The Role of the Hepatic Tissue Remodeling Regulators MMP-9 and TIMP-1 in the Progression of Liver Cirrhosis

Introduction Cirrhosis of the liver is one of the leading problems of modern medicine in Russia and the world, the incidence of which tends to increase at the present time, and mortality among liver diseases with cirrhosis reaches 47%.The purpose of the work is to evaluate the significance of metalloproteinases (MMPs) and their inhibitors in the formation of liver fibrosis and cirrhosis in the outcome of chronic hepatosis of mixed toxic etiology and the use of OD in the experiment.Materials and methods In Wistar rats of group 1, posttoxic chronic hepatosis was induced by injections of 50% CCl4 oil solution intraperitoneally and 6.5% aqueous solution of ethyl alcohol per os for 60 days. Animals of the 2nd (experimental) group – against the background of the injections of toxic factors from the 30th day of the experiment, for the next 60 days intraperitoneally injected 2 ml of 5% aqueous solution of oxidized dextran (Mr 40 kDa). The numerical density of Kupfer cells, expressing MMP-2, MMP-9, TIMP-1 was studied in the liver.Results From the 60th day, group 1 rats developed cirrhosis of the liver with the formation of false lobules. With the injections of oxidized dextran, the number of Kupfer cells expressing MMP-2, MMP-9 was up to 2 times less than in group 1 rats. The numerical density of Kupfer cells expressing TIMP-1 in group 2 rats was 3 times higher on day 60 than in group 1 rats. In group 2 rats, by the 90th day, a decrease in the number of Kupfer cells expressing MMP-2, MMP-9 by 2 times, and TIMP-1 by 3 times was observed.Discussion OD in chronic toxic hepatosis has an antifibrotic effect that prevents the formation of liver cirrhosis, due to both the processes of collagen degradation in the extracellular matrix under the influence of MMP-2, MMP-9, and associated with a violation of the collagen assembly process, apparently due to the “blockade of the assembly” of tropocollagens by aldehyde-aldehyde bond with oxidized dextran.Conclusion The use of OD in chronic toxic hepatosis prevents the formation of liver cirrhosis in the experiment due to increased processes of collagen degradation in the extracellular matrix under the influence of MMP-2, MMP-9.

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Study of the role of metalloproteinases and their inhibitors in the formation of posttoxic fibrosis and cirrhosis and the use of oxidized dextran in the experiment

Karpov

Nadeev

Klochin

et al. 2023

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The Role of the Hepatic Tissue Remodeling Regulators MMP-9 and TIMP-1 in the Progression of Liver Cirrhosis

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Study of the role of metalloproteinases and their inhibitors in the formation of posttoxic fibrosis and cirrhosis and the use of oxidized dextran in the experiment

Study of the role of metalloproteinases and their inhibitors in the formation of posttoxic fibrosis and cirrhosis and the use of oxidized dextran in the experiment

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