RU2359338C1 - Arterial hypertension simulation method - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to experimental medicine, namely to experimental cardiology and can be used for arterial hypertension simulation to research its formation and development mechanisms, risk factors, and further to develop and implement current methods of preventive treatment. It is ensured by introduction of macro- and microcells to organism of nonlinear rats into water-dietary intake herewith introducing the foodstuff of the habitation subregion considered as unfavourable for arterial hypertension diagnosis. Development of arterial hypertension is observed from prepathological shifts of lipid exchange combined with blood pressure increase in animal.

EFFECT: simulation of biogeochemical arterial hypertension.

11 tbl, 1 dwg

Description

The invention relates to medicine, namely to experimental preventive medicine, and can be used to study the mechanisms of formation, development of risk factors and the further development, implementation of modern methods of preventive treatment of arterial hypertension.

Known methods for modeling various diseases in laboratory animals by introducing various chemicals into their bodies, for example, a method for modeling focal myocardial damage. To implement this method, a 5% solution of calypsol at a dose of 0.065 mg per 100 g of weight, and then a 0.1% solution of adrenaline hydrochloride at a dose of 0.5 mg per 100 g of body weight of the animal are pre-intraperitoneally administered to a laboratory animal. The method provides a model of multiple focal myocardial injuries in both acute and chronic experiments, without increasing the mortality of experimental animals, it is possible to achieve more pronounced changes in the myocardium, which makes it possible to more fully estimate the magnitude and prevalence of lesions by light microscopy, and increase the total area necrosis allows you to better study the processes of damage and repair, as well as the effects of drugs (see patent No. 2286606, G09B 23/28).

Known methods for modeling intracranial hypertension in laboratory animals by occlusion of the sigmoid sinus, however, these methods are highly traumatic and lead to slight diffuse changes in the nervous tissue (see Kurokawa Y., Hashi K., Okuyama T., Uede T. Regional ischemia in cerebral venous hypertension due to embolic occlusion of the superior sagittal sinus in the rat. Surg Neurol 1990 Dec; 34 (6): 390-5).

A known method of modeling intracranial hypertension by intracerebroventricular injection of 10 μg of neuroaminidase (see Grondona JM, Perez-Martin M., Cifuentes M., Perez J., Jimenez AJ, Perez-Figares JM, Fernandez-Llebrez P. Ependymal denudalite and aquedument hydrocephalus after a single injection of neuraminidase into the lateral ventricle of adult rats. J. Neuropathol Exp Neurol. 1996 Sep; 55 (9): 999-1008).

However, this method leads to high mortality of laboratory animals and does not cause a clinic of communicating hydrocephalus.

There is also a method for simulating intracranial hypertension by intracerebroventricular injection of 0.05 ml of a 25% solution of kaolin (see Tashiro Y., Drake JM, Chakrabortty S., Hattori T. Functional injury of cholinergic, GABAergic and dopaminergic systems in the basal ganglia of adult rat with kaolin-induced hydrocephalus. Brain Res 1997, Oct 3; 770 (1-2): 45-52).

However, the known modeling method leads to aseptic inflammation of the ventricular ependyma and, consequently, to the distortion of experimental data. This method leads to a slow development of occlusal hydrocephalus, which moves him away from the clinic of acute intracranial hypertension. The method leads to severe mortality of laboratory animals. The toxic effect of kaolin on nerve tissue leads to a distortion of experimental data. The known method does not allow to control the severity of clinical and morphological changes in laboratory animals.

The closest in technical essence is a method for modeling malignant arterial hypertension by introducing various chemicals into the body of experimental animals, thereby affecting the balance of biologically active substances in the animal body. Moreover, as experimental animals, 2-3-month-old SHR rats are used, and the balance of biologically active substances is infused dropwise 3 times with an interval of 2 days by introducing prostaglandin F2 ^α into the femoral vein at a dose of 1.25-1.5 μg 5 ml of a 5% glucose solution for 40-60 minutes (RU patent No. 2212059, IPC 7 G09B 23/28).

