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Overweight and obesity are among the main factors of cardiovascular risk, but the prospective studies on the dependence between high-fat diets and weight gain yielded contradictory results. Different types of fats exert varying metabolic effects, and this fact leads to a difference in the risk associated with increasing body weight. The effects of fat quality in the daily diet on immunological status and resistance of myocardium to ischemic-reperfusion damage should be studied experimentally in biomedical models. The purpose of this work was to assess the effect of the qualitative composition of a high-fat diet used for induction of primary visceral obesity (PVO) in rats with systemic inflammatory response syndrome (SIRS) upon myocardial resistance to ischemic-reperfusion injury, and levels of pro- and anti-inflammatory cytokines.The experiments were performed on adult male Wistar rats with PVO caused by 28-day consumption of any fat types: hydrogenated fats (HF), vegetable oils (VO), animal fats (AF) or milk fat (MF). The SIRS model included a combination of chemically induced colitis (CIC) and intragastric injection of a broad-spectrum antimicrobial agent (AMA) for three days. Five days later, immunological and biochemical studies were conducted, as well as composition of intestinal microbiota in faecal samples, morphological changes in the structure of the large intestine, hemodynamic parameters and myocardial resistance to ischemic-reperfusion injury were studied in the model of isolated heart perfusion, by Langendorff technique.There was a significant increase in the concentration of anti-inflammatory cytokines in animals with SIRS, i.e., TNFα, IL-1α, IL-2, IL-8, as well as a decrease in TGF-1β, an anti-inflammatory cytokine. SIRS was accompanied by severe dietary disorders and evacuatory function of the gastrointestinal tract. Minimal changes in the intestinal microbiota composition, as well as the most pronounced regeneration signs of intestinal epithelium was observed in rats in the group with MF injection. There was a trend for increasing size of infarction in all the groups as compared with control, directly correlating with increase in BDNF and IL-2 production. However, a significant increase in the infarction size was found only in the group receiving milkfat, thus suggesting a decrease in myocardial resistance to ischemic reperfusion injury (IRI).Thus, the presence of SIRS in the primary obesity model is characterized by controllable change of inflammation markers and depends on the quality of dietary fats. The degree of morphofunctional deterioration of isolated heart, including a decrease in resistance to ischemia-reperfusion injury, correlates with the concentration of BDNF and IL-2 during the studied observation terms.

Our objective was to develop a model of systemic inflammatory response syndrome (SIRS) by chemical induction of colon injury and antibiotic-associated intestinal dysbiosis in rats with primary visceral obesity (PVO) for studies of myocardial resistance to ischemia-reperfusion injury. The experiments were performed with adult Wistar male rats with PVO under improved conditions of a conventional animal clinic. The chemically induced inflammatory colon disease (CIICD) was accomplished by intragastric administration of a mixture of broad-spectrum antimicrobial agents (AMA) for 3 days. Five days later, immunological and biochemical studies were carried out, as follows: composition of the intestinal microbiota in feces and shortchain fatty acids in blood, morphological changes in the structure of the colon, hemodynamic parameters and myocardial stability with modified Langendorff system. In PVO rats, the mass of visceral fat deposits and the content of lipopolysaccharides (LPS) in the blood were significantly increased when giving them fatcarbohydrate diet (FCD). In animals with CIICD, in addition to LPS, there was a significant increase in proinflammatory cytokine concentration (TNF, IL-8, MCP-1), and after oral administration of the AMA mixture, pronounced disturbances of food behavior and evacuatory function of gastrointestinal tract, deep destructive changes in colon, as well as qualitative and quantitative composition of intestinal microbiota with characteristics typical to the first-grade dysbiosis. High levels were shown for IL-8 cytokine only. An increase in acetic and propionic acid concentrations were shown in blood in animals with CIICD, and, to a greater extent, in rats with antibiotic-induced dysbiosis (AID). FCD was followed by significantly reduced levels of lactobacilli and bifidobacteria in colonic contents. CIICD leads to detection of Escherichia coli, and intestinal dysbiosis leads to the manifestation of Proteus. A comorbid combination of pathological changes in the immune and digestive systems caused a significant increase in the area of myocardial necrosis (by 35 percent) in isolated heart by, thus presuming decreased myocardial resistance to ischemia-reperfusion injury (IRI). The SIRS model induced by chemical trauma to large intestine is aggravated by the introduction of AMAs mixture, and it is characterized by a controlled change in inflammatory markers. Deterioration of morphofunctional characteristics in isolated heart included decrease in resistance to IRI seems to correspond to acute inflammatory bowel disease with induced intestinal dysbiosis. This model can be used in experimental medicine in the field of cardiology, endomicroecology, gastroenterology, and immunology.

Modulatory effects of three probiotic bacterial strains (Lactobacillus rhamnosus K32 (L), Bifidobacterium longum GT15 (B, Enterococcus faecium L-3 (E) on expression level and contents of key cytokines were studied using PCR techniques with reverse transcription, and enzyme-linked immunosorbent assay. Both cell cultures and an experimental model of intestinal dysbiosis were used in this study. The genes encoding bacteriocins, surface membrane component, pili and exopolysaccharides involved in host immune system modulation were previously identified in the B and Ebacterial strains. Investigation of probiotic strains and effects of their supernatants expression of cytokines in cell cultures of promonocyte origin (HTP-1) showed increased expression of TNFα, due to E and L supernatants. Moreover, the Bl culture induced IL-8 and IL-10 expression. In a model of Wistar rats with ampicillinand metronidazole-induced intestinal dysbiosis corrected with probiotics we have shown that the dysbiosis was accompanied by sufficient alterations in microbiota composition (Klebsiella spp. overgrowth and low contents of Faecalobacterium prausnitzii) that were observed only in the animals untreated with probiotics (control), or after administration of L. In contrast to these results, the animals treated with E and B, the following changes were revealed: 1) low expression of proinflammatory cytokines IL-8, TNFα, MCP-1 inmesenteric lymph nodes and appropriate changes of their serum contents, 2) increased serum content of the anti-inflammatory TGFβ cytokine. Hence, the present study, having used two complementary models, has detected some individual features of immune modulation produced by the probiotictic strains of L. rhamnosus K32, B. longum GT15 и E. faecium L-3 which exert differential effects upon the intestinal microbiota.