Morphofunctional State of the Large Intestine in Rats under Conditions of Restraint Stress and Administration of Peptide ACTH(4-7)-PGP (Semax)

Svishcheva, M. V.; Mishina, Ye. S.; Медведева, О. А.; Bobyntsev, I. I.; Mukhina, A. Yu.; Калуцкий, П. В.; Andreeva, L. A.; Myasoedov, N. F.

doi:10.1007/s10517-021-05072-z

Cited by 6 publications

(4 citation statements)

References 11 publications

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“…При этом изменение качественного и количественного состава микробиоты может наблюдаться даже после кратковременного стрессорного воздействия [102]. Ранее нами было показано, что хронический иммобилизационный стресс приводил к изменению состава микробиоты толстой кишки в виде уменьшения количества облигатных микроорганизмов и увеличения условно-патогенных [103][104][105][106], которое было ассоциировано с воспалительными изменениями в стенке толстой кишки [107][108][109]. При этом ежедневное внутрибрюшинное введение тафтцина-ПГП и N-синтетического аналога АКТГ, АКТГ4-7-ПГП корригировало стресс-индуцированные изменения как в микробиоте толстой кишки, так и в ее стенке [104,108,109].…”

Section: влияние метаболических факторов микробиоты на морфофункцио-н...unclassified

On mechanisms of increased intestinal wall permeability under stress

Vorvul¹,

Bobyntsev²,

Медведева³

2022

Humans and their Health

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One of the manifestations of the stress reaction in the colon is an increase in the permeability of its wall due to the development of an inflammatory reaction against the background of changes in neuroendocrine regulation and microbiota state. These processes are accompanied by significant changes in humoral homeostasis and cell activity involved in the development of an inflammatory response in the colon wall. We performed a literature review to analyze and summarize the available research data on the mechanisms of stress-induced changes in the intestine at the molecular, cellular and tissue levels involving the regulatory systems of the body. Scientific information was searched in Web Of Science, Scopus, ScienceDirect, Medline, Russian Science Citation Index (RSCI), as well as in the search engines Google Scholar, PubMed, Semantic Scholar, Taylor & Francis, Wiley Online Library and Bielefeld Academic Search Engine (BASE). Wall permeability has been shown to have a rather complex regulation involving corticotropin-releasing factor, mast cells, dendritic cells, eosinophils, macrophages, Substance P, nerve growth factor, neurotensin, microbiota metabolic factors (serotonin, short-chain fatty acids, indole derivatives and conjugated fatty acids), epigenetic mechanisms, the HES1 (Hairy/Enhancer of Split-1) - GR (glucocorticoid receptor), and the stress-associated polarity signaling pathway. Under stress, there is a change in the functioning of these mechanisms, leading to an increase in the permeability of the intestinal wall. It results in translocation of bacteria from the lumen into the underlying layers which causes activation of the immune response with subsequent development of an inflammatory reaction. The presented data testify to the prospects and validity of the development of methods of correction of stress-induced shifts in the colon by influencing the central and local mechanisms of realization of the stress response and the state of the microbiota.

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Section: влияние метаболических факторов микробиоты на морфофункцио-н...unclassified

On mechanisms of increased intestinal wall permeability under stress

Vorvul¹,

Bobyntsev²,

Медведева³

2022

Humans and their Health

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“…Влияние пептида АКТГ 6-9 -Pro-Gly-Pro на морфофункциональное Бюллетень сибирской медицины. 2023; 22 (2): 14-20 ряд его эффектов в условиях хронического иммобилизационного стресса (ХИС) [3][4][5], в том числе на состояние нервной системы в соответствии с представлениями о функциональных взаимосвязях в оси кишечник -мозг [6]. Структурно и функционально родственным семаксу пептидом является АКТГ 6-9 -Pro-Gly-Pro.…”

Section: Introductionunclassified

“…При этом исследования морфофункционального состояния стенки кишки на фоне применения АКТГ 6-9 -ПГП не проводились. Учитывая провоспалительный характер хронического стрессорного воздействия на стенку толстой кишки и противовоспалительный эффект АКТГ 4-7 -ПГП [5], нами выполнено исследование, целью которого являлось изучение морфофункционального состояния стенки толстой кишки у крыс при применении пептида АКТГ 6-9 -ПГП в условиях хронического стресса. После введения АКТГ 6-9 -ПГП в дозе 500 мкг/кг степень выраженности реактивных изменений снижается (рис.…”