However, this method also leads to lethality of animals and is difficult to perform, and it does not reflect the dependence of the occurrence of arterial hypertension on biogeochemical factors, does not reflect changes in microelement homeostasis of the organism of laboratory animals, depending on biogeochemical factors that cause primary changes in the mammalian body.

The objective of the present invention is to provide a non-invasive method for simulating hypertension, simple in execution and preserving animals, while the task also includes creating, using the inventive method, a biogeochemical experimental model of arterial hypertension, most accurately reflecting changes in microelement homeostasis of the body of laboratory animals and subsequent violations of lipid and peroxide metabolism .

The technical result of the proposed modeling method is low morbidity, ease of implementation of the method, as well as the approximation of the model to the actual conditions for the occurrence of arterial hypertension in the environment, which is known as a dysfunctional environment in accordance with statistics on arterial hypertension.

This technical result is achieved by the fact that the simulation of arterial hypertension is carried out by introducing into the body of non-linear rats chemicals that affect the content of biologically active substances in their body, in the form of macro- and microelements. Modeling is carried out by introducing macro- and microelements into the organism of rats by using rats with water and feed taken from the subregion of human habitation, known as dysfunctional with respect to arterial hypertension. This water and feed contain trace elements that are qualitatively and quantitatively different from trace elements contained in the water and feed of the subregion of human habitation, which is favorable for arterial hypertension. Moreover, the development of arterial hypertension is judged by the occurrence of pre-pathological changes in lipid metabolism in combination with a simultaneous increase in blood pressure in animals.

The new set of features allows us to bring the model closer to the biogeochemical model of arterial hypertension, which most accurately reflects the changes in the microelement homeostasis of the organism of experimental animals, which are realized through primary shifts in the intestinal auto microflora with subsequent violations of lipid and peroxide metabolism. The proposed modeling method is simple in technical reproduction and accurately reflects the pre-pathological changes in the body of experimental animals. Nonlinear rats as the most accessible biological species can be used to create the model.

To implement the method, the level of trace elements (ME) in drinking water, feed and biomaterials (urine, blood serum, tissues of the internal organs: heart, aorta, liver, kidneys, small intestines) was determined by direct atomic absorption spectrometry (Ermachenko L.A. Atomic absorption analysis in sanitary-hygienic research: Methodological manual. - Cheb. ChSU. 1997 - 220 p.). The method is based on the ability of trace elements to absorb ultraviolet rays with a wavelength of 285-295 nm after the deposition of sample proteins using thermocoagulation. For each element being determined, a resonance radiation source was used, the element being determined was transferred to the elementary state by atomization (t - 2000-3000 ° C), to obtain a quantitative result, a series of preliminary measurements was carried out, according to which a calibration curve was constructed. Preliminarily, sample preparation was carried out by the autoclave mineralization method in the ANKON-AT-2 autoclave. The method is based on the complete mineralization of the sample with a mixture of nitric acid and hydrogen peroxide in the reaction chamber of the autoclave.

The resulting samples were weighed to the nearest 1 mg, placed in sterile tubes and stored at a temperature of -18 ° C. For the study of trace elements used atomic absorption spectrometer "Quantum - Z. ETA". The advantages of this method are high sensitivity and selectivity, a low probability of coincidence of the spectral lines of different elements, and therefore higher selectivity of the determinations.

The determination of the amount of iodine and fluorine was carried out by the ion-selective method using the Expert-1 instrument, designed to measure activity (PX, Ph), mass concentration of ions (C), (E), and the redox potential. The value was measured by the potentiometric method using ion-selective electrodes, which consists in measuring the potential difference of the electromotive force of the measuring electrode and the reference electrode. For analysis, at least 100 ml of water from the studied territories was taken. The chemical composition of water was evaluated three times during the experiment (autumn, winter, spring).

