Метилглиоксаль что это такое в медицине

Влияние метилглиоксаля на течение острого повреждения легких у мышей при экспериментальном инфицировании вирусом гриппа A(H1N1)PDM09

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Аннотация

Цель исследования. Изучение влияния 2-оксопропаналя (метилглиоксаль) на течение вирус-индуцированного острого повреждения легких.

Материалы и методы. Исследование проведено на взрослых аутбредных самках мыши. Метилглиоксаль вводили подкожно в дозе 50 мг/кг/сут в течение 14 дней до инфицирования. С целью моделирования вирусной инфекции использовали штамм вируса гриппа A(H1N1)pdm09 в дозе, равной 0,75 расчетной величины LD₅₀. На 4, 7 и 14-е сутки после инфицирования выполняли гематологическое исследование цельной крови, патоморфологическое и гистологическое исследование легких. Степень поражения легочной ткани оценивали полуколичественным методом.

Результаты. Метилглиоксаль вызвал двукратное повышение летальности и площади поражения легких (р –3,4 в десятикратном разведении. Вирусная природа ОПЛ была подтверждена с помощью постановки реакции гемагглютинации. Легкие инфицированных животных гомогенизировали в физиологическом растворе. Гомогенат центрифугировали, отбирали супернатант, который вводили в аллантоисную полость куриных эмбрионов и инкубировали при 36 °C в течение 48 часов. Перед забором аллантоисной жидкости яйца охлаждали при температуре +4 °C в течение 3–4 часов. К забранному биоматериалу добавляли эквивалентный объем 1 % взвеси эритроцитов в физиологическом растворе. Присутствие вирусных частиц в материале было подтверждено образованием характерного зонтика [15].

В экспериментах по изучению влияния метилглиоксаля на течение ОПЛ животные были разделены на три группы: 1-я группа — интактные животные (n = 10); 2-я группа — инфицированные мыши, получавшие плацебо (n = 40); 3-я группа — инфицированные мыши, получавшие метилглиоксаль (n = 40). Вируссодержащий материал вводили интраназально в дозе, равной 0,75 расчетной величины LD₅₀, или 10 –3,5 в десятикратном разведении. Метилглиоксаль (Sigma-Aldrich, США) вводили в дозе 50 мг/кг/сут подкожно (п/к) в течение двух недель до инфицирования [16].

Забор крови для гематологического исследования осуществляли в эппендорфы с ЭДТА и анализировали по следующим параметрам: количество лейкоцитов, лейкоцитарная формула. Количество лейкоцитов определяли на автоматическом гематологическом анализаторе Abacus Junior Vet, лейкоцитарную формулу — в окрашенном по Романовскому – Гимзе мазке крови при микроскопировании. Макроскопическое и гистологическое исследование проводили на 4, 7 и 14-е сутки либо после смерти животного в ходе эксперимента. Ход гистологического исследования: подготовка фиксирующих жидкостей, отбор материала во время вскрытия, фиксация материала, вырезание кусочков фиксированного материала, уплотнение обезвоживанием кусочков и заливка в парафин, резка блоков на санном микротоме, окраска парафиновых срезов (гематоксилином и эозином), просмотр гистологических препаратов, описание препаратов, микрофотосъемка, изготовление отпечатков.

Степень поражения легочной ткани оценивали согласно методике, предложенной American Thoracic Society [17] и заключающейся в подсчете баллов согласно табл. 1 в 20 полях при увеличении ×400. Степень поражения оценивали по формуле

при этом учитывали параметры (A, B, C, D, E), указанные в табл. 1.

Оценка значимости гистологических показателей поражения легких в баллах

Lung injury scoring system by histological parameters

Источник

Роль конечных продуктов гликирования в патогенезе осложнений сахарного диабета

*Пятилетний импакт фактор РИНЦ за 2020 г.

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Введение Гликирование – это основная причина спонтанного нарушения структуры внутриклеточных и внеклеточных белков различных физиологических систем. В 0,1–0,2% случаев гликирование проходит по остаткам лизина и аргинина [1,2]. В некоторых зонах, где метаболизм белков лимитирован (например, в хрусталике глаза), степень их гликирования может повышаться в 10 раз [3]. На фоне сахарного диабета гликирование белков усиливается, что связано с повышением уровня глюкозы и производных сахаридов как в плазме крови, так и в поврежденных сосудах. Существует множество продуктов присоединения глюкозы к белкам тканей и жидкостей организма in vivo. Наиболее ранним продуктом присоединения глюкозы к белку является Nе–фруктозил–лизин (ФЛ), при медленной деградации которого образуются различные конечные продукты гликирования (КПГ). Выраженной способностью гликировать белки обладают соединения дикарбонила эндогенного происхождения, а также глиоксаль, метилглиоксаль и 3–дезокси­глюкозон. Они формируются при деградации гликированных белков, промежуточных метаболитов гликолиза и перекисного окисления липидов. Соединения дикарбонила напрямую реагируют с белками с образованием КПГ (рис. 1а). Экспериментальные и клинические данные свидетельствуют о том, что интенсивность гликирования под действием метилглиоксаля нарастает при диабете непропорционально увеличению концентрации глюкозы [4–7]. По–видимому, это обусловлено синтезом метилглиоксаля из триозофосфата, который накапливается в стенках сосудов вследствие гипергликемии (рис. 2) [8]. В наибольшем количестве в качестве конечных продуктов гликирования образуются гидроимидазолоны, которые являются производными остатков ар­ги­нина, подвергшихся модификации глиоксалем, ме­тилглиоксалем и 3–дезоксиглюкозоном (3–DG), – N?–(5–ги­дро–4–имидазолон–2–ил)орнитин (G–H1), N?–(5–ги­дро–5–метил–4–имидазолон–2–ил)орнитин (MG–H1) и N?–(5–гидро–5–(2,3,4–тригидрокси­бу­тил)–4–ими­дазолон–2–ил)орнитин и родственные струк­турные изомеры (3DG–H) (рис. 1б). Другими широко изученными КПГ являются N?–карбоксиметил–лизин (КМЛ) и N?–карбоксиэтил–лизин (КЭЛ), а также производные перекрестного связывания белков – пентозидин и глюкозепан (рис. 1 в–е) [2,9–12].

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