RU2507596C1 - Method for pharmacological correction of skeletal muscle ischemia with l-norvaline - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: skeletal muscle ischemia in rats is corrected by simulating leg muscle ischemia on the second experimental day. The ischemia is corrected by the intragastric administration of L-norvaline in a daily dose of 10.0 mg/kg from the first experimental day every 46 hours for 7 experimental days.

EFFECT: effective experimental treatment of the skeletal muscle ischemia ensured by stimulation of neovasculogenesis.

1 ex, 1 tbl

Description

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

Closest to the claimed solution is a method for correcting ischemia using distant ischemic preconditioning, proposed by M.V. Pokrovsky et al. Patent for invention RU 2438192 C1.

However, this decision does not evaluate the effect of L-norvaline on the state of the microvasculature in the ischemic skeletal muscle.

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. The drug is administered every 46 hours, given that by this time the preconditioning effect is weakening, the first 7 days of the experiment, since it is at this stage that the activation of neoangiogenesis in ischemic muscle is most effective.

The technical result of the invention is the development of a method for pharmacological correction of skeletal muscle ischemia, including the use of L-norvaline.

The technical result is achieved by the fact that when modeling skeletal muscle ischemia on the second day of the experiment, L-norvaline is administered intragastrically to the laboratory animal in a daily dose of 10 mg / kg every 46 hours for the first 7 days of the experiment.

The method is carried out as follows.

The experiments are carried out on white rats of the Wistar line weighing 220-250 g.

Ischemia is modeled on the second day on the muscles of the right lower leg of the rat by surgical removal of a section of the great vessels, including the femoral, popliteal, anterior and posterior tibial arteries.

The level of microcirculation in the calf muscles is determined using Biopac systems equipment: MP100 polygraph with laser Doppler flow meter LDF100C and invasive needle probe TSD144. Registration and processing of laser Doppler flowmetry (LDF) results is performed using the AcqKnowledge software version 3.8.1., Microcirculation values are expressed in perfusion units (PE). The microcirculation level is recorded at five points (the middle of the muscle length, points 3-5 mm above and below, lateral and medial of the first).

Registration of the microcirculation level is carried out on the 28th day after the operation in the groups of falsely operated animals, with modeling of ischemia of the leg muscles and in the group of animals to which resveratrol was administered.

L-norvaline is administered intragastrically at a daily dose of 10.0 mg / kg every 46 hours for the first 7 days 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

Experimental animals were divided into the following groups:

1. falsely operated animals (n = 10);

2. modeling of ischemia of the leg muscles (n = 10);

3. modeling of ischemia of the leg muscles + L-norvaline (n = 10);

Ischemia of the muscles of the right lower leg was simulated on the second day under anesthesia (chloral hydrate intraperitoneally 300 mg / kg of weight) by operative removal of the section of the great vessels, including the femoral, popliteal, anterior and posterior tibial arteries. Correction of muscle ischemia was performed in animals of the 3rd group by intragastric administration of resveratrol in a daily dose of 2.0 mg / kg every 46 hours for the first 7 days of the experiment.

The level of microcirculation in the calf muscles was determined using Biopac systems equipment: MP100 polygraph with laser Doppler flow meter LDF100C and invasive needle probe TSD144 for 28 days. The registration and processing of laser Doppler flowmetry (LDF) results was performed using the AcqKnowledge software version 3.8.1., Microcirculation values were expressed in perfusion units (PE). The microcirculation level curve was recorded at five points (the middle of the muscle length, points 3-5 mm above and below, lateral and medial first) for 30 seconds at each point. From the five values obtained, the average was deduced, which was entered into the protocol and was taken as the level of microcirculation in the calf muscles in this animal. From the 10 obtained values, the average was calculated, which was taken as the level of microcirculation in this group of animals at this time of the study.

Table 1. The results of assessing the level of microcirculation in the leg muscles of animals of the experimental groups (M ± m) in perfusion units on the 28th day after the operation. Groups 28 days (n = 10) False-operated animals 532 ± 33 Shin Muscle Ischemia 361 ± 8 * Shin Muscle Ischemia + L-Norvaline 781 ± 28 ** Note. * - p <0.05 in comparison with a group of intact animals; ** - p <0.05 compared with a group of animals with ischemia of the tibia muscle; L-norvaline in a daily dose of 10.0 mg / kg every 46 hours for the first 7 days of the experiment.

The average microcirculation level in the intact muscle of the tibia of rats is 526 ± 34 PE. The results of assessing the level of microcirculation in animals of the experimental groups are presented in table 1.

In the group of false-operated animals, the average value of the level of microcirculation in the muscles of the right tibia does not significantly differ from the indicators in the group of intact animals (526 ± 34 PE) (p = 0.19). In the shin muscle ischemia modeling group, the microcirculation level was significantly lower than the value in the intact muscle (p <0.05).

The introduction of L-norvaline contributed to a significant increase in the level of regional blood flow in the ischemic muscle of the tibia of rats compared with the parameters in the control group (p <0.05).

Thus, the obtained results allow us to state the pharmacological correction of skeletal muscle ischemia with L-norvaline.

Claims (1)

A method for pharmacologically correcting skeletal muscle ischemia with L-norvaline, characterized in that when modeling skeletal muscle ischemia on the second day of the experiment, L-norvaline is administered intragastrically to the laboratory animal in a daily dose of 10.0 mg / kg, every 46 hours for the first 7 days of the experiment.