The determination of chlorides, sulfates, and total water hardness was carried out by the titrometric method.

During the experiment, a quarterly measurement of blood pressure (BP) was performed in rats of both groups by the blood method (Georgieva S.A., Belikina N.V. Physiology. - M .: Medicine. 1981, p. 191-192). Blood pressure was recorded with a mercury manometer in an occlusal manner from the femoral artery. To do this, an incision was made in the artery wall, through which a plastic peripheral catheter No. 24 was inserted using a conductor. The catheter using ligatures was strengthened in a vessel and connected to one end of the mercury manometer using a system of rubber and glass tubes filled with a solution that prevents blood coagulation. At the other end of the manometer, a float with a scribe was lowered. Pressure fluctuations were transmitted through the liquid of the tubes to a mercury manometer and a float, the movements of which were recorded on the surface of graph paper of a kimograph drum. When implementing this technique, we focused on literature data on which the blood pressure of most rats recorded from the femoral artery is 100-130 mm Hg. (Zapadnyuk I.P., Zapadnyuk V.I., Zakharia E.A. Laboratory animals. Kiev. 1974, p.204-209). Measurements were carried out with caution under inhalation ether anesthesia.

The daily amount of urine was collected in the generally accepted way using exchange cells (Zapadnyuk I.P., Zapadnyuk V.I., Zakharia E.A. Laboratory animals. Kiev. 1974, p.204-209).

Blood was drawn from the tail vein by cutting off the tip of the tail. The state of lipid metabolism in experimental animals was evaluated according to the results of studies of total cholesterol, lipoproteins and triglycerides according to the standardized methodology of the Center for Preventive Medicine of the RAMS (Moscow) (Kolb V.G., Kamyshnikov BC Handbook of Clinical Chemistry. - Minsk .: Belarus, 1982, - p. 98, 198, 206-208).

To implement the method, 30 non-linear male rats with an initial body weight of 148.0 ± 7.0 g were used. Animals were kept on feed and drinking water (in accordance with feeding standards) brought from two settlements of the Chuvash Republic (CR).

For the control group of 15 animals, fodder and water from the village of Turmyshi in the Yantikovsky district of the Chuvash Republic, which is part of the Prikubninotsivilsky biogeochemical subregion (PKCC) with a relatively low prevalence of arterial hypertension among the population of 299.16 per 10.000 population (were used as a water-food ration) ( Statistics of public health and healthcare of the CR in 1996-2006. - Cheb. MH CR. 2006, 180 pp.). As a water-food ration for creating a model for the remaining 15 animals - water and feed from the village of Kudeikha of the Poretsky district of the Chuvash Republic, which is part of the Prisursky biogeochemical subregion (PSS) with higher prevalence of arterial hypertension among the population of 443.10 per 10.000 population with p <0.05 (Table 1) (Statistics of public health and healthcare of the CR in 1996-2006. - Cheb. MH CR. 2006, 180 pp.). The indicated subregions did not differ among themselves in weather conditions, urbanization levels, atmospheric emissions, national composition and quality of medical care (Suslikov V.L. Ecological and biogeochemical zoning of territories - a methodological basis for assessing the environment and human health. - Cheb. ChGU. 2001 . - 40 p.).

The rats of the first group (control) were kept on water and feed brought from the village of Turmysh, and the rats of the second group intended to create the model were kept on water and feed from the village of Kudeikha. Vegetables (potatoes, beets, carrots), as well as wheat grains were used as feed. Drinking water was taken from decentralized sources of water supply in the respective settlements. Animals were kept in the vivarium of a medical institute under the constant supervision of a veterinarian.

To simulate arterial hypertension, such a water-feed regime was created that completely copied the natural conditions of nutrition and water supply of the population living in the territory of the compared subregions.

