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THE EFFECT OF NEW FORMS FOR EXTERNAL APPLICATION ON THE VASODILATING FUNCTION OF THE ENDOTHELIUM AND THE CONCENTRATION OF ENDOTHELIAL NITRIC OXIDE SYNTHASES IN RATS WITH AN EXPERIMENTAL MODEL OF A PATHOLOGICAL SCAR AT EARLY HEALING TIMES

Introduction: According to statistical data, the tendency towards an increase in the number of patients with keloid and hypertrophic scars at the site of skin lesions remains in the world, which in most cases is due to the lack of effective methods for preventing this type of complications. Therefore, the development of new methods of pharmacological correction, which allow us to normalize the wound healing process at an early stage, seems very relevant. One of the promising areas for the search for substances suitable for the prevention of pathological scars is the study of natural compounds possessing endothelioprotective activity, since, according to modern ideas, it is the endothelial dysfunction that underlies the pathogenesis of this complication.

Materials and methods: All studies were performed on 60 male rats of the Wistar line, divided into 6 experimental groups. New forms for external use based on flavonoids PMFI-92 and PMFI-93 and comparison preparations "Kontraktubeks", "Egallohit" were used as research objects. The effect of new PMFI-92 and PMFI-93 formulations on the vasodilating function of the endothelium of the skin of animals with chemical burn was introduced with the introduction of nitric oxide synthesis modifiers: acetylcholine (ACS), L-arginine, nitro-L-arginine methyl ester (L-NAME). The effect of local pharmacological support in this pathology on the level of endothelial (eNOS), neuronal (nNOS) and inducible (iNOS) nitric oxide syntheses was determined by the method of solid phase enzyme immunoassay (ELISA).

Results and discussion: Application of the proposed new forms based on natural compounds PMFI-92 and PMFI-93 allows to improve the vasodilating function of the endothelium already at the early stages of wound healing, with an increase in the concentration of eNOS and nNOS, as well as a decrease in the concentration of iNOS.

Conclusion: The experimental data obtained by us testify to the pronounced positive effect of the local application of PMFI-93 and PMFI-92 compositions on the vasodilating function of the skin vessels, and also to restore the balance between the activities of various forms of nitric oxide synthases.

Иллюстрации

 

Fig. 1. Initial velocity of blood flow in the damaged area of the skin, cm/s

Note: α - is statistically significant in relation to the group of pseudo-operated animals (p <0.001), single-factor analysis with the Bonferroni amendment

 

 

Fig. 2. Increase in blood flow velocity with intravenous injection of acetylcholine

Note: * - statistically significant with respect to the initial SC (p <0.05), ** - statistically significant with respect to the initial SC (p <0.01), γ - statistically significant in relation to the group of pseudo-operated animals (p < 0.05), Δ - statistically significant in relation to the group of negative control animals (p <0.05), single-factor analysis with the Bonferroni amendment idenced by an increase in blood flow velocity by 17.39% of the baseline (p <0.05), which is 2, 14 times higher than in NK animals. In addition, the blood flow velocity of this group of rats was significantly different from the group of the comparison drug "Kontraktubeks", where the blood flow velocity increased by 16.87% compared to its baseline level, and was 1.18 times higher than in the group receiving " Egallohit»(+ 14.76% of the initial level). In response to the introduction of the ACS, the blood flow velocity in the group of animals receiving PMFI-92 increased by 17.62% (p <0.05) from its baseline, the index was significantly different from the ND and the groups of animals that received the comparator. Changes in the rate of cutaneous blood flow with intravenous administration of the ACS in all experimental groups are shown in Figure 2.

 

Fig. 3. Increase in blood flow velocity with intravenous administration of L-arginine

Note: * - statistically significant with respect to the initial SC (p <0.05), ** - statistically significant with respect to the initial SC (p <0.01), γ - statistically significant in relation to the group of pseudo-operated animals (p < 0.05), Δ - statistically significant in relation to the group of negative control animals (p <0.05), single-factor analysis with the Bonferroni amendment

 

Fig. 4. The drop in blood flow velocity with intravenous injection of L-NAME

Note: * - statistically significant with respect to the initial SC (p <0.05), ** - statistically significant with respect to the initial SC (p <0.01), γ - statistically significant in relation to the group of pseudo-operated animals (p < 0.05), Δ - statistically significant in relation to the group of negative control animals (p <0.05), single-factor analysis with the Bonferroni amendment

 

Table 1. Change in the rate of cutaneous blood flow with the introduction of analyzers 14 days after the reproduction of the pathology

 

Note: * - statistically significant with respect to the initial blood flow velocity (p <0.05), single-factor analysis with Bonferroni correction; ** - statistically significant with respect to the initial blood flow velocity (p <0.01), single-factor analysis with Bonferroni correction; *** - statistically significant with respect to the initial blood flow velocity (p <0.001), single-factor analysis with Bonferroni correction; γ - statistically significant in relation to the group of pseudo-operated animals (p <0.05), single-factor variance analysis with Bonferroni amendment; Δ - statistically significant in relation to the group of negative control animals (p <0.05), single-factor analysis with the Bonferroni amendment; p is the level of the reliable difference.

 

Table 2. Determination of the concentrations of different isoforms of nitric oxide synthases at 7 and 14 days of the experiment

Note: # - statistically significant in relation to the group of pseudo-operated animals (p <0.05), U - Mann-Whitney test; ▲ - statistically significant in relation to the negative control group (p <0.05), U - Mann-Whitney test.

DOI: 10.18413/2313-8971-2017-3-4-151-159
Количество просмотров: 241 (смотреть статистику)
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