Influence of lithium chloride on the apoptosis of endotheliocytes in systemic inflammatory response syndrome in patients with severe multiple injury. A retrospective study
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lithium chloride
systemic inflammatory response syndrome
glycogen synthase kinase 3β

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Kuzovlev AN, Grebenchikov OA, Meshkov MA, Dolgikh VT, Prokofiev MD, Shpichko NP, Ershov AV Influence of lithium chloride on the apoptosis of endotheliocytes in systemic inflammatory response syndrome in patients with severe multiple injury. A retrospective study. Annals of Critical Care. 2020;(3):115–121. doi:10.21320/1818-474X-2020-3-115-121.


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Objectives. The goal is to study the effect of lithium chloride on the intensity of endotheliocytes apoptosis in a monolayer in vitro under the action of blood serum of patients with the syndrome of systemic inflammatory response in severe multiple trauma.

Materials and methods. We used toxic blood serum of 5 patients with severe multiple trauma. As controls we used blood serum of 5 healthy donors. In different series of the experiment EA.hy926 endothelial cells were incubated with blood serum of a healthy person (control), with blood serum of patients with systemic inflammatory response syndrome in severe multiple trauma. Lithium chloride was added to the cell samples at final concentrations of 0.01, 0.1, 1, 10 mmol/L. After incubation the cells were removed with trypsin-versen solution fixed with 70 % ethanol and stained with propidium iodide. Cells containing fragmented genomic DNA were analyzed by flow cytometry.

Results. It was revealed that toxic serum suppressed GSK-3β phosphorylation in endotheliocytes and also caused the splitting of VE-cadherin, a decrease in the amount of claudine and actin, initiating the destruction of intercellular contacts of the endothelial monolayer and apoptosis of endotheliocytes. Incubation of a monolayer of endotheliocytes with lithium chloride at a concentration of 1.0 mmol/l and higher almost completely prevented the dismantling of claudine, actin and VE-cadherin, and also reduced the intensity of apoptosis of endotheliocytes by more than 2 times. It was found that preincubation with lithium chloride at a concentration of 1 mmol/L not only prevented the inactivation of GSK-3β, but even stimulated its phosphorylation.

Conclusion. Lithium chloride prevents the dismantling of claudine and VE-cadherin in the intercellular contacts, reduces the number of apoptotic cells in the monolayer of the endothelial cells of the EA.hy926 line under the action of the blood serum of patients with a systemic inflammatory response syndrome in severe multiple trauma, which may indicate a protective effect of the drug on endothelial barrier. The results of this investigation suggest that the protective effect of lithium chloride on endothelium is realized via GSK-3β phosphorylation.
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