In connection with various ecological and biogeochemical conditions of the two regions, the water and feed used significantly differed both in the quantitative content of trace elements and in their qualitative ratio to iodine. So, in the water of the village of Kudeikha there is an excess of silicon 3.5 times, copper 5.0 times, calcium, sulfates, chlorides, as well as an unfavorable (abnormal) ratio of trace elements to iodine (Table 2).

The development of the model was accompanied by deep endocrine and biochemical disorders in the organisms of the animal group used to create the model, on the one hand, and adaptive-compensatory mechanisms in their body, on the other, as evidenced by the following.

On average, in the content of trace elements in the urine of the rat group, intended to create a model, there was an increase in iodine, cobalt, fluorine and calcium by 2-2.5 times, magnesium and zinc by 50-60%, a decrease in copper by 4 times, cobalt, selenium , cadmium and chromium 2 times, silicon by 35%. A violation of the ratio of trace elements to iodine also occurred (Table 3). Assessing the data obtained, it should be noted that with the same diuresis in rats of the simulated and control groups, the excretion of zinc, manganese, calcium, magnesium and fluorine in the experimental group of animals was increased within 12.5 ml / day.

Also, the experimental model of arterial hypertension was characterized by changes in the content of trace elements in the blood serum of the experimental group of animals. There was a significant increase in the content of iodine, fluorine (ρ <0.05) and arsenic (ρ <0.001) compared with the control group (Table 4). These shifts of microelement homeostasis were combined in time with an increase in blood pressure in animals (see the drawing, where: I, II, III, IV - quarters of the year; _____ - experimental group of rats; ---- - control group of rats). In the group of rats designed to create the model, there was a dynamic increase in blood pressure, which by the end of the experiment exceeded the background and control values by 12.0 mm Hg. These data indicate the multidirectional effect of water-feed diets on the dynamics of changes in blood pressure in experimental animals, and their abnormal relationships have a pronounced hypertensive effect.

The presence of bioaccumulation and redistribution of certain trace elements between the blood and internal organs (liver, kidneys, heart, aorta) testifies to the ongoing adaptive shifts of microelement homeostasis in the animal organism under the influence of a water-feed diet. So, in the liver tissues of the group of animals intended to create a model (Table 5), in comparison with the control, an increase in the concentration of zinc, silicon, chromium and magnesium (ρ <0.05) is observed, while a significant decrease in copper, calcium and lead (ρ < 0.05). In the tissues of the kidneys (Table 6), there is a decrease in calcium (ρ <0.01), manganese and molybdenum (ρ <0.05), while a significant increase in the concentration of zinc (ρ <0.001) is observed. In the aortic tissues of the experimental group of rats (Table 7), compared with the control, the content of arsenic, cadmium, copper, zinc, selenium (ρ <0.05), as well as chromium (ρ <0.01) is significantly higher. The concentration of trace elements such as cobalt (ρ <0.01), manganese, calcium, magnesium and lead (ρ <0.05), was significantly lower compared to the control group. Significant differences in heart tissues (Table 8) were determined for molybdenum (ρ <0.01), magnesium and lead (ρ <0.05), the content of these trace elements was higher than in the control group.

The data obtained during the study of the microelement composition of intestinal tissues (Table 9, 10, where the data *** ρ <0.001, ** ρ <0.01, * ρ <0.05), indicate a continuing violation of the microelement homeostasis in the body experimental group of animals.

It is known that the development of hypertension is due to many interacting factors: neurohumoral, hemodynamic, genetic, metabolic, etc. We analyzed the influence of the microelement composition of drinking water and feed on changes in the lipid metabolism of experimental groups of animals (Table 11).

In the body of animals intended to create the model, there was an increase in total cholesterol (cholesterol) by 0.34 mmol / L (ρ <0.05), the cholesterol content of low density lipoproteins (LDL cholesterol) increased almost 4 times (ρ <0, 01). There was a downward trend in high-density lipoprotein cholesterol (HDL cholesterol). The atherogenicity index (IA) increased by 48% (ρ <0.001).

