CONTENT OF GROWTH FACTORS AND HYPOXIA-INDUCIBLE FACTOR 1Α IN THE WOUND BED OF THE SKIN OF RATS WITH METABOLIC SYNDROME

N. Hrytsevych, N.S. Nikitina, L. I. Stepanova, O.M. Savchuk, V. Vereshchaka
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Abstract

Minor injuries in healthy people usually heal well, but larger wounds or the presence of various physiological (age) or pathological conditions (metabolic syndrome, obesity, diabetes, and cancer) can impede this process. The aim of our work was to determine the factors that may influence the duration of healing (growth factors and hypoxia-induced factor 1α) in the wound bed of rats with metabolic syndrome. The experiments were conducted on 80 white non-linear laboratory rats, aged 4-5 months, which were divided after birth into 2 groups of 40 animals each (20 males and 20 females). Group I rats were subcutaneously injected with saline at a dose of 8 μg/ ml on days 2, 4, 6, 8, and 10 after birth. Group II rats were administered a sodium glutamate solution at a dose of 4.0 mg/ kg at the same time. At the age of 4 months, animals of both subgroups were modeled with incised wounds . The control animals were rats in each of the groups in which wounds were not modeled. The material for biochemical studies was the skin in the areas of the former wound bed. Rats in the control group had their skin excised at the same sites as those in the experimental groups. The skin was homogenized and the content of growth factors of endothelial and nerve cells (VEGF, NGF, respectively) and hypoxia-inducible factor (HIF-1α) was determined by immuno-enzymatic method. In unoperated male rats with metabolic syndrome, the skin content of VEGF, NGF, and HIF-1a increased compared to control animals without the syndrome. In unoperated females with metabolic syndrome, VEGF levels decreased with a simultaneous increase in NGF and HIF-1α. In the wound bed of animals with metabolic syndrome, after the closure of the wound surface, the content of VEGF and HIF-1α increased, and the content of NGF remained unchanged compared with the values in unoperated rats. The results obtained indicate the involvement of growth factors VEGF and NGF and HIF-1α in prolonging the duration of healing of incised wounds in rats with metabolic syndrome. At the same time, these growth factors and HIF-1α may be involved in the mechanisms of development of some postoperative complications.
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代谢综合征大鼠皮肤伤口床的生长因子和低氧诱导因子 1α 的含量
健康人的轻微创伤通常愈合良好,但较大的伤口或存在各种生理(年龄)或病理情况(代谢综合征、肥胖、糖尿病和癌症)会阻碍这一过程。我们的研究旨在确定可能影响代谢综合征大鼠伤口愈合时间的因素(生长因子和缺氧诱导因子 1α)。实验对象是 80 只 4-5 个月大的白色非线性实验鼠,出生后分为两组,每组 40 只(雌雄各 20 只)。I 组大鼠在出生后第 2、4、6、8 和 10 天皮下注射生理盐水,剂量为 8 微克/毫升。同时,给 II 组大鼠注射谷氨酸钠溶液,剂量为 4.0 毫克/千克。在大鼠 4 个月大时,对两组大鼠的伤口进行切口建模。对照组动物为各组中没有伤口模型的大鼠。生化研究的材料是前伤口床区域的皮肤。对照组大鼠的皮肤切除部位与实验组相同。将皮肤匀浆,用免疫酶法测定内皮细胞和神经细胞生长因子(分别为 VEGF 和 NGF)以及缺氧诱导因子(HIF-1α)的含量。与未患代谢综合征的对照组相比,患代谢综合征的未手术雄性大鼠皮肤中的 VEGF、NGF 和 HIF-1a 含量均有所增加。在患有代谢综合征的未接受手术的雌性大鼠中,血管内皮生长因子的含量降低,而 NGF 和 HIF-1α 的含量同时升高。在患有代谢综合征的动物的伤口床中,伤口表面闭合后,VEGF 和 HIF-1α 的含量增加,而 NGF 的含量与未手术大鼠的数值相比保持不变。研究结果表明,生长因子 VEGF 和 NGF 以及 HIF-1α 参与了延长代谢综合征大鼠切口愈合时间的过程。同时,这些生长因子和 HIF-1α 可能参与了一些术后并发症的发生机制。
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