magistrsko delo
Peter Slatinšek (Author), Saška Lipovšek Delakorda (Mentor), Andraž Stožer (Co-mentor)

Abstract

Zahodnjaška prehrana pogosto vodi v pojav debelosti, presnovnega sindroma in sladkorne bolezni tipa 2. Predvsem slednja povzroča številne zgodnje patološke spremembe ledvic, ki lahko vodijo v kronično ledvično bolezen. Da bi preučili vpliv zahodnjaške prehrane na pojav in razsežnost patoloških sprememb celic proksimalnih in distalnih tubulov ledvic v novem mišjem modelu za sladkorno bolezen tipa 2, smo mišim C57BL/6J, hranjenim z zahodnjaško prehrano osem tednov, in kontrolnim mišim, hranjenim z normalno prehrano, izolirali ledvice in izdelali tkivne rezine. Le-te smo pregledali s svetlobno in transmisijsko elektronsko mikroskopijo (TEM) ter primerjalno ocenili strukturne spremembe ledvičnih tubulnih celic. Ugotovili smo, da je struktura tubulnih celic miši, hranjenih z zahodnjaško prehrano, drugačna od strukture celic kontrolnih miši. V pregledanih epitelijskih celicah proksimalnih in distalnih tubulov miši, hranjenih z zahodnjaško prehrano, so bile prisotne številne ovalne in okrogle temne strukture ter lipidne kaplje. Rezultate smo potrdili s TEM, pri čemer smo lahko analizirali strukturne spremembe pri večji ločljivosti, pri kateri smo opazili značilno plastovitost elektronsko temnih struktur. V celicah miši, hranjenih z zahodnjaško prehrano, smo nadalje opazili mitohondrije z neobičajno strukturo, povečano vakuolizacijo citoplazme ter številne avtofagne strukture: fagoforje, avtofagosome in avtolizosome. Zrnati endoplazemski retikulum ter Golgijev aparat sta bila spremenjena v nekaterih celicah; lumen njunih cistern je bil neobičajno širok. V proksimalnih in distalnih tubulih tretirane skupine miši so prav tako bile prisotne številne nekrotične celice s fragmenti organelov. Kljub temu da številni avtorji v raziskavah, opravljenih na ljudeh in živalih, opisujejo povezavo med sladkorno boleznijo tipa 2 in pojavom ne fropatoloških sprememb v tubulnih celicah ledvic, je mehanizem nastanka opisanih morfoloških sprememb še vedno neznan. V naši raziskavi smo potrdili prizadetost teh celic v novem mišjem modelu za sladkorno bolezen tipa 2, na podlagi česar predlagamo nadaljnje raziskave, s pomočjo katerih bi lahko pojasnili patofiziološke temelje in identificirali potencialne terapevtske tarče.

Keywords

magistrska dela;glomerul;proksimalni tubul;distalni tubul;kopičenje lipidov;avtofagija;nefropatija;

Data

Language: Slovenian
Year of publishing:
Typology: 2.09 - Master's Thesis
Organization: UM FNM - Faculty of Natural Sciences and Mathematics
Publisher: [P. Slatinšek]
UDC: 612.46:616.379-008.64(043.2)
COBISS: 24141576 Link will open in a new window
Views: 765
Downloads: 140
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Other data

Secondary language: English
Secondary title: Comparison of kidney structure of control mice and mice on western diet
Secondary abstract: The Western diet often leads to the development of obesity, metabolic syndrome, and type 2 diabetes. Particularly the latter causes many early pathological changes in the kidneys, which can result in chronic kidney disease. To evaluate the influence of the Western diet on the occurrence and the extent of pathological changes in cells of the proximal and distal kidney tubule in a novel model of type 2 diabetes, we fed C57BL/6J mice with a Western diet for 8 weeks and a control group of mice with the regular chow. We isolated the kidneys, prepared tissue slices, analyzed them with light and transmission electron microscopy, and comparatively evaluated the structural changes in renal tubular cells. We concluded that the tubular cell structure of mice fed with the Western diet is different from the structure of cells in the control mice. In the analyzed epithelial cells of proximal and distal tubules of mice fed with the Western diet, we noticed the presence of several oval- and circular-shaped dark structures, and lipid droplets. We used TEM to confirm these findings. The latter allowed us to analyze the structural changes at a higher magnification and gave insight into the multilaminar nature of the electron dense inclusions. In the cells of Western diet fed mice, we also noticed unusually structured mitochondria, with elevated vacuolization in the cytoplasm as well as several structures indicating autophagy: phagophores, autophagosomes, and autolysosomes. Additionally, in some cells the rough endoplasmic reticulum and Golgi apparatus displayed enlarged lumina of their cisterns. Finally, we noticed the presence of several necrotic cells with fragments of organelles in proximal and distal tubules. Although a number of studies in humans and animal models point to a connection between type 2 diabetes mellitus and nephropathological changes in kidney tubular cells and despite the fact that in our study we confirmed that these cells are affected in a novel mouse model of type 2 diabetes mellitus, the exact mechanism that underlies these morphological changes remains to be fully examined. Further research is needed to explain the pathophysiological basis and identify potential therapeutic targets.
Secondary keywords: master theses;glomerulus;proximal tubule;distal tubule;lipid accumulation;autophagy;nephropathy;
URN: URN:SI:UM:
Type (COBISS): Master's thesis/paper
Thesis comment: Univ. v Mariboru, Fak. za naravoslovje in matematiko, Oddelek za biologijo
Pages: [47] f.
ID: 10979062