Thus, the conducted studies confirmed that a model of biogeochemical arterial hypertension was obtained. Convincing evidence has been obtained of the participation of macro- and micronutrients of water and feed in the adaptive shifts of microelement homeostasis in animals, in the development of deep dysbiotic changes and donosological changes in lipid metabolism, combined in time with an increase in blood pressure in animals. These data provide a new look at the causal relationship of arterial hypertension with environmental and biogeochemical environmental factors.

Table 1 AH indicators per 10,000 population PKCC M ± m MSS M ± m Significance of differences P Prevalence 299.16 ± 24.23 443.1 ± 55.73 <0.05 Incidence 30.5 ± 3.53 35.31 ± 3.76 > 0.05

table 2 Indicators, mg / l v. Turmyshi (PKCC) Kudeikha village (PSS) Significance of difference (ρ) total hardness, mEq. / L 5.66 ± 0.003 3.90 ± 0.007 <0.001 chlorides 24.23 ± 7.73 80.97 ± 5.03 <0.05 sulfates 25.53 ± 4.90 103.0 ± 18.52 <0.05 I 0.67 ± 0.05 0.63 ± 0.23 > 0.05 Zn 0.033 ± 0.0185 0.021 ± 0.0033 > 0.05 Cd 0.02 ± 0.001 0.03 ± 0.005 <0.05 Co 0,00027 ± 0.000085 0,00026 ± 0.000069 > 0.05 Mo 0.001 ± 0.0003 0.003 ± 0.0003 > 0.05 Cu 0.004 ± 0.0003 0.018 ± 0.002 <0.01 F 0.69 ± 0.030 0.93 ± 0.068 <0.05 Si 3.33 ± 0.65 14.5 ± 0.37 <0.01 Mg 27.81 ± 0.68 7.2 ± 0.07 <0.005 Ca 71.56 ± 0.31 74.60 ± 0.81 <0.05 As 0.001 ± 0.0002 0.001 ± 0.0002 > 0.05

Table 3 Trace elements, mg / l Control group (n = 4) Iodine ratio Experimental group (n = 4) Iodine ratio iodine (I) 3.25 one 8.76 one cobalt (Co) 0.150 0,046 0,085 0.009 copper (Cu) 1.81 0.56 0.46 0.05 molybdenum (Mo) 0.899 0.277 0.856 0,098 zinc (Zn) 10.82 3.33 16.34 1.87 silicon (Si) 13.69 4.21 10.45 1.19 selenium (Se) 0.439 0.135 0.217 0,025 Manganese (Mn) 0.106 0,032 0.122 0.013 calcium (Ca) 548.95 168.9 1180.9 134.8 magnesium (Mg) 568.39 174.9 871.37 99.5 lead (Pb) 0.051 0.016 0,061 0.007 chromium (Cr) 0,064 0.019 0,037 0.004 cadmium (Cd) 0.005 0.002 0.003 0,0003 fluorine (F) 1.87 0.58 3.24 0.37

Table 4 Trace elements The number of samples (n) Control group M ± m, mg / l Experimental group M ± m, mg / l Significance of differences P iodine (I) four 3.13 ± 0.18 8.7 ± 1.84 <0.05 cobalt (Co) four 0.012 ± 0.002 0.015 ± 0.004 - copper (Cu) four 1.49 ± 0.37 1.66 ± 0.49 - molybdenum (Mo) four 0.044 ± 0.014 0.044 ± 0.014 - zinc (Zn) four 1.34 ± 0.54 1.74 ± 0.41 - Manganese (Mn) one 0.012 <0.001 - calcium (Ca) one 141.01 142.26 - lead (Pb) one 0,028 0,033 - magnesium (Mg) one 24.39 19.47 - arsenic (As) four 0.024 ± 0.0007 0.044 ± 0.0003 <0.001 silicon (Si) four 0.89 ± 0.29 0.99 ± 0.34 - cadmium (Cd) four 0.002 ± 0.0008 0.002 ± 0.0008 - fluorine (F) four 1.98 ± 0.06 2.98 ± 0.31 <0.05 chromium (Cr) one 0.245 0,037 -

