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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">pulmo</journal-id><journal-title-group><journal-title xml:lang="ru">Пульмонология</journal-title><trans-title-group xml:lang="en"><trans-title>PULMONOLOGIYA</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">0869-0189</issn><issn pub-type="epub">2541-9617</issn><publisher><publisher-name>Scientific and Practical Journal “PULMONOLOGIYA” LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.18093/0869-0189-2015-25-2-151-156</article-id><article-id custom-type="elpub" pub-id-type="custom">pulmo-547</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL STUDIES</subject></subj-group></article-categories><title-group><article-title>Экспрессия генов ADRB2 и CHRM3 в лейкоцитах крови у больных с обострением хронической обструктивной болезни легких</article-title><trans-title-group xml:lang="en"><trans-title>ADRB2 and CHRM3 gene expression in blood leukocytes of patients with acute exacerbation of chronic obstructive pulmonary disease</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Чухловин</surname><given-names>А. Б.</given-names></name><name name-style="western" xml:lang="en"><surname>Chukhlovin</surname><given-names>A. B.</given-names></name></name-alternatives><bio xml:lang="ru"><p>д. м. н., профессор, зам. директора НИИ детской онкологии, гематологии и трансплантологии им. Р.М.Горбачевой ГБОУ ВПО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П.Павлова» Минздрава России; тел.: (812) 233-48-51;</p></bio><bio xml:lang="en"><p>MD, Professor, Deputy Director, R.M.Gorbacheva Scientific and Research Institute of Pediatric Oncology, Haematology and Transplantology, State Institution “Academician I.P.Pavlov First Saint-Petersburg State Medical University”, Healthcare Ministry of Russia; tel.: (812) 233-48-51;</p></bio><email xlink:type="simple">alexei.chukh@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кузубова</surname><given-names>Н. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kuzubova</surname><given-names>N. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>д. м. н., зам. директора НИИ пульмонологии ГБОУ ВПО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П.Павлова» Минздрава России; тел.: (812) 234-17-69; </p></bio><bio xml:lang="en"><p>MD, Professor, Deputy Director, Scientific and Research Pulmonology Institute, State Institution “Academician I.P.Pavlov First Saint-Petersburg State Medical University”, Healthcare Ministry of Russia; tel.: (812) 234-17-69;</p></bio><email xlink:type="simple">kuzubova@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Елшин</surname><given-names>Н. Д.</given-names></name><name name-style="western" xml:lang="en"><surname>Elshin</surname><given-names>N. D.</given-names></name></name-alternatives><bio xml:lang="ru"><p>аспирант кафедры клинической лабораторной диагностики ГБОУ ВПО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П.Павлова» Минздрава России; тел. / факс: (812) 233-97-26;</p></bio><bio xml:lang="en"><p>PhD student, Department of Clinical and Laboratory Diagnostics, State Institution “Academician I.P.Pavlov First Saint-Petersburg State Medical University”, Healthcare Ministry of Russia; tel.: / fax: (812) 233-97-26;</p></bio><email xlink:type="simple">nikita.yolshin@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Титова</surname><given-names>О. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Titova</surname><given-names>O. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>д. м. н., директор НИИ пульмонологии ГБОУ ВПО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П.Павлова» Минздрава России; тел.: (812) 499-68-40;</p></bio><bio xml:lang="en"><p>MD, Director, Scientific and Research Pulmonology Institute, State Institution “Academician I.P.Pavlov First Saint-Petersburg State Medical University”, Healthcare Ministry of Russia; tel.: (812) 499-68-40</p></bio><email xlink:type="simple">pulmorg@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ГБОУ ВПО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П.Павлова» Минздрава России: 197089, Россия, Санкт-Петербург, ул. Л.