Применение ванн "BIOLONG" при различных заболеваниях

Биолонг — Астма

         ПОЧЕМУ ЛЕЧЕБНО-ОЗДОРОВИТЕЛЬНЫЕ ВАННЫ «БИОЛОНГ»

             ЯВЛЯЮТСЯ ЭФФЕКТИВНЫМ СРЕДСТВОМ ПРИ ЛЕЧЕНИИ

                                           БРОНХИАЛЬНОЙ АСТМЫ

Ю.В.Медведев

Бронхиальная астма продолжает оставаться одной из наиболее сложных и трудноразрешимых проблем современного здравоохранения. Значимость данной проблемы настолько велика, что в 1995 году была принята международная программа «GINA», направленная на координацию работ ученых разных стран с целью разработки наиболее эффективных методов борьбы с этим тяжелым недугом. Тем не менее распространенность бронхиальной астмы среди населения большинства стран продолжает расти, что заставляет искать новые, иногда нетривиальные методы ее лечения.

Астма является хроническим заболеванием дыхательных путей. Основным методом ее лечения в настоящее время является фармакотерапия, включающая базисную терапию, направленную на борьбу с основной причиной недуга – хроническим воспалительным процессом, развивающимся в дыхательных путях, а также сопутствующую терапию, предназначенную для облегчения симптомов заболевания. В первом случае наиболее широкое применение получили глюкокортикостероидные препараты, а во втором случае – препараты, направленные на восстановление проходимости бронхов (бронходилататоры, антихолнергические препараты, теофиллин).

Необходимость длительного использования глюкокортикостероидов при лечении бронхиальной астмы может вызвать нежелательные побочные эффекты, в частности развитие остеопороза, катаракты, нарушения работы в системе гипоталамус-гипофиз-недпочечники. По этой причине необходим поиск альтернативных методов лечения данного заболевания, исключающих или сводящих к минимуму возможности появления осложнений. Такой альтернативный метод, основанный на использовании лечебно-оздоровительных ванн «Биолонг», был разработан на базе Российского научного центра восстановительной медицины и курортологии. Ранее высокая эффективность ванн «Биолонг» была показана при лечении синдрома хронической усталости, дорсопатий, псориаса и ряда других заболеваний.

Для того, чтобы понять причины высокой эффективности ванн «Биолонг» при лечении астмы, необходимо остановиться на некоторых наиболее важных аспектах развития заболевания. Ключевым моментом, запускающим каскадное развитие ряда патологических изменений в тканях при бронхиальной астме, является появление альвеолярной гипоксии, сопровождающейся снижением парциального давления кислорода и ростом содержания углекислого газа в артериальной крови. Само появление альвеолярной гипоксии связано с протеканием в легочной ткани хронического воспалительного процесса, сопровождающегося выделением ряда цитокинов, вызывающих сужение просвета сосудистого русла и нарушающих процесс микроциркуляции в тканях. Последующее увеличение систолического давления в легочной артерии имеет компенсаторное значение, предназначенное обеспечить более полное насыщение артериальной крови кислородом и последующую доставку его тканям-потребителям. Однако подобный механизм, эффективный на ранней стадии легочной гипертензии, начинает давать сбои по мере ее развития. Кровь, минуя капилляры, во все возрастающем количестве начинает проходить через артерио-венозные анастомозы (шунты). В результате присутствующие в тканях хеморецепторы, отслеживающие газовый состав биологических жидкостей, продолжают посылать в координационный центр мозга по системе афферентной связи сигналы, свидетельствующие о продолжающейся гипоксии тканей. В ответ по каналам эфферентной связи поступают команды на дальнейшую активизацию работы сердечно-сосудистой и легочной систем для восстановления нормального газового состава в тканях. Возникает порочный круг, когда чем выше становится систолическое давление в легочной артерии, тем больше крови проходит через шунты, минуя капилляры, и тем меньше кислорода доходит до потребителей, что заставляет и дальше активировать исполнительную систему, уже неспособную обеспечить в полной мере ткани кислородом. Чтобы разорвать данный порочный круг, необходимо было найти новое нетривиальное решение. Таким решением может оказаться переход от традиционной фармакотерапии, часто осложняющейся тяжелыми побочными эффектами из за длительного применения глюкокортикостероидов, на бальнеотерапию, когда основной лечебный эффект достигается за счет воздействия химических и физических факторов проводимой водной процедуры на кожные покровы человека с последующим отсроченным эффектом на весь организм.