Table 5 Trace elements Control group M ± m, mg / kg (n = 4) Experimental group M ± m, mg / kg (n = 4) Significance of differences P cobalt (Co) 0.046 ± 0.001 0.031 ± 0.012 - copper (Cu) 5.09 ± 0.79 2.87 ± 0.31 <0.05 molybdenum (Mo) 0.30 ± 0.027 0.31 ± 0.006 - zinc (Zn) 18.44 ± 0.77 21.34 ± 0.62 <0.05 Manganese (Mn) 1,072 ± 0,38 1,053 ± 0,001 - calcium (Ca) 125.04 ± 2.34 103.5 ± 4.71 <0.05 lead (Pb) 0.113 ± 0.011 0.044 ± 0.029 <0.05 magnesium (Mg) 166.94 ± 2.39 200.83 ± 2.04 <0.05 selenium (Se) 0.342 ± 0.014 0.344 ± 0.004 - silicon (Si) 8.70 ± 1.73 18.35 ± 3.57 <0.05 cadmium (Cd) 0.032 ± 0.007 0.021 ± 0.001 - arsenic (As 0.051 ± 0.012 0,053 ± 0,005 - chromium (Cr) 0.062 ± 0.024 0.192 ± 0.012 <0.05 Note: here the “-" sign indicates the lack of significance of differences

Table 6 Trace elements Control group M ± m, mg / kg (n = 4) Experimental group M ± m, mg / kg (n = 4) Significance of differences P cobalt (Co) 0.052 ± 0.009 0.044 ± 0.003 - copper (Cu) 3.70 ± 0.53 3.77 ± 0.19 - molybdenum (Mo) 0.22 ± 0.033 0.14 ± 0.011 <0.05 zinc (Zn) 15.1 ± 0.21 26.16 ± 0.12 <0.001 Manganese (Mn) 0.73 ± 0.013 0.71 ± 0.001 <0.05 calcium (Ca) 299.36 ± 3.19 208.23 ± 4.66 <0.01 lead (Pb) 0.044 ± 0.006 0.041 ± 0.004 - magnesium (Mg) 152.68 ± 4.47 160.07 ± 4.32 - selenium (Se) 0.78 ± 0.265 0.82 ± 0.095 - silicon (Si) 12.57 ± 1.48 13.45 ± 0.075 - cadmium (Cd) 0.079 ± 0.008 0.061 ± 0.006 - arsenic (As) 0,052 ± 0,002 0.047 ± 0.013 - chromium (Cr) 0.071 ± 0.0070 0.072 ± 0.0095 - Note: here the “-" sign indicates the lack of significance of differences

Table 7 Trace elements Control group M ± m, mg / kg (n = 4) Experimental group M ± m, mg / kg (n = 4) Significance of differences P cadmium (Cd) 0.004 ± 0.001 0.008 ± 0.001 <0.05 cobalt (Co) 0.094 ± 0.002 0.068 ± 0.003 <0.01 copper (Cu) 4.60 ± 0.78 7.53 ± 0.06 <0.05 molybdenum (Mo) 0.124 ± 0.012 0.123 ± 0.025 - zinc (Zn) 15.51 ± 1.47 26.92 ± 1.98 <0.05 silicon (Si) 17.41 ± 5.65 16.05 ± 2.94 - selenium (Se) 0.446 ± 0.045 0.718 ± 0.031 <0.05 Manganese (Mn) 0.435 ± 0.051 0.255 ± 0.026 <0.05 calcium (Ca) 1411.0 ± 26.23 1294.44 ± 47.97 <0.05 magnesium (Mg) 287.94 ± 3.44 235.18 ± 16.43 <0.05 lead (Pb) 0.208 ± 0.017 0.144 ± 0.002 <0.05 chromium (Cr) 0.110 ± 0.022 0.382 ± 0.029 <0.01 arsenic (As) 0.216 ± 0.003 0.253 ± 0.013 <0.05