Section: Introductionunclassified

Effects of the ACTH<sup>6-9</sup>-Pro-Gly-Pro peptide on the morphofunctional state of rat colon under conditions of chronic restraint stress

et al. 2023

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Aim. To study the morphofunctional state of the colonic wall in rats when using the N–terminal analog of the adrenocorticotropic hormone (ACTH) ACTH6-9-Pro-Gly-Pro (ACTH6-9-PGP) peptide under chronic stress.Materials and methods. The study was performed on 55 male Wistar rats, which were divided into 5 groups (n = 11): group 1 – control group (administration of saline solution without stress); group 2 – chronic restraint stress (CRS) + administration of saline solution; group 3 – CRS + administration of ACTH6-9-PGP at a dose of 5 μg / kg; group 4 – administration of ACTH6-9-PGP at a dose of 50 μg / kg; group 5 – administration of ACTH6-9- PGP at a dose of 500 μg / kg. A histologic examination of the rat colon was performed. The histologic architecture of the colonic wall, the depth of crypts, and the number of goblet cells were assessed. Furthermore, the number of granulocytes, plasma cells, lymphocytes, macrophages, and mast cells was counted.Results. The study demonstrated that chronic (14 days) restraint stress resulted in the development of inflammations in the colonic wall of the animals. Intraperitoneal administration of ACTH6-9-PGP at doses of 50 and 500 μg / kg daily throughout the entire time of stress exposure prevented the development of stress-induced alterations observed in the control animals. At the same time, anti-inflammatory effects of the peptide in the colonic wall and a decrease in the level of corticosterone in the blood serum were noted.Conclusion. The results of this work and data from other studies on the effects of N-terminal analogs of ACTH indicate the need for studying the mechanisms of their effect on inflammation and searching for targets of ACTH6-9-PGP.

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“…Так, отмечалось увеличение уровня тревожности и проявлений депрессивного поведения у экспериментальных животных на различных моделях хронического стрессового воздействия [2-5]. Кроме того, показаны количественные и качественные изменения состава микробиоты толстой кишки [6-9], изменение морфофункционального состояния ее стенки [10][11][12], а также увеличение уровней провоспалительных цитокинов. Также установлено, что хронический иммобилизационный стресс (14 дней) приводил к изменению корреляционных отношений между функциональным состоянием нервной системы и количественным составом кишечной микробиоты [3].…”

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State of nervous system functions of Wistar rats when using peptide taftsin-PGP (selank) in restraint stress

Bobyntsev,

Krivoshlykova,

Medvedeva

et al. 2023

Humans and their Health

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The aim of the study was to investigate the state of functions of the nervous system of Wistar rats upon application of the peptide taftsin-PGP under conditions of chronic stress. Materials and methods. The experiments were performed on 45 male Wistar rats weighing 200-230 g. Selank peptide (Thr-Lys-Pro-Arg-Pro-Gly-Pro) was injected intraperitoneally at doses of 80, 250 and 750 μg/kg 15 min before stressor exposure. Animals were divided into 5 groups (n = 9): 1 - control (non-stressed animals injected with saline); 2 - stress (stressed animals injected with saline); 3-5 - stress+taftsin-PGP at doses of 80, 250 and 750 µg/kg. Animals were stressed for 28 days; from days 15 to 28, they were injected with selank/saline. The neurotropic effects of selank were evaluated in the elevated plus-maze, open field (OF) and forced swimming tests. To assess the severity of stress response, the concentration of corticosterone in rat serum was evaluated using enzyme immunoassay. Results. It was found that 28-day immobilisation stress caused disturbances of nervous system functions in the form of increased anxiety, horizontal, vertical, locomotor activity, emotionality and expression of depressive behaviour, as well as increased concentration of corticosterone in blood serum of experimental animals. Taftsin-PGP administration against the background of preliminary stressing (from the 15th to the 28th day of the experiment) contributed to a decrease in the severity of stress-induced behavioural changes in rats: at a dose of 750 µg/kg the peptide had anxiolytic effect, 250 µg/kg - antidepressant effect. At the same time, these changes occurred against the background of a significant decrease in serum corticosterone level. Conclusion. Thus, selank corrects stress-induced changes in the state of nervous system functions under 28-day restraint stress.

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Morphofunctional State of the Large Intestine in Rats under Conditions of Restraint Stress and Administration of Peptide ACTH(4-7)-PGP (Semax)

Cited by 6 publications

References 11 publications

On mechanisms of increased intestinal wall permeability under stress

On mechanisms of increased intestinal wall permeability under stress

Effects of the ACTH<sup>6-9</sup>-Pro-Gly-Pro peptide on the morphofunctional state of rat colon under conditions of chronic restraint stress

State of nervous system functions of Wistar rats when using peptide taftsin-PGP (selank) in restraint stress

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