The method of colony-stimulating hematopoietic precursor cells in the spleen when irradiated animals

 

The invention relates to experimental medicine, may find application in radiobiological experiments, and in the future in clinical practice. The colony-stimulating hematopoietic precursor cells in the spleen during irradiation of animals is carried out by introduction deoxyribonucleic acid isolated from fish ROE. The drug is administered before or after exposure daily dose of 40-60 μg/mouse for 5-7 days. While the last dose of the drug before exposure or after the first dose of radiation administered over 1-2 hours, respectively, before or after irradiation. The method enhances the effect of colony-forming cells in the spleen at eliminating side effects. table 1.

The invention relates to medicine, namely to the stimulants of colony-forming cells, and may find application in clinical practice and radiobiological experiments.

There is a method of colony-stimulating hematopoietic precursor cells in the spleen after irradiation by injecting animals with epinephrine in the amount of 0.1-0.07 mg/mouse (Radiobiology, 1984, T. 24, No. 4, S. 545-548). The disadvantages of this method are low to the divided contraindications.

There is a method of colony-stimulating hematopoietic precursor cells in the spleen by introducing animals within 2 to 4 hours after exposure of Tris(hydroxymethyl)-aminomethan in the amount of 0.3-0.5 ml/mouse (SU, A. C. No. 1476644, MKI 5 And 61 To 31/045).

The disadvantage of this method is the use of chemically pure drug, further impact on mammals has not been studied.

The objective of the invention is the expansion of supportive funds received from environmentally friendly raw materials, which are able to increase the efficiency of colony-hematopoietic precursor cells in the spleen after irradiation of animals.

The problem is solved by introducing animals stimulating substances, at the same time as stimulating substance use deoxyribonucleic acid (DNA) in an amount of 40-60 μg/mouse. Stimulating substance is administered before or after exposure of the animals daily for 5-7 days, and the last or the first dose of stimulating substances injected at 1.0-2.0 hours before or after irradiation.

Deoxyribonucleic acid is a natural nucleoproteid of milk fish THAT 9354-024-21428156-98.

New in the present invention, Avlabari animals that were irradiated using deoxyribonucleic acid (DNA), isolated from salmon ROE, in the amount of 40-60 µg, while stimulating substance is administered to animals daily for 5-7 days before or after irradiation. The last or the first dose of stimulating substances injected at 1.0-2.0 hours before or after irradiation of animals.

The use of deoxyribonucleic acid (DNA) as a stimulator of hematopoietic colony-precursor cells in the spleen before or after irradiation of animals not previously been known.

Thus, the claimed invention meets the criteria of the invention of “Novelty” and “Inventive step” because it is not obvious to a person skilled in the art.

The method consists in the following.

To assess stimulating preventive and curative effects of deoxyribonucleic acid (DNA) on hematopoietic precursor cells in the spleen in animals that were irradiated experimental investigations were carried out on outbred mice weighing 18-20 g, in each group of at least 10 animals. The experiment was repeated three times.

As the definition of preventive actions deoxyribonucleic acid animals daily for 5-7 days for 1.0-2.0 hours before irradiation was injected under the skin Wei was irradiated on the device Rocus-M at a dose of 7 Gy, at dose rate of 0.9 G/min

As the definition of therapeutic action deoxyribonucleic acid first animals were irradiated on the device Rocus-M at a dose of 7 Gy at the dose rate of 0.9 Gy/min, then the animals daily for 5-7 days was injected under the skin in the thigh deoxyribonucleic acid (DNA) in an amount of 40-60 µg, its pre-dissolved in 0.85% saline solution, and the first dose of DNA was injected through a 1.0-2.0 hours after exposure.

On the eighth day after the application of deoxyribonucleic acid, the mice were killed by decapitation, removed the spleen and within two hours were fixed in liquid Buena. After fixing counted the number of endogenous colonies with the aid of a magnifying glass.

To confirm the stimulating effect of the new funds comparative study was carried out with the introduction of animal 40-60 μg of saline.

Dosage deoxyribonucleic acid has been determined by experiment, as the results suggest that smaller doses less than 40 µg stimulating effect of the drug is not significantly different from the control, while increasing the dosage above 60 µg number of colonies is not growing, which indicates ina scheme for the use of the drug is due to pathophysiological laws of development of adaptive reactions of living organisms.

Introduction stimulator for 1.0-2.0 hours before exposure or after exposure provides the necessary stimulation neuroimmunoendocrine system that promotes radioresistance of the body.

Data on the influence of deoxyribonucleic acid by the number of endogenous colonies depending on the dose and duration of its application are presented in the table.

The table shows that the introduction of irradiated mice 40-60 µg deoxyribonucleic acid increases the number of endogenous colonies on the spleen 3.3 times, and the introduction of mice 40-60 µg deoxyribonucleic acid before irradiation increases the number of endogenous colonies on the spleen 2.5 times.

The observed increase in the number of endogenous colonies associated with an increase in the number of survivors of hematopoietic precursor cells needed to restore the blood, and also indicates that deoxyribonucleic acid largely affects the increase of endogenous colonies in irradiated mice and can be used more effectively as a therapeutic drug.

With the introduction of animal physiological solution in the amount of 40-60 µg before irradiation on the 8th day of endocrine there were 8,11,5 the options were carried out on outbred mice-males weighing 18-20 g, which were divided into 2 groups of 10 animals each.