Table 8 Trace elements Control group M ± m, mg / kg (n = 4) Experimental group M ± m, mg / kg (n = 4) Significance of differences P cobalt (Co) 0.03 ± 0.004 0.05 ± 0.018 - copper (Cu) 3.13 ± 0.24 2.57 ± 0.44 - molybdenum (Mo) 0.027 ± 0.001 0,091 ± 0,005 <0.01 zinc (Zn) 4.27 ± 0.87 6.15 ± 0.40 - Manganese (Mn) 0.25 ± 0.043 0.24 ± 0.018 - calcium (Ca) 334.25 ± 11.54 423.28 ± 43.32 - lead (Pb) 0.029 ± 0.002 0.039 ± 0.004 <0.05 magnesium (Mg) 172.93 ± 6.32 231.74 ± 8.99 <0.05 selenium (Se) 0.39 ± 0.062 0.49 ± 0.004 - silicon (Si) 7.11 ± 0.70 9.70 ± 1.99 - cadmium (Cd) 0.002 ± 0.0005 0.002 ± 0.0005 - arsenic (As) 0.163 ± 0.032 0.135 ± 0.039 - chromium (Cr) 0.013 ± 0.001 0.013 ± 0.001 - Note: here the “-" sign indicates the lack of significance of differences

Table 9 Trace elements blind M ± m, mg / kg ascending colon M ± m, mg / kg transverse colonic M ± m, mg / kg descending M ± m, mg / kg sigmoid M ± m, mg / kg direct M ± m, mg / kg Cd 0.013 ± 0.0004 0.007 ± 0.0002 0.007 ± 0.0002 0.005 ± 0.0001 0.003 ± 0.0001 0.009 ± 0.0002 Co 0.047 ± 0.031 0,054 ± 0,007 0.056 ± 0.002 0.078 ± 0.001 0,076 ± 0,038 0.042 ± 0.020 Cu 2.71 ± 0.37 5.02 ± 0.07 15.28 ± 2.1 3.62 ± 0.15 2.67 ± 0.48 3.78 ± 0.52 Mo 0.149 ± 0.037 0.069 ± 0.007 0.046 ± 0.009 0.061 ± 0.009 0.028 ± 0.015 0.052 ± 0.005 Zn 21.35 ± 1.99 46.28 ± 2.64 61.33 ± 11.40 89.30 ± 5.77 29.71 ± 9.99 106.65 ± 34.57 Si 128.83 ± 4.88 52.14 ± 0.71 69.74 ± 16.87 20.73 ± 1.96 51.50 ± 4.28 90.28 ± 2.35 Se 0.290 ± 0.018 0.330 ± 0.046 0.50 ± 0.03 0.309 ± 0.071 0.197 ± 0.056 0.231 ± 0.010 Mn 6.90 ± 0.70 1.73 ± 0.28 2.46 ± 0.64 1.07 ± 0.15 0.99 ± 0.039 0.57 ± 0.018 Ca 398.54 ± 64.51 774.05 ± 93.45 545.36 ± 22.3 193.91 ± 57.62 198.32 ± 20.2 339.59 ± 38.12 Mg 458.03 ± 82.87 208.49 ± 29.68 350.02 ± 10.25 221.92 ± 2.40 162.21 ± 10.75 180.84 ± 15.72 Pb 0.240 ± 0.004 0.261 ± 0.014 0.248 ± 0.022 0.315 ± 0.083 0.273 ± 0.034 0.186 ± 0.079 As 0.076 ± 0.002 0.116 ± 0.001 0.112 ± 0.049 0.041 ± 0.005 0.058 ± 0.007 0.108 ± 0.027 Cr 0.082 ± 0.005 0.061 ± 0.006 0.248 ± 0.22 0.299 ± 0.078 0.267 ± 0.039 0.251 ± 0.038

