Элементы биологической целесообразности стресc–реакции

Изменения, возникающие при интенсивной стрессовой реакции, трудно отнести к адаптационным. Поэтому их характеризуют как патологический стресс или, иначе, дистресс. Вместе с тем, трудно себе представить, чтобы стандартная адаптационная реакция на необычные ситуации, потенциально угрожающие организму, была бы столь биологически нецелесообразной. Рассмотрим её элементы.

Стресс высокой интенсивности приводит к апоптотической гибели большей части тимоцитов. К действию глюкокортикоидов, как отмечалось выше, наиболее чувствительны кортикальные тимоциты фенотипа CD4CD8, не экспрессирующие протоонкоген Вс1–2. Это определило их первоначальное название как чувствительные к кортизону клетки. Именно среди этой популяции тимических клеток и содержатся потенциально аутоагрессивные, не прошедшие отбор T–лимфоциты. При повреждении зоны тимуса они могут выйти в кровь или окружающие ткани и нанести существенный вред организму (а встреча с инфекцией может и не состояться). Высокая концентрация ГКС предотвращает такой вариант развития событий.

К действию ГКС, индуцирующих апоптоз, высоко чувствительны T–киллеры и NK, то есть клетки-эффекторы противовирусного иммунитета. Стратегия иммунной защиты от внутриклеточных паразитов заключается не в нейтрализации патогена, а в разрушении инфицированной клетки вместе с инфекционным агентом. Повреждение, вызванное клетками–киллерами, является обязательной платой за выздоровление при болезнях вирусной этиологии [59]. Одновременное разрушение большого массива поражённых вирусом клеток может нанести существенный вред организму [72]. Яркий пример вреда, который может нанести противовирусный иммунный ответ, проиллюстрирован следующими данными. Мышей заражали внутричерепным введением вируса лимфоцитарного хориоменингита. У нормальных инфицированных животных после этого возникает острое воспаление сосудистого сплетения, эпендимы, мягкой и паутинной оболочек мозга. Мыши погибали через 6–8 дней от полного разрушения ткани мозговых оболочек. Иммуносупрессированные мыши, заражённые этим вирусом, по продолжительности жизни не отличались от незаражённых, хотя в течение всей жизни в их мозговых оболочках обнаруживали персистенцию вируса. При введении таким животным нормальных T–клеток они быстро погибали от изменений, характерных для лимфоцитарного хориоменингита. Очевидно, что цитотоксические лимфоциты, специфичные к использованному вирусу, вызывают разрушение клеток, содержащих этот вирус, что приводит к разрушению мозговых оболочек. Вероятно, интенсивный синтез АКТГ, индуцируемый вирусной инфекцией, является одним из механизмов регуляции, сдерживающим развитие противовирусного иммунитета и уменьшающим тем самым интенсивность повреждения.

Биологически целесообразной является, по-видимому и конечная стадия стресса — стадия истощения. Как отмечалось выше, в основе стресc–реакции лежит гиперпродукция ГКС. Чем продолжительнее стресс и выше уровень гормонов, тем более выражено не только угнетение функций лимфоцитов, но и повреждение других тканей. Повышенное содержание в крови ГКС сопровождается подавлением воспалительной реакции, задержкой заживления ран, развитием некроза. Вызываемое ГКС повышенное выделение с мочой азотсодержащих соединений свидетельствует о распаде тканевых белков, что может привести к атрофии скелетных мышц, истончению эпидермиса, распаду эпителиальных клеток соединительной ткани. Длительный интенсивный стресс заканчивается стадией истощения. Надпочечники уменьшаются в размерах, значительно снижается содержание ГКС в крови. Эта стадия, вероятно, является необходимым условием для восстановления повреждений, полученных организмом как в результате действия факторов, вызвавших стресс, так и самого стресса. Снижение уровня ГКС в стадии истощения сопровождается нормализацией синтеза белков, восстановлением барьерной функции, уменьшением уровня апоптотической гибели клеток. Усиливается миграция стволовых клеток из костного мозга (глава 3 «Миграция стволовых клеток, T– и B–лимфоцитов», раздел «Контроль рециркуляции стволовых клеток»). Их поступление с кровотоком в повреждённую ткань способствует её восстановлению. Иначе говоря, несмотря на высокую чувствительность организма в стадии истощения к действию повреждающих факторов, в благоприятных условиях эта стадия стресса способствует восстановлению повреждённых органов и систем.

Таким образом, при интенсивной стресc–реакции организм, для того чтобы все силы направить на преодоление опасности, угрожающей жизни в данный момент, приостанавливает действие клеток-эффекторов, развитие противовирусного иммунитета, способного нанести вред организму. Одновременно с этим, в стадии истощения, возникают условия для нормализации нарушенных функций. Эти рассуждения подводят нас к мысли о том, что деление на физиологический и патологический стрессы, стресс и дистресс в значительной мере условно. Стресc–реакция — это один из механизмов физиологической реакции организма на чрезвычайные обстоятельства [84]. Цель реакции — избежать опасности, угрожающей жизни в данный момент. Стресс — это один из механизмов, с помощью которых все системы жизнеобеспечения направляются на достижение этой цели.

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