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| 1 | Linagliptin alleviates fatty liver disease in diabetic db/db mice显示文摘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(BKS.Cg-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 independent to changes in the plasma glucose levels. CONCLUSION The DPP4 inhibitor linagliptin alleviates liver steatosis and structural changes in the hepatic microvasculature and lymphatic roots in a model of NAFLD in diabetic db/db mice. | 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 | 2016 | World Journal of Diabetes2016，7，19： | 2 |
| 2 | Study of the governing law of micro-arc oxidation and filling of MAO-coatings on aluminum alloys with the use of proton NBS spectrometry显示文摘 | BESPALOVA 0 V BORISOV A M MICHURINA V P | 2003 | Fizikai Khimiya Obrabotki Materialov2003，，： | 1 |
| 3 | The influence of experimental desynchronosis on the morphofunctional characteris- tics of mouse immune system显示文摘 | Trufakin VA Shurlygina AV Michurina SV | 2007 | Alaska Med2007，49，2： | 1 |
| 4 | Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippoeampus显示文摘 | Encinas J M Michurina T V Peunova N | 2011 | Cell Stem Cell2011，8，5： | 1 |
| 5 | Mesenchymal and haematopoietic stem cells form a unique bone marrow niche 显示文摘 | M6ndez-Ferrer S Michurina TV Ferraro F | 2010 | Nature2010，466，7308： | 1 |
| 6 | Study of the governing law of micro-arc oxidation and filling of MAO-coatings on aluminum alloys with the use of proton NBS spectrometry显示文摘 | Bespalova O V Borisov A M Michurina V P | 2003 | Fizi-kai Khimiya Obrabotki Materialov2003，，1： | 1 |
| 7 | Mesenchymal and hematopoietic stem cells form a unique bone marrow niche显示文摘 | Méndez-Ferrer S Michurina TV Ferraro F | 2010 | Nature2010，466，7308： | 1 |
| 8 | The in- fluence of experimental desynchronosis on the morphofune tional characteristics of mouse immune system显示文摘 | Trufakin VA Shurlygina AV Michurina SV | 2007 | Alaska Med2007，49，2： | 1 |
| 9 | Genetic approaches identify adult pituitary stem cells 显示文摘 | Gleibennan AS Michurina T Encinas JM | 2008 | Proc Natl Acad Sci2008，105，17： | 1 |
| 10 | Mesenchymal and haematopoietic stem cells form a unique bone marrow niche显示文摘 | Mendez-Ferrer S Michurina TV Ferraro F Mazloom AR Macarthur BD Lira SA Scadden DT Ma'ayan A Enikolopov GN Frenette PS | | 0，，： | 1 |
| 11 | Mesenchymal and haematopoietic stem cells form a unique bone marrow niche显示文摘 | Mendez-Ferrer S Michurina TV Ferraro F | | 0，，7308： | 1 |
| 12 | Mesenchymal and haematopoietic stem cells form a unique bone marrow niche 显示文摘 | M:ndez-Ferrer S Michurina TV Ferrare F | 2010 | Nature2010，466，7308： | 1 |
| 13 | Division-coupledastrocytic differentiation and age-related depletion of neural stemcells in the adult hippocampus显示文摘 | Encinas JM Michurina TV Peunova N | 2011 | Cell Stem Cell2011，8，5： | 1 |
| 14 | Mesenchymal and haematopoietic stem cells form a unique bone marrow niche 显示文摘 | Mendez - Ferrer S Michurina TV Ferraro F | 2010 | Nature2010，7308，： | 1 |
| 15 | Mesenchymal and haematopoietic stem cells form a unique bone marrow niche显示文摘 | Méndez-Ferrer S Michurina TV Ferraro F | 2010 | Nature2010，466，7308： | 1 |
| 16 | Studies on clonogenic hemopoietic cells of vertebrate in space: problems and perspectives显示文摘 | Domaratskaya EI Michurina TV Bueverova EI | 2002 | Adv Spase Res2002，30，4： | 1 |
| 17 | Study of the governing law of micro?arc oxidation and filling of MAO?coatings on aluminum alloys with the use of proton NBS spectrometry显示文摘 | Bespalova O V Borisov A M Michurina V P | 2003 | Fizi?kai Khimiya Obrabotki Materialov2003，，1： | 1 |
| 18 | Blood and clonogenic hematopoietic cells after the space flight显示文摘 | Domaratskaya EL Nikonova TM | 1996 | Adv Space Res1996，17，67： | 1 |
| 19 | Normal distribution and me- dullary-to-cortical shift of Nestin-expressing cells in acute renal is- chemia显示文摘 | Patschan D Michurina T Shi HK | 2007 | Kidney Int2007，71，8： | 1 |
| 20 | Mesenchymal and haematopoietic stem cel s form a unique bone marrow niche显示文摘 | Méndez-Ferrer S Michurina TV Ferraro F | | 0，，7308： | 1 |
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