Immunomodulatory and neurotropic activities of synthetic peptides in a model of brain injury in rats

N. B. Serebryanaya, S. N. Shanin, T. A. Filatenkova, E. Fomicheva, A. S. Komlev, O. Shamova
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Abstract

Treatment of consequences of traumatic brain injury (TBI) remains one of the current problems of medicine. To increase the effectiveness of treatment of post-traumatic complications, various drugs are recommended, including the peptide with neuromodulatory activity Semax.The present study aims to determine the presence of neuro- and immunoprotective properties of the synthetic peptide PR5, composed of fragments of proline-rich antimicrobial peptides.The work was performed on male Wistar rats weighing 300-350 g. The “falling weight” model of mechanical brain injury was used, which mainly causes diffuse brain damage. The synthesized peptide PR5, composed of fragments of known proline-rich peptides of animal neutrophils, and the peptide preparation Semax in the form of a 1% aqueous solution were used. The drugs were administered intranasally 1 hour after TBI, then twice a day for 4 days at a dose of 100 mg/kg body weight. Control animals received physiological saline in the same regimen as the peptide preparations.TBI led to a significant decrease in body weight, but in rats receiving the peptide preparation Semax, the decrease in body weight was significantly less than in control animals, and the PR5 preparation completely prevented the decrease in body weight after TBI. After TBI, the proliferative activity of lymphocytes was suppressed and the cytotoxicity of NK cells decreased. In animals treated with peptide preparations, there was no significant suppression of NK cell cytotoxicity, and the proliferative activity of lymphocytes was restored to the level of control animals by day 14 after TBI. Both peptide preparations used contributed to higher locomotor activity, and in animals treated with the PR5 peptide, this type of activity reached the parameters of control animals. The reduction in freezing duration in groups treated with peptide preparations indicates the presence of a sedative effect.The peptide preparation PR5 was active in this series of experiments, showing immunotropic and neuroprotective activity comparable to the Semax preparation. Further studies aimed at confirming the identified types of activity of the peptide preparation PR5 may justify its prospects for clinical use as a new nootropic agent.
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合成肽在大鼠脑损伤模型中的免疫调节和嗜神经活性
创伤性脑损伤(TBI)后遗症的治疗仍然是当前医学的难题之一。为了提高治疗创伤后并发症的有效性,推荐使用多种药物,包括具有神经调节活性的肽Semax。本研究旨在确定由富含脯氨酸的抗菌肽片段组成的合成肽PR5的神经和免疫保护特性的存在。实验对象为体重300-350 g的雄性Wistar大鼠。采用机械性脑损伤的“落重”模型,主要造成弥漫性脑损伤。采用已知动物中性粒细胞富含脯氨酸肽片段合成的肽PR5和1%水溶液形式的肽制剂Semax。这些药物在脑外伤后1小时鼻内给药,然后以100 mg/kg体重的剂量每天两次,连续4天。对照动物以与肽制剂相同的方案给予生理盐水。脑外伤后体重明显下降,但接受肽制剂Semax的大鼠体重下降幅度明显小于对照组,PR5制剂完全阻止了脑外伤后体重下降。脑外伤后淋巴细胞增殖活性受到抑制,NK细胞的细胞毒性下降。经肽制剂处理后,NK细胞毒性无明显抑制,淋巴细胞增殖活性在TBI后第14天恢复到对照动物水平。使用的两种肽制剂都有助于提高运动活性,并且在PR5肽治疗的动物中,这种类型的活动达到了对照动物的参数。在用肽制剂治疗的组中,冷冻时间的减少表明存在镇静作用。肽制剂PR5在本系列实验中表现出活性,表现出与Semax制剂相当的免疫和神经保护活性。进一步的研究旨在确认肽制剂PR5的活性类型,可能证明其作为一种新的促智药的临床应用前景。
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来源期刊
Medical Immunology (Russia)
Medical Immunology (Russia) Medicine-Immunology and Allergy
CiteScore
0.70
自引率
0.00%
发文量
88
审稿时长
12 weeks
期刊介绍: The journal mission is to promote scientific achievements in fundamental and applied immunology to various medical fields, the publication of reviews, lectures, essays by leading domestic and foreign experts in the field of fundamental and experimental immunology, clinical immunology, allergology, immunodiagnostics and immunotherapy of infectious, allergy, autoimmune diseases and cancer.
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