На возникновение и развитие бронхиальной астмы важное влияние оказывает состояние и функциональная активность ряда типов клеток, в первую очередь клеток, формирующих эпителий бронхов и эндотелий бронхиальных сосудов, а также альвеолоцитов, тучных клеток и легочных макрофагов. Все они относятся к нитрооксидпозитивным клеткам, т.е. все они продуцируют оксид азота. В последние двадцать лет появилось огромное число публикаций, свидетельствующих о том, что вырабатываемый в тканях оксид азота выполняет функцию универсального регулятора клеточного и тканевого метаболизма. Однако среди множества выявленных функций особо важную роль оксид азота играет в регуляции сосудистого тонуса, а также проходимости бронхов.

Эпителий бронхов является не только механическим барьером между воздушным потоком и элементами легочной ткани, но и выполняет ряд важнейших метаболических, биохимических и регуляторных функций. Он участвует в синтезе сурфактанта, покрывающего стенки бронхов и обеспечивающего облегченное ламинарное течение  воздуха в них. В эпителиальных клетках осуществляется синтез ряда биологически активных веществ, в частности гормонов, протеолитических ферментов, биогенных аминов, с помощью которых обеспечивается регулирование локальных клеточных процессов как в условиях физиологической нормы, так и в случае воспалительных реакций. В физиологических условиях неповрежденный эпителий вырабатывает ряд как бронхорасслабляющих, так и бронхоконстрикторных субстанций, обеспечивающих адекватный запросам организма газообмен в легких.  Повреждение эпителиального пласта увеличивает чувствительность мышечных клеток бронхов к констрикторным факторам и нарушает воздухопроходимость бронхов.

В настоящее время установлено, что в клетках эпителия бронхов содержится фермент, участвующий в синтезе оксида азота из аминокислоты аргинина — нейрональная форма нитрооксидсинтазы (nNOS). Синтезируемый эпителием оксид азота является одним из основных агентов, противостоящих констрикторным стимулам и обеспечивающим проходимость бронхов. Физиологические эффекты оксида азота связаны с его способностью регулировать внутриклеточную концентрацию ионов кальция и запускать кальцийзависимые биохимические реакции. Подобные эффекты реализуются за счет активации расположенной в цитоплазме растворимой гуанилатциклазы, превращающей гуанидинтрифосфат в циклический гуанидинмонофосфат (цГМФ). Последний выполняет роль посредника, вызывающего через систему G-киназ активацию Са2+-зависимого насоса эндоплазматического ретикулума. Координируя многие Са2+-зависимые обменные процессы, оксид азота участвует таким образом в регуляции цАМФ-зависимых реакций, поскольку от внутриклеточной концентрации ионов кальция зависит концентрация самого цАМФ. В результате происходит расслабление мышечных клеток бронхов и увеличивается их проходимость. В то же время вырабатываемый в альвеолоцитах II типа оксид азота регулирует синтез компонентов сурфактанта, снижение выработки которых ведет к переходу течения воздушного потока с физиологического ламинарного на патологический турбулентный.

При развитии воспалительного процесса в легких в плазме крови появляются провоспалительные цитокины и оксиданты, которые запускают синтез в клетках эпителия индуцибельной формы нитрооксидсинтазы (iNOS). В отличие от конститутивной формы фермента, производящей физиологические концентрации оксида азота, который выполняет в тканях важнейшие регуляторные функции, индуцибельная форма фермента продуцирует в тысячу раз больше оксида азота, в результате чего извращается его воздействие на ткани и он вместо регуляторного влияния начинает оказывать провоспалительный и цитотоксический эффект. Одновременно с этим резко увеличивается синтез супероксидного ион-радикала, который является одной из наиболее эффективных ловушек для оксида азота. В результате последующего их взаимодействия в тканях снижается концентрация оксида азота и ослабляется его расслабляющее влияние на бронхи, но вместо этого растет содержание продукта их взаимодействия – токсичного пероксинитрита, оказывающего повреждающее воздействие на все элементы клеточных структур, в первую очередь на клеточные мембраны. При этом симптомы бронхиальной астмы обостряются, а клетки оказываются в состоянии окислительного стресса.

