MORPHO-FUNCTIONAL CHARACTERISTICS LIVER OF RATS IN EARLY DEVELOPMENT OF STREPTOSOTOCIN DIABETES MELLITUS USING CLUSTER ANALYSIS
Keywords:liver, hepatocyte, streptozotocin-induced diabetes mellitus
One of the complications of diabetes mellitus (DM) is diabetic hepatopathy which, according to various authors, is diagnosed in 33–88% of patients. Therefore, the aim of our study was to establish the features of morphofunctional changes in the liver of 12-month rats at experimental streptozotocin-induced diabetes mellitus (ESDM) using cluster analysis. Used histological, histochemical, electron microscopic, biochemical and statistical research methods.
Analyzing histological microphotographs, we saw that in the hepatic lobe along the liver plate are hepatocytes, which are different in size of cells and nuclei. Therefore, we performed a quantitative analysis of hepatocytes in different areas of the liver lobe, taking into account the morphometry of only mononuclear cells. Using the mvoutlier package of the software environment R and the method of hierarchical tree-like clustering of Ward, 3 clusters (C) of cells were selected for analysis. In the control group of rats were found hepatocytes C1 which have the largest cell and nucleus area and a small nuclear-cytoplasmic ratio (NCR), and hepatocytes C3 was characterized by a small cell area, a large nucleus area and the largest NCR, C2 — medium-sized cells with a small nucleus and small NCR. The largest number of hepatocytes is C3 (45.68%), and the smallest — C1 (21.62%), C2 — 32.71%. It was found that hepatocytes C1 are located mainly in the peripheral zone of the liver, C2 and C3 are located in the central and intermediate zone.
In the early stages of the development of ESDM (14–28 days), the levels of glucose and HbA1c in the blood of animals significantly increase 3.1–3.4 times and 3.0–3.6 times (in all cases р < 0.05). In animals we observed regular changes in the morphometric parameters of hepatocytes of different clusters (C), namely: there was a decrease in the area of hepatocytes, which is associated with marked processes of glycogenolysis, that are confirmed by histological and ultrastructural studies. The area of nuclei of hepatocytes of different clusters decreases (in all cases р < 0.05). On the 14th day of ESDM the number of hepatocytes in C1 decreased by 3.64%, while in C2 it increases by 5.37%, while on the 28th day in C2 it decreases by 3.69%, while in C3 it increases by 4.81% (in all cases р < 0.05), indicating an increase in the pool of young hepatocytes and compensatoryregenerative processes of the liver.
In the early stages of ESDM, there is a significant increase in the activity of aminotransferases in both plasma and liver homogenates, as compared with the control group, but the De Ritis ratio does not statistically differ from the control indicators, showing the development of compensatory processes in the liver and preserving its complete functional capacity.
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