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Matrix metalloproteinases system in the chronic liver diseases

[Original research] [Internal diseases]
Pavel Koroy; Temirlan Ruslanovich Dudov; Alexandr Yagoda;

In the study evaluated the relationship of the matrix metalloproteinases (MMP) system components with the features of the chronic liver diseases (CLD) course. There are 240 patients with CLD of viral or alcoholic etiology aged 18 to 64 years was included in this study. Chronic hepatitis (CH) was detected in 81 patients, liver cirrhosis (LC) was diagnosed in 159 cases. 72 healthy people was included into the control group. The blood levels of MMP-1, MMP-9 and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) were determined; the ratio of TIMP-1/MMP-1, TIMP-1/MMP-9 was calculated. We was detected the increased levels of MMP-1 and TIMP-1 in the blood, the ratio of TIMP-1/MMP-9 and a decrease of MMP-9 and TIMP-1/MMP-1 in CLD. In patients with liver cirrhosis the parameters of TIMP-1, TIMP-1/MMP-1, TIMP-1/MMP-9 were higher, and MMP-9 were lower than in cases of chronic hepatitis. The risk of detecting cirrhosis in liver diseases increased 5 times at TIMP-1 levels above 547 ng/ml, 2 times – at MMP-1 levels less than 15.2 ng/ml, at MMP-9 levels below 154 ng/ml, at TIMP-1/MMP-1 values more than 36.5 and 3 times – with TIMP-1/MMP-9 values higher than 4.4. The imbalance in the matrix metalloproteinase system is associated with the course and severity of chronic liver diseases. The shift in the balance towards the predominance of TIMP-1 expression reflects the intensification of fibrogenesis processes, the maximum intensity of which was determined in cases of liver cirrhosis. В исследовании изучалась взаимосвязь компонентов системы матриксных металлопротеиназ (ММП) с особенностями течения хронических заболеваний печени (ХЗП). В исследование включено 240 больных ХЗП вирусной или алкогольной этиологии в возрасте от 18 до 64 лет. Хронический гепатит (ХГ) выявлен у 81 пациента, цирроз печени (ЦП) диагностирован в 159 случаях. 72 практически здоровых человека составили группу контроля. Определяли содержание в крови ММП-1, ММП-9 и тканевого ингибитора матриксных металлопротеиназ-1 (ТИМП-1), рассчитывали соотношение ТИМП-1/ММП-1, ТИМП-1/ММП-9. При ХЗП наблюдалось увеличение содержания ММП-1 и ТИМП-1 в крови, соотношения ТИМП-1/ММП-9 и снижение ММП-9 и ТИМП-1/ММП-1. У пациентов с циррозом печени показатели ТИМП-1, ТИМП-1/ММП-1, ТИМП-1/ММП-9 были выше, а ММП-9 – ниже, чем в случаях хронического гепатита. Риск обнаружения цирроза при патологии печени увеличивался в 5 раз при уровнях ТИМП-1 выше 547 нг/мл, в 2 раза – при величинах ММП-1 менее 15,2 нг/мл, ММП-9 ниже 154 нг/мл, ТИМП-1/ММП-1 более 36,5 у.е. и в 3 раза – при показателях ТИМП-1/ММП-9 выше 4,4 у.е. Дисбаланс в системе матриксных металлопротеиназ ассоциирован с течением и тяжестью хронических заболеваний печени. Смещение соотношения в сторону экспрессии ТИМП-1 отражает усиление процессов фиброгенеза, максимальная интенсивность которого определяется в случаях формирования цирроза печени.

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Keywords: chronic liver diseases, chronic hepatitis, liver cirrhosis, matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases


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Pyatigorsk State Research Institute of Balneotherapeutics
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