Толстого, 6 / 8</institution><country>Россия</country></aff><aff xml:lang="en"><institution>State Institution “Academician I.P.Pavlov First Saint-Petersburg State Medical University”, Healthcare Ministry of Russia: 6 / 8, L'va Tolstogo ul., Saint-Petersburg, 197089, Russia</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2015</year></pub-date><pub-date pub-type="epub"><day>24</day><month>06</month><year>2015</year></pub-date><volume>25</volume><issue>2</issue><fpage>151</fpage><lpage>156</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Чухловин А.Б., Кузубова Н.А., Елшин Н.Д., Титова О.Н., 2015</copyright-statement><copyright-year>2015</copyright-year><copyright-holder xml:lang="ru">Чухловин А.Б., Кузубова Н.А., Елшин Н.Д., Титова О.Н.</copyright-holder><copyright-holder xml:lang="en">Chukhlovin A.B., Kuzubova N.A., Elshin N.D., Titova O.N.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://journal.pulmonology.ru/pulm/article/view/547">https://journal.pulmonology.ru/pulm/article/view/547</self-uri><abstract><p>Целью пилотного исследования явилась оценка уровней активности генов ADRB2 и CHRM3 в лейкоцитах крови у пациентов (n = 29) с обострениями хронической обструктивной болезни легких (II–III стадия, группа D по GOLD) на фоне 2-недельного комплексного лечения с применением антибактериальной терапии, тиотропия бромида, Формотерола и ингаляций глюкокортикостероидов (ГКС). До и после лечения определялось содержание мРНК генов адрено- и холинорецепторов (ADRB2 и CHRM3) в лейкоцитах крови больных. Средние значения экспрессии изученных генов достоверно не различались до и после лечения. Выявлены достоверные корреляции между изменениями экспрессии генов ADRB2 и CHRM3, динамикой объема форсированного выдоха за 1-ю секунду и уровнями С-реактивного белка в крови после купирования обострения. По результатам работы подтверждена возможность модуляции адренорецепторов под влиянием #b-агонистов и ингаляций ГКС, а также ингибирования экспрессии М-холинорецепторов при сочетанном применении ГКС и М-холинолитиков.</p></abstract><trans-abstract xml:lang="en"><p>This pilot study was aimed at evaluation of ADRB2 and CHRM3 gene expression in COPD. Methods. We evaluated ADRB2 and CHRM3 gene expression in blood leukocytes from 29 patients with acute exacerbation of COPD (GOLD stage II to III, Group D) before and after 2-week combined therapy including antimicrobials, tiotropium bromide, formoterol and an inhaled steroid. ADRB2- and CHRM3-specific mRNA content was determined in leukocytes using real-time PCR. Results. Mean gene expression levels did not differ before and after treatment. However, we found a significant correlation between changes in ADRB2 and CHRM3 gene expression, change in FEV1 and post-treatment C-reactive protein level.</p><p>Conclusion. The results confirm a possibility to affect adrenoceptors using beta agonists and inhaled steroids and to inhibit M-cholinoreceptor expression with M3-cholinolytics and inhaled steroids.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>хроническая обструктивная болезнь легких</kwd><kwd>комплексная терапия</kwd><kwd>лейкоциты</kwd><kwd>CHRM3</kwd><kwd>ADRB2</kwd><kwd>экспрессия генов</kwd></kwd-group><kwd-group xml:lang="en"><kwd>chronic obstructive lung disease</kwd><kwd>combined therapy</kwd><kwd>leukocytes</kwd><kwd>CHRM3</kwd><kwd>ADRB2</kwd><kwd>gene expression</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Chuchalin A.G., Avdeev S.N., Aysanov Z.R. et al. Federal guidelines on diagnosis and management of chronic obstructive pulmonary disease. Moscow: Rossiyskoe respiratornoe obshchestvo; 2013 (in Russian).</mixed-citation><mixed-citation xml:lang="en">Chuchalin A.G., Avdeev S.N., Aysanov Z.R. et al. Federal guidelines on diagnosis and management of chronic obstructive pulmonary disease. Moscow: Rossiyskoe respiratornoe obshchestvo; 2013 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Dale Ph.R., Cernecka H., Schmidt M. et al. The pharmacological rationale for combining muscarinic receptor antagonists and β-adrenoceptor agonists in the treatment of airway and bladder disease. Curr. Opin. Pharmacol. 2014; 16: 31–42.</mixed-citation><mixed-citation xml:lang="en">Dale Ph.R., Cernecka H., Schmidt M. et al. The pharmacological rationale for combining muscarinic receptor antagonists and β-adrenoceptor agonists in the treatment of airway and bladder disease. Curr. Opin. Pharmacol. 2014; 16: 31–42.