Рассмотрим поведение клеток эндотелиальной выстилки легочных сосудов в условиях физиологической нормы и при бронхиальной астме. Клетки эндотелия также являются нитрооксидпозитивными, однако в них выявлена другая конститутивная форма изофермента – эндотелиальная нитрооксидсинтаза (eNOS). Вырабатываемый ферментом оксид азота является главным регулятором сосудистого тонуса. В условиях физиологической нормы в эндотелии поддерживается баланс между активностью ингибиторов и активаторов тонуса сосудов. Однако при гипоксии, которая всегда сопутствует бронхиальной астме, в эндотелиоцитах нарушается экспрессия eNOS, что повышает чувствительность легочных сосудов к констрикторным агентам (эндотелину или серотонину). Развивается легочная гипертензия, сопровождающаяся снижением выработки оксида азота клетками эндотелия и нарушением процесса микроциркуляции в ткани. Повышение гидростатического давления на сосудистую стенку и воздействие напряжения сдвига текущей крови на эндотелий вызывает его повреждение и развитие эндотелиальной дисфункции. В результате происходит запуск ряда патогенетических программ, сопровождающихся развитием артериальной гипертензии, увеличением агрегации тромбоцитов, изменением сосудистой стенки, способствующим прогрессированию атерогенеза.

При бронхиальной астме изменения в воздухоносных путях наблюдаются в первую очередь в мелких бронхах, в которых происходит основной процесс насыщения крови кислородом и удаления углекислого газа. При этом просвет бронхов сужается в 1.5 раза и в них появляются слизистые пробки, ограничивающие доступ кислорода к кровяному руслу. Это способствует развитию тканевой гипоксии. Если в условиях физиологической нормы альвеолоциты вырабатывают мало оксида азота за счет функционирования nNOS, то при бронхиальной астме наблюдается увеличение продукции оксида азота, главным образом за счет индукции iNOS, которая в физиологических условиях не проявляется. Увеличение выработки оксида азота выше физиологической нормы совпадает с увеличением частоты приступов. Выявлены циркадные колебания уровня оксида азота при бронхиальной астме. В частности, активность iNOS увеличивается в 4 часа, что совпадает со временем появления ночных приступов.

Важную роль в патогенезе бронхиальной астмы играют тучные клетки. Они являются обязательным элементом соединительной ткани, а в легких их содержание варьирует в пределах (1-7).106 клеток/г ткани. Особенно много их находится вблизи кровеносных сосудов. Тучные клетки вырабатывают большое количество разнообразных по природе и воздействию на окружающие ткани биологически активных веществ (по некоторым оценкам до 60 наименований), большинство из которых они накапливают в специальных гранулах (гистамин, серотонин, гепарин, брадикинин, лейкотриены, протеолитические ферменты, АТФ и т.д.). Некоторые продукты, например, оксид азота, они вырабатывают и выделяют в окружающее пространство постоянно. Тучные клетки выполняют важную роль по регулировании местного гомеостаза. Продуцируемые и выделяемые ими биологически активные вещества осуществляют локальную адаптацию соседних клеток к изменяющимся условиям внешней среды. Считается, что некоторые из вырабатываемых ими медиаторов играют основную роль в патологических изменениях в легких при астме. Выделяемые в этих условиях клетками провоспалительные цитокины вызывают активацию фермента фосфолипаза А2, в результате чего появляется арахидоновая кислота, которая под воздействием фермента 5-липоксигеназы превращается в нестабильный лейкотриен А4. Последний в тучных клетках и эозинофилах соединяется с аминокислотой цистеином и превращается в цистеиновые лейкотриены типа С4, Д4 или Е4 – наиболее активные бронхоконстрикторы, в 103 раз более эффективные по сравнению с гистамином. Активация легочных тучных клеток, сопровождающаяся выделением цистеиновых лейкотриенов из гранул, приводит к нарушению проходимости бронхов, развитию тканевой гипоксии и утяжелению симптомов заболевания.

Особо следует остановиться на роли макрофагов при бронхиальной астме. Они составляют от 4 до 8 % от форменных элементов клеток крови. Из кровяного русла они мигрируют в очаги воспаления. Там они активируются и начинают синтезировать и выделять в окружающую среду десятки биологически активных веществ, существенно изменяющих течение физиологических процессов в клетках. Основной задачей макрофагов является поддержание тканевого гомеостаза. Чужеродные для организма клетки или белки, а также поврежденные в процессе развития воспалительной реакции клетки подлежат уничтожению. Это осуществляется либо путем их фагоцитоза и последующего переваривания, либо путем выделения в окружающую среду токсичных для клеток продуктов. В качестве «химического оружия» макрофаги вырабатывают бинарную смесь двух газов: супероксидный ион-радикал и оксид азота. Первый способствует выходу ионов железа из белка-транспортера ферритина и тем самым запускает последующую аутокаталитическую реакцию разложения перекисей с образованием крайне токсичных для клеток гидроксильных радикалов. Оксид азота вырабатывается макрофагальной формой нитрооксидсинтазы в количествах, на три порядка превышающих физиологическую норму. В этих условиях оксид азота утрачивает важную для организма функцию координатора биохимических процессов соседних клеток, превращаясь в токсичный для них продукт. Активированные макрофаги, мигрирующие в зону воспаления, очищают ткани от поврежденных нежизнеспособных клеток. Однако выделяемые ими в окружающую среду токсичные молекулы повреждают и близко расположенные жизнеспособные клетки. Считается, что основные негативные проявления при бронхиальной астме связаны с гиперпродукцией оксида азота, преимущественно за счет активации индуцибельной формы NO-синтазы.

