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Linagliptin alleviates fatty liver disease in diabetic db/db mice

World Journal of Diabetes 2016年第19期7卷 534-546页

作者： Svetlana V Michurina irina Ju ishenko Vadim V Klimontov Sergey A Archipov Natalia E Myakina Marina A Cherepanova Eugenii L Zavjalov Galina V Koncevaya vladimir i konenkov Laboratory of Functional Morphology Scientific Institute of Clinical and Experimental Lymphology Laboratory of Endocrinology Scientific Institute of Clinical and Experimental Lymphology SPF-vivarium Institute of Cytology and Genetics of Siberian Branch of Russian Academy of Sciences Laboratory of Clinical immunogenetics Scientific Institute of Clinical and Experimental Lymphology

AiM To study the effects of linagliptin on the structural signs of non-alcoholic fatty liver disease(NAFLD) in db/db mice. METHODS Male diabetic db /db mice(***-Dock7m+/+Leprdb/J) aged 10 wk received the dipeptidyl peptidase 4(DPP4) inhibitor linagliptin(10 mg/kg) or saline as a placebo once per day by gavage for 8 wk. intact db/db mice served as controls. Structural changes in the liver were analyzed from light and electron microscopic images of sections from intact, placebo-treated and linagliptin-treated animals. We estimated the changes in hepatocytes, sinusoidal cells, liver microvasculature and lymphatic roots. Hepatic staining for lymphatic vessel endothelial hyaluronan receptor-1(LYVE-1) was assessed by immunohistochemistry. RESULTS in 18-wk-old diabetic mice, liver steatosis(predominantly microvesicular and mediovesicular steatosis) was accompanied by dilation of the roots of the lymphatic system, interlobular blood vessels and bile canaliculi. Compared to saline-treated mice, linagliptin-treated mice exhibited a reduction in the mean numeral densities of hepatocytes with lipid droplets(92.4% ± 1.7% vs 64.9% ± 5.8% per field of view, P = 0.0002) and a lower proportion of hepatocytes with a high density of lipid droplets(20.7% ± 3.6% vs 50.4% ± 3.1%, P = 0.0007). We observed heterogeneous hepatocytes and relatively preserved cell structures in the linagliptin group. Dilation of blood and lymphatic vessels, as well as ultrastructural changes in the hepatocyte endoplasmic reticulum and mitochondria, were alleviated by linagliptin treatment. in intact and placebo-treated mice, immunohistochemical staining for LYVE-1 was observed in the endothelial cells of interlobular lymphatic vessels and on the membranes of some endothelial sinusoidal cells. We observed an enlarged LYVE-1 reaction area in linagliptin-treated mice compared to intact and placebo-treated mice. The improvement in the structural parameters of the liver in linagliptin-treated mice was independe

关键词： Diabetes Obesity Non-alcoholic fatty liver disease Dipeptidyl peptidase 4 Linagliptin

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TNF-α gene polymorphisms: association with age-related macular degeneration in Russian population

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international Journal of Ophthalmology(English edition) 2019年第1期12卷 25-29页

作者： Valeriy Chernykh Alla Shevchenko vladimir konenkov Viktor Prokofiev Alena Eremina Alexander Trunov Novosibirsk Branch S.Fyodorov Eye microsurgery Federal State Scientific institute of Clinical and Experimental Lymрhology

AiM: To study polymorphisms in promotor regions of tumor necrosis factor(TNF)-α TNF-863 A/C(rs1800630), TNF-308 A/G(rs1800629), and TNF-238 A/G(rs361525) in patients with age-related macular degeneration(AMD) and associations of complex TNF-α genotypes with AMD. METHODS: One hundred and two patients(82 women, 20 men; mean age 64.2±1.2 y) with AMD and 100 healthy age-and sex-matched controls(82 women, 18 men; 60±1.4 y) were included in the study. All subjects were Caucasian, all subjects and their parents were inhabitants of Russia. Genomic DNA was obtained from EDTA-preserved blood using the standard phenol-chloroform method. Polymorphisms were detected by polymerase chain reaction followed by the restriction fragment length polymorphism method. The following TNF-α genotypes were studied: TNF-α-238 AA, GA, GG, TNF-α-308 AA, GA, GG, TNF-α-863 AA, CA, CC. RESULTS: Differences in TNF-α-863 and TNF-α-238 genotypes frequencies in patients with AMD and healthy controls were not found. The distribution of TNF-α-308 AA and TNF-α-308 GA genotypes was significantly different between the studied group and the controls [odds ratios(OR) =0.22, P=0.0287 and OR=2.91, P=0.0063, respectively]. TNF-863 CC/TNF-308 GA and TNF-308 GA/TNF-238 GG genotypes were associated with the increased risk of AMD(OR=2.48, P=0.0332 and OR=2.51, P=0.0187, respectively). Five genotypes combinations appeared to be protective. CONCLUSiON: in the present study, single nucleotide polymorphisms and complex polymorphisms of one of the key inflammatory cytokines TNF-α, and a number of significant associations of these polymorphisms with AMD in Russian population have been shown. Complexanalysis of genotypes could be important in AMD risk factors detection and studying pathogenesis.

关键词： tumor necrosis factor-a genetic polymorphisms age-related macular degeneration

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Age and Gender Differences in Cytokine Profile of Lymph and Blood Serum

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Advances in Aging Research 2014年第3期3卷 216-221页

作者： Alexandr Poveshchenko Nikolai Orlov Oleg Kazakov Olga Poveshchenko irina Kim Natali Bondarenko Tatjana Miller Dmitri Strunkin Alexei Kabakov Tatjana Reiter vladimir konenkov FSBi Scientific institution of Clinical and Experimental Lymphology SB RAMS Novosibirsk Russia

We studied the cytokine profile (iL-1α, iL-1β, iL-2, iL-4, iL-6, iL-10, GM-CSF, interferon-γ, TNFα,) of the lymph, blood serum and conditioned medium of the lymph cells of Wistar rats. it was found that the concentration of cytokines investigated in the lymph of Wistar rats was significantly higher compared to the serum. Age and gender differences between the concentration of pro- and anti-inflammatory cytokines in the lymph and blood serum were found. The concentration of the cytokines was determined using the test system “Bio-Rad”.

关键词： Cytokines Lymph Blood Serum

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