RU2477530C2 - Method for endothelial dysfunction correction by solution of homoeopathic dilutions of interleukin-6 antibodies - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: endothelial dysfunction is induced in experimental Wistar male rats for 28 days by daily intraperitoneal introduction of N-nitro-L-arginine methyl ester 12.5 mg/kg a day. An agent for dysfunction correction is a mixture of solutions of homoeopathic dilutions of interleukin-6 antibodies - C12, C30, C200; it is introduced at the same time for 28 day intragastrically 2 times a day in a dose of 4.5 ml/kg.

EFFECT: method provides effective endothelial dysfunction correction.

1 tbl

Description

The invention relates to medicine, in particular to experimental cardiopharmacology, and can be used to correct N-nitro-L-arginine methyl ether (L-NAME) -induced endothelial dysfunction.

The prior art method for the correction of endothelial dysfunction with a mixture of solutions of homeopathic dilutions of polyclonal rabbit antibodies to endothelial synthase of human nitric oxide - C12, C30, C200 (RF №2306953 C1, A61K 39/395, 09/27/2007), the main mechanism of action of which is an increase in the number of eNOS, which limits the effectiveness of this method.

The objective of the invention is to provide a method of endothelial dysfunction, leading to an effective prevention of inflammation of the vessel wall and the development of endothelial dysfunction.

The solution to this problem is ensured by the fact that against the background of L-NAME simulation of induced endothelial dysfunction in the experiment, intraperitoneal administration to the laboratory animal for 28 days of NO synthesis blocker N-nitro-L-arginine methyl ether (L-NAME) at a dose of 12.5 mg / kg / day its correction is carried out by introducing a mixture of solutions of homeopathic dilutions of antibodies to interleukin-6 - C12, C30, C200, intragastrically, 2 times a day at 4.5 ml / kg (9 ml / kg / day.).

The use in the claimed method of a mixture of solutions of homeopathic dilutions of antibodies to interleukin-6 - C12, C30, C200 leads to a decrease in the adhesion of the endothelium, resulting in reduced binding of inflammatory cells on its surface, which prevents the formation of inflammation of the vessel wall and thrombosis. In addition, the claimed method is aimed at expanding the arsenal of tools for the correction of endothelial dysfunction.

The claimed method can be carried out as follows.

The experiments were carried out on white rats male Wistar line weighing 250-300 g. N-nitro-L-arginine methyl ether (L-NAME) was administered intraperitoneally at a dose of 12.5 mg / kg / day. On the 29th day from the start of the experiment, under anesthesia (thiopental sodium 50 mg / kg), a catheter is inserted into the left carotid artery to record blood pressure (BP), bolus administration of pharmacological agents is carried out in the right femoral vein. Hemodynamic parameters: systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) are measured continuously using the TSD104A sensor and MP100 hardware and software complex, manufactured by Biopac System, Inc., USA. Functional tests: endothelium-dependent vasodilation (ESV) - intravenous administration of acetylcholine (AH) at a dose of 40 μg / kg, endothelium-independent vasodilation (ENZV) - intravenous administration of sodium nitroprusside (NP) at a dose of 30 μg / kg.

The degree of development of endothelial dysfunction is estimated using the coefficient of endothelial dysfunction (QED), which is the ratio of the area of the triangle above the trend of the reaction of blood pressure recovery in response to the introduction of NP to the area of the triangle above the trend of the reaction of blood pressure recovery in response to the introduction of AH.

When statistical data processing was calculated, the average value, the standard deviation. Differences were considered significant at p <0.05.

Processing of the obtained experimental data during functional tests for endothelium-dependent (acetylcholine 40 μg / kg iv) and endothelium-independent (nitroprusside 30 mg / kg iv) vascular relaxation in experimental animals revealed that intraperitoneal administration of N-nitro-L -arginine methyl ester (L-NAME) at a dose of 12.5 mg / kg, for 28 days causes an increase in the coefficient of endothelial dysfunction to 3.5 ± 0.5 srvc. (table 1), whereas in the control group (intragastric administration of distilled water, at a dose of 9 ml / kg / day), it amounted to 1.2 ± 0.1 conventional units.

In the group of animals, where against the background of the introduction of N-nitro-L-arginine methyl ester (L-NAME) at a dose of 12.5 mg / kg for 28 days, a mixture of solutions of homeopathic dilutions of polyclonal antibodies to interleukin-6 - C12, C30 was intragastrically , С200, QED amounted to 2.2 ± 0.2 conventional units, which is significantly lower than in the group with pathology modeling.

Thus, the obtained results allow us to ascertain the correction of L-NAME-induced endothelial dysfunction with the introduction of N-nitro-L-arginine methyl ether (L-NAME) at a dose of 12.5 mg / kg, for 28 days with a mixture of solutions of homeopathic dilutions of antibodies to interleukin-6 - C12, C30, C200, with intragastric administration at a dose of 9 ml / kg, reducing the QED to the level of that in the control group of animals - 1.2 ± 0.1 conventional units

Table 1 Dynamics of blood pressure and endothelial dysfunction coefficient in modeling N-nitro-L-arginine methyl ester (L-NAME) -induced endothelial dysfunction and its correction with a mixture of solutions of homeopathic dilution of antibodies to interleukin-6 - C12, C30, C200 at a dose of 9 ml / kg / day Groups of animals Functional
naya test GARDEN, mmHg DBP, mmHg S of the vascular reaction during ESVD with AH and ENVD with NP, conventional units QED, conventional units Control (daily, intragastric administration of distilled water 9 ml / kg / day.) Source 159.2 ± 5.4 124.2 ± 4.7 1.2 ± 0.1 OH 96.9 ± 6.7 52.0 ± 3.0 3071.2 ± 501.1 NP 113.8 ± 6.1 55 ± 2.4 3617.2 ± 560.1 Receiving L-NAME (12.5 mg / kg) Source 204.8 ± 10 * 164.2 ± 5.9 * 3.5 ± 0.5 * OH 111.3 ± 7.4 64.7 ± 4.3 * 3700.2 ± 536.9 NP 118.2 ± 9.9 61.4 ± 4.4 11922.8 ± 1838.9 * L-NAME (12.5 mg / kg) + a mixture of solutions of homeopathic dilutions of antibodies to interleukin-6, - C12, C30, C200 (9 ml / kg / day.) Source 209.9 ± 7.6 * 170 ± 3.6 * 2.2 ± 0.2 ** OH 116.9 ± 6.0 * 69.9 ± 3.1 * 3510 ± 435.4 NP 97.1 ± 6.7 59.4 ± 3.8 7346.7 ± 469.6 * Note: * - p <0.05 in comparison with the control group; ** - p <0.05 compared with the L-NAME group. GARDEN - systolic blood pressure, DBP - diastolic blood pressure, S - area above the curve for the restoration of blood pressure during pharmacological tests, QED - coefficient of endothelial dysfunction

Claims (1)

A method for correcting endothelial dysfunction with a solution of homeopathic dilutions of antibodies to interleukin-6, characterized in that in the experiment, rats of Wistar males are induced to induce endothelial dysfunction by daily intraperitoneal administration of N-nitro-L-arginine methyl ester (L-NAME) at a dose of 12 for 28 days , 5 mg / kg per day, while a mixture of solutions of homeopathic dilutions of antibodies to interleukin-6 - C12, C30, C200, which is administered at the same time for 28 days intragastrically, is used as a means for correcting dysfunction basics per day at 4.5 ml / kg.