При использовании в Российском научном центре восстановительной медицины и курортологии лечебно-профилактических ванн «Биолонг» были получены обнадеживающие результаты при лечении бронхиальной астмы. С чем могут быть связаны причины успеха? Их может быть несколько. В первую очередь следует напомнить, что в процессе клинических испытаний «Биолонга» было установлено, что подобные бальнеологические процедуры восстанавливают или существенно улучшают кровоток и лимфоотток в тканях. Поскольку при бронхиальной астме наблюдается гипоксия тканей, восстановление в них процесса микроциркуляции, обеспечивающего своевременную доставку клеткам кислорода и питательных веществ, а также отвод отработанных продуктов метаболизма, будет способствовать оздоровлению организма.

Одной из причин, ответственной за нарушение кровотока при астме, может быть нарушение баланса между продуцируемыми эндотелием и ближайшим окружением вазоконстрикторами и вазодилататорами. Как известно, наиболее эффективным вазодилататором является оксид азота. Однако при заболевании бронхиальной астмой резко увеличивается выработка супероксидного ион-радикала. Этому способствует как менее эффективная работа в условиях гипоксии митохондриальной дыхательной цепи, так и появление в зоне воспаления активированных клеток-резидентов (макрофагов, нейтрофилов, эозинофилов, лейкоцитов). Из-за высокого сродства образовавшиеся ион-радикалы немедленно связывают оксид азота. Тем самым в кровотоке снижается концентрация последнего, что негативно влияет на тонус сосудов. Ранее нами было показано, что входивший в состав «Биолонга» препарат митофен, подобно специфическому ферменту супероксиддисмутазе, способен снижать концентрацию ион-радикала в тканях. В этом случае прием бальнеологических процедур с использованием «Биолонга» объясняет одну из возможных причин восстановления как микроциркуляции, так и воздушного потока в легких, а в результате и общего оздоравливающего воздействия подобных ванн на организм человека.

Стабилизация физиологической концентрации оксида азота вблизи тучных клеток благоприятно сказывается на их функционировании. Как известно, при ее снижении происходит ускоренное выделение биологически активных веществ из гранул, многие из которых, например гистамин и сериновые лейкотриены, обладают вазоконстрикторым действием. Принятие ванн «Биолонг» способствует восстановлению равновесия между синтезируемыми в тканях вазоконстрикторами и вазодилататорами, нарушаемому при бронхиальной астме, что положительно влияет на динамику лечения астмы.

Ранее было показано, что входящий в состав «Биолонга» митофен снижает хемилюминисценцию нейтрофилов, связанную с продукцией супероксидных ион-радикалов. Поскольку механизм активации различных клеток-резидентов общий, следует ожидать, что ванны «Биолонг» будут ингибировать экспрессию в макрофагах индуцибельной формы NO-синтазы и тем самым приближать концентрацию продуцируемого оксида азота к физиологической норме.

Древнегреческий врач утверждал, что лечить надо не болезнь, а человека. Бальнеологические процедуры на основе ванн «Биолонг» полностью удовлетворяют данному требованию. Через кожные покровы, имеющие на своей поверхности миллионы различных рецепторов и до 1700 биологически активных точек, связанных со всеми структурами организма, густую пронизывающую всю кожу капиллярную сеть, ванны «Биолонг» оказывают на организм комплексное оздоравливающее воздействие и в то же время исключают тяжелые побочные эффекты, характерные для стандартной схемы лечения бронхиальной астмы. По-видимому, в значительной степени высокая эффективность ванн «Биолонг» может быть связана как с антигипоксической и антиоксидантной активностью входящего в состав композиции митофена, так и со стабилизацией концентрации оксида азота в тканях – универсального регулятора клеточного и тканевого метаболизма, координирующего функционирование важнейших для тканей Са2+-, цАМФ- и цГМФ-зависимых метаболических процессов.

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