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Ogorodova L.M., Chernyak B.A., Kozina O.V. et al. Molecular aspects of different phenotypes of chronic obstructive pulmonary disease. Pul'monologiya. 2013; 1: 5–11 (in Russian).</mixed-citation><mixed-citation xml:lang="en">Ogorodova L.M., Chernyak B.A., Kozina O.V. et al. Molecular aspects of different phenotypes of chronic obstructive pulmonary disease. Pul'monologiya. 2013; 1: 5–11 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Kin N.W., Sanders V.M. It takes nerve to tell T and B cells what to do. J. Leukoc. Biol. 2006; 79 (6): 1093–1104.</mixed-citation><mixed-citation xml:lang="en">Kin N.W., Sanders V.M. It takes nerve to tell T and B cells what to do. J. Leukoc. Biol. 2006; 79 (6): 1093–1104.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Yu X.Y., Lin S.G., Wang X.M. et al. Evidence for coexistence of three #b-adrenoceptor subtypes in human peripheral lymphocytes. Clin. Pharmacol. Ther. 2007; 81 (5): 654–658.</mixed-citation><mixed-citation xml:lang="en">Yu X.Y., Lin S.G., Wang X.M. et al. Evidence for coexistence of three #b-adrenoceptor subtypes in human peripheral lymphocytes. Clin. Pharmacol. Ther. 2007; 81 (5): 654–658.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Fujii T., Takada-Takatori Y., Kawashima K. Basic and clinical aspects of non-neuronal acetylcholine: expression of an independent, non-neuronal cholinergic system in lymphocytes and its clinical significance in immunotherapy. J. Pharmacol. Sci. 2008; 106 (2): 186–192.</mixed-citation><mixed-citation xml:lang="en">Fujii T., Takada-Takatori Y., Kawashima K. Basic and clinical aspects of non-neuronal acetylcholine: expression of an independent, non-neuronal cholinergic system in lymphocytes and its clinical significance in immunotherapy. J. Pharmacol. Sci. 2008; 106 (2): 186–192.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Klement R.F., Lavrushin A.A., Ter-Pogosyan P.A. User guide on formulas and tables of reference values for general spirometric parameters. Leningrad; 1986 (in Russian).</mixed-citation><mixed-citation xml:lang="en">Klement R.F., Lavrushin A.A., Ter-Pogosyan P.A. User guide on formulas and tables of reference values for general spirometric parameters. Leningrad; 1986 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Moniotte S., Vaerman J.L., Kockx M.M. et al. Real-time RT-PCR for the detection of beta-adrenoceptor messenger RNAs in small human endomyocardial biopsies. J. Mol. Cell. Cardiol. 2001; 33 (12): 2121–2133.</mixed-citation><mixed-citation xml:lang="en">Moniotte S., Vaerman J.L., Kockx M.M. et al. Real-time RT-PCR for the detection of beta-adrenoceptor messenger RNAs in small human endomyocardial biopsies. J. Mol. Cell. Cardiol. 2001; 33 (12): 2121–2133.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Patel N., Itakura T., Gonzalez J.M. Jr et al. GPR158, an orphan member of G protein-coupled receptor family C: glucocorticoid-stimulated expression and novel nuclear role. PLoS One. 2013; 8 (2): e57843. DOI: 10.1371/journal.pone.0057843.</mixed-citation><mixed-citation xml:lang="en">Patel N., Itakura T., Gonzalez J.M. Jr et al. GPR158, an orphan member of G protein-coupled receptor family C: glucocorticoid-stimulated expression and novel nuclear role. PLoS One. 2013; 8 (2): e57843. DOI: 10.1371/journal.pone.0057843.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Braden G.L., Germain M.J., Mulhern J.G. et al. Hemodynamic, cardiac, and electrolyte effects of low-dose aerosolized terbutaline sulfate in asthmatic patients. Chest. 1998; 114 (2): 380–387.</mixed-citation><mixed-citation xml:lang="en">Braden G.L., Germain M.J., Mulhern J.G. et al. Hemodynamic, cardiac, and electrolyte effects of low-dose aerosolized terbutaline sulfate in asthmatic patients. Chest. 1998; 114 (2): 380–387.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Bjermer L., Bengtsson Th., Jorup C. et al. Local and systemic effects of inhaled AZD9164 compared with tiotropium in patients with COPD. Respir. Med. 2013; 107 (1): 84–90.</mixed-citation><mixed-citation xml:lang="en">Bjermer L., Bengtsson Th., Jorup C. et al. Local and systemic effects of inhaled AZD9164 compared with tiotropium in patients with COPD. Respir. Med. 2013; 107 (1): 84–90.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Theron A.J., Steel H.C., Tintinger G.R. et al. Can the anti-inflammatory activities of #b2-agonists be harnessed in the clinical setting? Drug Des .Devel. Ther. 2013; 7: 1387–1398.