (24): 18301–8.
23. Brink C, Dahlen SE, Drazen J et al. International Union of Pharmacology XXXVII. Nomenclature for leukotriene and lipoxin receptors. Pharmacol Rev 2003; 55 (1): 195–227.
24. Uddin M, Levy BD. Resolvins: natural agonists for resolution of pulmonary inflammation. Prog Lipid Res 2011; 50 (1): 75–88.
25. Cheatham CL, Nerhammer AS, Asserhøj M et al. Fish oil supplementation during lactation: effects on cognition and behavior at 7 years of age. Lipids 2011; 46 (7): 637–45.
26. Ohira T, Arita M, Omori K et al. Resolvin E1 receptor activation signals phosphorylation and phagocytosis. J Biol Chem 2010; 285 (5): 3451–61.
27. Duffield JS, Hong S, Vaidya VS et al. Resolvin D series and protectin D1 mitigate acute kidney injury. J Immunol 2006; 177 (9): 5902–11.
28. Нормы СанПиН 2.3.2. 1290.03 «Гигиенические требования к организации производства и обороту биологически активных добавок к пище».
29. Персианинов Л.С. Антенатальная охрана плода. М.: Медицина, 1964.
30. Гармашева Н.Л. Плацентарное кровообращение. Л., 1967.
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1. Торшин И.Ю., Громова О.А., Егорова Е.Ю. Систематический анализ молекулярных механизмов воздействия омега-3 полиненасыщенных жирных кислот на аритмию. Кардиология, 2011; 5: 37–49.
2. Громова О.А., Торшин И.Ю., Сухих Г.Т и др. Роли различных форм омега-3 ПНЖК в акушерстве и неонатологии. Публикация в рамках реализации Национального проекта «Здоровье». М., 2009.
3. Торшин И.Ю., Гусев Е.И., Громова О.А., Рудаков К.В. Систематический анализ мирового опыта изучения неврологических эффектов омега-3 ПНЖК. Журн. неврол. и психиат. им. С.С.Корсакова, 2011; 12.
4. Marchioli R, Barzi F, Bomba E et al. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione. Circulation 2002; 105 (16): 1897–903.
5. GISSI-Prevenzione Study Group. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet 1999; 354 (9177): 447–55.
6. Marik PE, Varon J. Omega-3 dietary supplements and the risk of cardiovascular events: a systematic review. Clin Cardiol 2009; 32 (7): 365–72.
7. Tate J, Bushnell C. Pregnancy and stroke risk in women. Womens Health 2011; 7 (3): 363–74.
8. Hibbeln JR. Seafood consumption, the DHA content of mothers' milk and prevalence rates of postpartum depression: a cross-national, ecological analysis. J Affect Disord 2002; 69 (1–3): 15–29.
9. Muggli R. LCFUPA and brain health. DSM Nutritional products 2007; p. 4.
10. Bakker EC et al. Long-chain polyunsaturated fatty acids at birth and motor function at 7 years of age, in Long-chain polyunsaturated fatty acids and child development. Universitaire Pers Maastricht 2002; p. 47–102.
11. Ryan AS, Nelson EB. Assessing the effect of docosahexaenoic acid on cognitive functions in healthy, preschool children: a randomized, placebo-controlled, double-blind study. Clin Pediatr 2008; 47 (4): 355–62.
12. Ikemoto A et al. Reversibility of n-3 fatty acid deficiency-induced alterations of learning behavior in the rat: level of n-6 fatty acids as another critical factor. J Lipid Res 2001; 42 (10): 1655–63.
13.Wauben IP et al. Dietary trans fatty acids combined with a marginal essential fatty acid status during the pre- and postnatal periods do not affect growth or brain fatty acids but may alter behavioral development in B6D2F(2) mice. J Nutr 2001; 131 (5): 1568–73.
14. Tilley SL, Coffman TM, Koller BH. Mixed messages: modulation of inflammation and immune responses by prostaglandins and thromboxanes. J Clin Invest 2001; 108 (1): 15–23.
15. Wada M, DeLong CJ, Hong YH et al. Enzymes and receptors of prostaglandin pathways with arachidonic acid-derived versus eicosapentaenoic acid-derived substrates and products. J Biol Chem 2007; 282 (31): 22254–66.
16. Serhan CN. Novel eicosanoid and docosanoid mediators: resolvins, docosatrienes and neuroprotectins. Curr Opin Clin Nutr Metab Care 2005; 8 (2): 115–21.
17.Oh SF, Pillai PS, Recchiuti A et al. Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammation. J Clin Invest 2011; 121 (2): 569–81 doi.
18. Xue H, Wan M, Song D et al. Eicosapentaenoic acid and docosahexaenoic acid modulate mitogen-activated protein kinase activity in endothelium. Epub 2006 Apr. Vascul Pharmacol 2006; 44 (6): 434–9.
19. Громова О.А., Торшин И.Ю. Резолвины и нейропротектины: систематический анализ нейропротективных производных омега-3 ПНЖК. Журн. неврол. и психиат. им С.С.Корсакова, 2011; 11.
20. Chiang N, Arita M, Serhan CN. Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature 2007; 447 (7146): 869–74.
21. Marcheselli VL, Bazan NG. Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J Biol Chem 2003; 278 (44): 43807.
22. Antony R, Lukiw WJ, Bazan NG. Neuroprotectin D1 induces dephosphorylation of Bcl-xL in a PP2A-dependent manner during oxidative stress and promotes retinal pigment epithelial cell survival. J Biol Chem 2010; 285 (24): 18301–8.
23. Brink C, Dahlen SE, Drazen J et al. International Union of Pharmacology XXXVII. Nomenclature for leukotriene and lipoxin receptors. Pharmacol Rev 2003; 55 (1): 195–227.
24. Uddin M, Levy BD. Resolvins: natural agonists for resolution of pulmonary inflammation. Prog Lipid Res 2011; 50 (1): 75–88.
25. Cheatham CL, Nerhammer AS, Asserhøj M et al. Fish oil supplementation during lactation: effects on cognition and behavior at 7 years of age. Lipids 2011; 46 (7): 637–45.
26. Ohira T, Arita M, Omori K et al. Resolvin E1 receptor activation signals phosphorylation and phagocytosis. J Biol Chem 2010; 285 (5): 3451–61.
27. Duffield JS, Hong S, Vaidya VS et al. Resolvin D series and protectin D1 mitigate acute kidney injury. J Immunol 2006; 177 (9): 5902–11.
28. Нормы СанПиН 2.3.2. 1290.03 «Гигиенические требования к организации производства и обороту биологически активных добавок к пище».
29. Персианинов Л.С. Антенатальная охрана плода. М.: Медицина, 1964.
30. Гармашева Н.Л. Плацентарное кровообращение. Л., 1967.
Авторы
О.А.Громова, Н.В.Керимкулова
РСЦ Института микроэлементов ЮНЕСКО, Москва;
ГБОУ ВПО Ивановская государственная медицинская академия Минздравсоцразвития РФ