Table 10 Trace elements blind M ± m, mg / kg ascending colon M ± m, mg / kg transverse colonic M ± m, mg / kg descending M ± m, mg / kg sigmoid M ± m, mg / kg direct M ± m, mg / kg Cd 0.016 ± 0.001 0.005 ± 0.002 0.009 ± 0.001 0.003 ± 0.0005 0.002 ± 0.0001 0.006 ± 0.0001 Co 0.066 ± 0.016 0.059 ± 0.006 0.072 ± 0.013 0.035 ± 0.017 * 0.049 ± 0.018 0.037 ± 0.0022 * Cu 2.41 ± 0.23 4.08 ± 0.46 * 7.27 ± 3.83 2.47 ± 0.60 2,50 ± 0,29 13.74 ± 3.19 * Mo 0.101 ± 0.014 0.056 ± 0.008 0.014 ± 0.009 * 0.028 ± 0.002 * 0.024 ± 0.005 0.034 ± 0.002 * Zn 21.94 ± 0.43 24.43 ± 5.36 * 17.92 ± 4.72 * 24.04 ± 0.85 ** 22.61 ± 1.19 32.99 ± 1.19 * Si 174.56 ± 65.47 53.80 ± 11.27 41.81 ± 11.01 17.67 ± 3.38 19.40 ± 0.11 ** 24.17 ± 1.6 *** Se 0.25 ± 0.022 0.59 ± 0.118 * 0.49 ± 0.05 0.20 ± 0.012 0.23 ± 0.064 0.19 ± 0.011 * Mn 6.92 ± 0.75 2.60 ± 1.07 1.46 ± 0.001 2.37 ± 0.05 1.27 ± 0.22 0.67 ± 0.022 Ca 293.26 ± 22.69 * 666.19 ± 95.48 584.66 ± 76.21 686.95 ± 41.6 ** 84.59 ± 25.9 * 288.85 ± 94.79 Mg 170.23 ± 13.8 227.42 ± 35.22 292.87 ± 66.04 188.81 ± 37.7 112.4 ± 35.76 164.05 ± 59.30 Pb 0.013 ± 0.002 *** 0.069 ± 0.026 0.020 ± 0.007 0.044 ± 0.005 0.026 ± 0.002 * 0.061 ± 0.002 As 0.071 ± 0.015 0.144 ± 0.012 * 0,091 ± 0,034 ** 0.086 ± 0.001 ** 0.087 ± 0.023 0.105 ± 0.027 Cr 0,057 ± 0,001 0.236 ± 0.088 0.114 ± 0.038 0.291 ± 0.091 0.293 ± 0.070 0.247 ± 0.037

Table 11 Indicators, mmol / l Control group M ± m, n = 15 Experimental group M ± m, n = 15 Significance of differences P Oxc 1.51 ± 0.08 1.85 ± 0.13 <0.05 HDL cholesterol 1.26 ± 0.9 0.87 ± 0.07 <0.01 TG 0.38 ± 0.08 0.37 ± 0.1 > 0.05 Cholesterol 0.22 ± 0.06 0.96 ± 0.16 <0.01 HS VLDL 0.08 ± 0.02 0.09 ± 0.03 > 0.05 IA 0.19 ± 0.04 1.12 ± 0.03 <0.001

Claims (1)

A method for simulating arterial hypertension, characterized by the introduction of chemicals into the body of rats that affect the content of biologically active substances in the body, in the form of macro- and microelements by using the water-food ration of rats from water and feed from the subregion of human habitation, known as arterial hypertension, which contain trace elements qualitatively and quantitatively different from trace elements contained in water and feed of the subregion of human habitation, archery relatively hypertension, the development of hypertension is judged by the appearance prepathological changes in lipid metabolism in combination with a simultaneous increase in blood pressure in animals.

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