ВЛИЯНИЕ СЕРОВОДОРОДА НА СОКРАТИТЕЛЬНУЮ АКТИВНОСТЬ МИОКАРДА ПРАВОГО ЖЕЛУДОЧКА КРЫСЫ

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ВВЕДЕНИЕ

Последние достижения в физиологии в основном связаны с расшифровкой механизмов межклеточных взаимодействий и регуляции деятельности клетки. Кроме исследования классических посредников прошлый век ознаменовался открытием физиологической роли некоторых общеизвестных газообразных веществ. Оказалось, что сигнальную функцию в межклеточной коммуникации и во внутриклеточной регуляции выполняют известные своими токсичными эффектами газы: сероводород (H2S), монооксид углерода (СO) и оксид азота (NO) [Wang, 2004].

Существует ряд параметров, которым должен соответствовать потенциальный газообразный посредник: его молекулы должны существовать в виде газа и беспрепятственно проникать сквозь мембраны клеток, он должен иметь источник эндогенного синтеза и ферменты синтеза, должен участвовать в регуляции физиологических функций, иметь специфические клеточные и молекулярные мишени [Wang, 2002]. Все известные и исследованные на данное время газотрансмиттеры соответствуют этим параметрам.

В окружающей среде H2S образуется, главным образом, при разложении органических веществ. Также он обнаруживается в природном газе, нефти и выбросе вулканической серы [Gadalla et al., 2010]. Как и все газотрансмиттеры, H2S является небольшой молекулой, которая может проходить через клеточные мембраны без использования конкретных переносчиков. Большая часть сероводорода метаболизируется в тиосульфат и сульфат в ходе окислительного процесса в митохондриях. Только низкие уровни H2S могут быть превращены в цитозоле клетки в менее токсичные соединения [Chen et al., 2004; Stipanuk et al., 2010]. С целью поддержания сбалансированного уровня H2S, его метаболические продукты удаляются в течение 24 часов через почки, желудочно-кишечный тракт (ЖКТ) и легкие

СОДЕРЖАНИЕ

стр.

СПИСОК СОКРАЩЕНИЙ

3

ВВЕДЕНИЕ

5

1   ОБЗОР ЛИТЕРАТУРЫ

9

1.1 Роль H2S в межклеточной коммуникации и регуляции

9

деятельности клетки

1.2 Взаимодействие NO, СО и H2S

14

1.3 Физико-химические свойства H2S

15

1.4 Образование и катаболизм H2S

16

1.5 Токсичность и эндогенные концентрации H2S

19

1.6 Физиологические и патофизиологические эффекты и механизмы

20

действия H2S

1.7 Патологические процессы, связанные с метаболизмом H2S

22

в организме

1.8 Роль H2S в сердечно-сосудистой системе

23

1.9 Влияние H2S на сократимость миокарда

26

1.10 Механизмы регуляции сократимости сердечной мышцы

28

ЭКСПЕРИМЕНТАЛЬНАЯ ЧАСТЬ

36

2    МАТЕРИАЛЫ И МЕТОДЫ

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2.1 Объект и методы исследования

36

2.2 Растворы и фармакологические вещества

38

3    РЕЗУЛЬТАТЫ И ОБСУЖЕНИЕ

40

3.1 Эффекты донора Н2S-NaHS на сократимость изолированной полоски миокарда желудочка

40

3.2 Роль К-каналов в отрицательном инотропном эффекте NaHS

41

в изолированной полоске миокарда

3.3 Роль NO в эффектах H2S на сократимость миокарда

43

3.4 Обсуждение результатов

45

ВЫВОДЫ

47

СПИСОК ИСПОЛЬЗОВАННЫХ ИСТОЧНИКОВ

48

СПИСОК ИСПОЛЬЗОВАННЫХ ИСТОЧНИКОВ

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