1st group (control) animals were injected with saline.

the 2nd group was introduced deoxyribonucleic acid number of 50 mg for 6 days. Deoxyribonucleic acid dissolved in 85% saline solution and injected under the skin in the thigh once a day, and the last before irradiation dose administered to animals for 1.5 hours before irradiation.

Then mice were irradiated at a dose of 7.0 Gy at the dose rate of 0.9 G/min on the phone Rocus) Dose selected in advance empirically and depends on sex, breed and season.

On the 7th day, the mice were killed by decapitation, removed the spleen and recorded it in liquid Buena (saturated solution of picric acid in water - acetic acid - 40% formalin -15:15:1). After fixation within days of the spleen was transferred into 70% ethanol and counted colonies. The calculation was made with the help of a magnifying glass.

The average number of endogenous colonies in the application of DNOC was 20.53,1 in the application of saline - 8,11,5.

The table shows that the introduction deoxyribonucleic acid increases the number of endogenous colonies on the spleen nexposure) gives the highest stimulating effect.

Example 2 was carried out analogously to example 1, however, the DNOC was administered to mice in amounts of 40 mg for 5 days and the last dose for 1.0 hours before irradiation.

On the 6th day, the mice were killed by decapitation, removed the spleen and recorded it in liquid Buena (saturated solution of picric acid in water - acetic acid - 40% formalin -15:15:1). After fixation within days of the spleen was transferred into 70% ethanol and counted colonies. The calculation was made with the help of a magnifying glass.

The average number of endogenous colonies were 12.01,3, when using saline - 8,11,5.

The table shows that the introduction deoxyribonucleic acid increases the number of endogenous colonies in the spleen compared with control 1.5 times, and the use of DNOC as prophylaxis (for 1.0 h before irradiation) gives a highly stimulating effect.

Example 3 was carried out analogously to example 1, however, the DNOC was administered to mice in the amount of 60 mcg for 7 days and the last dose for 2.0 hours before irradiation.

On the 8th day, the mice were killed by decapitation, removed the spleen and recorded it in liquid Buena (saturated solution of picric acid in water - acetic acid to which was cityval colony. The calculation was made with the help of a magnifying glass.

The average number of endogenous colonies amounted to $ 19.13,3, when using saline - 8,11,5.

The table shows that the introduction deoxyribonucleic acid increases the number of endogenous colonies in the spleen compared with control 2.3 times, and the use of DNOC as a preventive measure (for 2.0 hours before irradiation) gives a highly stimulating effect, however, further increase of endogenous colonies does not occur.

Example 4.

The experiments were carried out on outbred mice-males weighing 18-20 g, which were divided into 2 groups of 10 animals each. Then mice were irradiated at a dose of 7.0 Gy at the dose rate of 0.9 G/min on the phone Rocus) Dose selected in advance empirically and depends on sex, breed and season.

1st group (control) animals were injected with saline.

the 2nd group was introduced deoxyribonucleic acid number of 50 mg for 6 days. Deoxyribonucleic acid dissolved in 85% saline solution and injected under the skin in the thigh once a day, and after the first exposure dose is administered to animals after 1.5 hours after obl (saturated solution of picric acid in water acetic acid - 40% formalin -15:15:1). After fixation within days of the spleen was transferred into 70% ethanol and counted colonies. The calculation was made with the help of a magnifying glass.

The average number of endogenous colonies was 15.32,2, and the application of saline - 4,61,6.

The table shows that the introduction deoxyribonucleic acid increases the number of endogenous colonies in the spleen compared with control 3.3 times, and the use of DNOC as a remedy for 1.5 hours after irradiation gives the highest stimulating effect.

The observed increase in the number of endogenous colonies associated with an increase in the number of survivors of hematopoietic precursor cells needed to restore blood.

Example 5 was carried out analogously to example 4, however, the DNOC was administered to mice in amounts of 40 mg for 5 days, and the first dose of drug was administered after 1.0 hour after exposure.

On the 6th day, the mice were killed by decapitation, removed the spleen and recorded it in liquid Buena (saturated solution of picric acid in water - acetic acid - 40% formalin -15:15:1). After fixation during the day splenic prenosive endogenous colonies was 12.51,3, and the application of saline - 4,61,6.

The table shows that the introduction deoxyribonucleic acid increases the number of endogenous colonies in the spleen compared with control 2.1 times, and the use of DNOC as treatment (after 1.0 hours after irradiation) gives a highly stimulating effect.

Example 6 was carried out analogously to example 4, however, the DNOC was administered to mice in the amount of 60 mcg for 7 days, and the first dose of drug was administered after 2.0 hours after exposure.

On the 8th day, the mice were killed by decapitation, removed the spleen and recorded it in liquid Buena (saturated solution of picric acid in water - acetic acid - 40% formalin -15:15:1). After fixation within days of the spleen was transferred into 70% ethanol and counted colonies. The calculation was made with the help of a magnifying glass.

The average number endogennyh colonies amounted to $ 14.71.5, and in the application of saline - 4,61,6.

The table shows that the introduction deoxyribonucleic acid increases the number of endogenous colonies in the spleen compared with control in 2.8 times, and the use of DNOC as treatment (through 2,0 the place.

Claims

The method of colony-stimulating hematopoietic precursor cells in the spleen in animals that were irradiated by introducing animals stimulating substances, characterized in that as a last used DNA extracted from fish ROE, which is injected before or after irradiation daily dose of 40-60 μg/mouse for 5-7 days, with the last dose before exposure or after the first dose of radiation is administered for 1-2 hours, respectively, before or after irradiation.

 

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