RU2547786C1 - Method for increasing skin graft survival in reduced circulation environment with use of dihydroquercetin - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: skin graft is simulated in laboratory animals on the second experimental day. Dihydroquercetin is administered intragastrically in a daily dose of 5.5 mg/kg from the first day every 46 hours of the experiment.

EFFECT: increasing the skin graft survival in the reduced circulation environment by activating the pre-conditioning process.

1 ex, 1 tbl

Description

The invention relates to medicine, in particular to experimental surgery and experimental pharmacology, and can be used to correct ischemia.

A known method of increasing the survival of a skin flap on a leg by distant ischemic preconditioning (RU 2429547 C1). Its disadvantage is that the method is not without the potential danger of ischemic episodes for pathologically altered tissues and is applicable mainly to a healthy body.

Closest to the claimed solution is the "Method of pharmacological correction of survival rates of ischemic tissues in the conditions of reduced blood circulation" (RU 2438190 C1). Correction of ischemia is carried out by recombinant erythropoietin. The advantage of this method is that the activation of the preconditioning process is carried out by a pharmacological preparation. That is, there is no episode of ischemia, which can have a damaging effect on the tissue. However, the disadvantage of this method is that erythropoietin is chosen as the initiator of the preconditioning process. Numerous researchers tend to consider him the humoral agent of preconditioning. However, this is a hormonal protein preparation, and there are a number of contraindications for its use, namely arterial hypertension, cancer. In addition, methods are known to activate the preconditioning process by direct stimulation of the main effector link of ATP-dependent potassium channels. Undoubtedly relevant is the study of drugs that can activate various stages of the preconditioning process.

The technical result of the invention is the development of an effective way to increase the survival of a skin flap in conditions of reduced blood circulation, including the use of a pharmacological drug, non-toxic, with a minimum number of contraindications.

The technical result is achieved by the fact that when modeling a skin flap under reduced blood circulation on the second day of the experiment, from the first day every 46 hours of the experiment, dihydroquercetin is administered intragastrically to the laboratory animal in a daily dose of 5.5 mg / kg.

The main advantage of the proposed method is the absence of side effects (except for individual intolerance) of the pharmacological agent, since it belongs to the class of flavonoids. It is known that with preliminary oral administration, the drug under conditions of severe hypobaric hypoxia exerted both an antioxidant and antihypoxic effect on the body. Such properties of the drug are probably due to the fact that DHA, due to the hydrophobic nature of the structure, is able to penetrate the hydrophobic region of the membranes and thereby significantly reduce the mobility of lipids. Thus, this drug stabilizes membranes under conditions of oxidative stress and acts as a structural antioxidant. In addition, it is known that flavonoids are capable of shunting the work of NADH-dehydrogenase by taking electrons from NADH and transferring them to the next - the third mitochondrial chain complex, normalizing the processes of oxidative phosphorylation (Lukyanova L.D., 2011). Based on the results obtained, it can be assumed that dihydroquercetin is able to both protect cells from free radicals and increase the efficiency of oxygen use by increasing the efficiency of tissue respiration. Each tissue and organ has a different sensitivity to pharmacological drugs. In surgical practice, the study of drugs that increase the survival of a skin flap under ischemic conditions is relevant.

The method is as follows.

The experiments were carried out on white Wistar rats weighing 220-250 g. Modeling of the skin flap was carried out under anesthesia (chloral hydrate 300 mg / kg ip) on the second day of the experiment. Having departed 1 cm from the xiphoid process along the white line of the abdomen, having previously sized the size of the stencil, cut out a skin flap: 1 cm - base, 4 cm - length, keeping the feeding vessel, isolated in a plastic bag, the edges of the skin are sutured with a continuous suture. The survival of a skin flap is evaluated on the sixth day of the experiment, by measuring the area of the surviving flap tissue in the group of animals with modeling of the skin flap and in the group with modeling of the skin flap and resveratrol.

Dihydroquercytin is administered intragastrically at a daily dose of 5.5 mg / kg from the first day every 46 hours of the experiment.

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

EXAMPLE OF SPECIFIC PERFORMANCE

The experiments were carried out on white rats male Wistar strain weighing 220-250 g. The experimental animals were divided into the following groups:

1. control (n = 10);

2. using dihydroquercytin (n = 10).

Animals of both groups had a skin flap modeled on the second day of the experiment. Under anesthesia (chloral hydrate 300 mg / kg intraperitoneally), departing 1 cm from the xiphoid process along the white line of the abdomen, having previously sized the stencil, cut out a skin flap: 1 cm - base, 4 cm - length, keeping the feeding vessel, isolated in polyethylene bag, the edges of the skin were sutured with a continuous suture. Dihydroquercitin was administered intragastrically to the animals of the second group at a daily dose of 5.5 mg / kg from the first day every 46 hours of the experiment.

Assessment of the survival of the skin flap was performed on the sixth day of the experiment, measuring the area of healthy tissue.

The results of the evaluation of the survival of the skin flap are presented in table 1.

The introduction of experimental animals dihydroquercetin contributed to a significant (p <0.05) increase in the area of surviving flap tissue.

Table 1 The survival rate of the skin flap in the conditions of reduced blood circulation on the 6th day of the experiment (5th day after modeling) (M ± m) Group (n = 10) Healthy flap tissue area in Cm ² % Modeling of the skin flap (control) 1.6 ± 0.02 40 Modeling a skin flap + dihydroquercin 2.7 ± 0.17 * 68.5 Note: * - p <0.05 when compared with the control group; dihydroquercytin intragastrically, in a daily dose of 5.5 mg / kg from the first day every 46 hours of the experiment

Thus, the obtained results allow one to ascertain an increase in the survival of a skin flap under conditions of reduced blood circulation, simulated on the second day of the experiment, with the daily dose of 5.5 mg / kg dihydroquercitin administered to the experimental animal from the first day every 46 hours of the experiment.

Claims (1)

A method for increasing the survival of a skin flap in conditions of reduced blood circulation, including modeling a skin flap in an experimental animal and administering a pharmacological agent, characterized in that the simulation is carried out on the second day of the experiment, and dihydroquercin is used as a pharmacological agent, which is administered to the animal intragastrically at a daily dose of 5, 5 mg / kg from the first day every 46 hours of the experiment.