</mixed-citation><mixed-citation xml:lang="en">Theron A.J., Steel H.C., Tintinger G.R. et al. Can the anti-inflammatory activities of #b2-agonists be harnessed in the clinical setting? Drug Des .Devel. Ther. 2013; 7: 1387–1398.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Black J.L., Oliver B.G.G., Roth M. Molecular mechanisms of combination therapy with inhaled corticosteroids and long-acting #b-agonists. Chest. 2009; 136 (4): 1095–1100.</mixed-citation><mixed-citation xml:lang="en">Black J.L., Oliver B.G.G., Roth M. Molecular mechanisms of combination therapy with inhaled corticosteroids and long-acting #b-agonists. Chest. 2009; 136 (4): 1095–1100.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Dalby Ch., Polanowski T., Larsson Th. et al. The bioavailability and airway clearance of the steroid component of budesonide / formoterol and salmeterol/fluticasone after inhaled administration in patients with COPD and healthy subjects: a randomized controlled trial. Respir. Res. 2009; 10: 104. DOI: 10.1186/1465-9921-10-104.</mixed-citation><mixed-citation xml:lang="en">Dalby Ch., Polanowski T., Larsson Th. et al. The bioavailability and airway clearance of the steroid component of budesonide / formoterol and salmeterol/fluticasone after inhaled administration in patients with COPD and healthy subjects: a randomized controlled trial. Respir. Res. 2009; 10: 104. DOI: 10.1186/1465-9921-10-104.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Rüdiger J.J., Gencay M., Yang J.Q. et al. Fast beneficial systemic anti-inflammatory effects of inhaled budesonide and formoterol on circulating lymphocytes in asthma. Respirology. 2013; 18 (5): 840–847.</mixed-citation><mixed-citation xml:lang="en">Rüdiger J.J., Gencay M., Yang J.Q. et al. Fast beneficial systemic anti-inflammatory effects of inhaled budesonide and formoterol on circulating lymphocytes in asthma. Respirology. 2013; 18 (5): 840–847.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Barnes P.J. Scientific rationale for inhaled combination therapy with long-acting #b2-agonists and corticosteroids. Eur. Respir. J. 2002; 19 (1): 182–191.</mixed-citation><mixed-citation xml:lang="en">Barnes P.J. Scientific rationale for inhaled combination therapy with long-acting #b2-agonists and corticosteroids. Eur. Respir. J. 2002; 19 (1): 182–191.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Oakley R.H., Cidlowski J.A. The biology of the glucocorticoid receptor: new signaling mechanisms in health and disease. J. Allergy Clin. Immunol. 2013; 132 (5): 1033–1044.</mixed-citation><mixed-citation xml:lang="en">Oakley R.H., Cidlowski J.A. The biology of the glucocorticoid receptor: new signaling mechanisms in health and disease. J. Allergy Clin. Immunol. 2013; 132 (5): 1033–1044.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Selivanova P.A., Kulikov E.S., Kozina O.V. et al. Differential expression of the #b2-adrenoreceptor and M3-cholinoreceptor genes in bronchial mucosa of patients with asthma and chronic obstructive pulmonary disease. Ann. Allergy Asthma Immunol. 2012; 108 (1): 39–43.</mixed-citation><mixed-citation xml:lang="en">Selivanova P.A., Kulikov E.S., Kozina O.V. et al. Differential expression of the #b2-adrenoreceptor and M3-cholinoreceptor genes in bronchial mucosa of patients with asthma and chronic obstructive pulmonary disease. Ann. Allergy Asthma Immunol. 2012; 108 (1): 39–43.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Kerstjens H.A.M., Engel M., Dahl R. et al. Tiotropium in asthma poorly controlled with standard combination therapy. N. Engl. J. Med. 2012; 367 (13): 1198–1207.</mixed-citation><mixed-citation xml:lang="en">Kerstjens H.A.M., Engel M., Dahl R. et al. Tiotropium in asthma poorly controlled with standard combination therapy. N. Engl. J. Med. 2012; 367 (13): 1198–1207.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Gosens R., Zaagsma J., Meurs H. et al. Muscarinic receptor signaling in the pathophysiology of asthma and COPD. Respir. Res. 2006; 7: 73.</mixed-citation><mixed-citation xml:lang="en">Gosens R., Zaagsma J., Meurs H. et al. Muscarinic receptor signaling in the pathophysiology of asthma and COPD. Respir. Res. 2006; 7: 73.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
