{"id":22650,"date":"2024-02-29T21:46:01","date_gmt":"2024-02-29T19:46:01","guid":{"rendered":"https:\/\/xenobg.com\/?p=22650"},"modified":"2024-02-29T21:49:17","modified_gmt":"2024-02-29T19:49:17","slug":"pregnenolon-ima-silen-funktsionalen-efekt-kato-endotoksinovtlr4-antagonist","status":"publish","type":"post","link":"https:\/\/xenobg.com\/ro\/pregnenolon-ima-silen-funktsionalen-efekt-kato-endotoksinovtlr4-antagonist\/","title":{"rendered":"\u041f\u0440\u0435\u0433\u043d\u0435\u043d\u043e\u043b\u043e\u043d\u044a\u0442 \u0438\u043c\u0430 \u0441\u0438\u043b\u0435\u043d(\u0444\u0443\u043d\u043a\u0446\u0438\u043e\u043d\u0430\u043b\u0435\u043d) \u0435\u0444\u0435\u043a\u0442 \u043a\u0430\u0442\u043e \u0435\u043d\u0434\u043e\u0442\u043e\u043a\u0441\u0438\u043d\u043e\u0432(TLR4) \u0430\u043d\u0442\u0430\u0433\u043e\u043d\u0438\u0441\u0442."},"content":{"rendered":"<p>\u0418\u0437\u0433\u043b\u0435\u0436\u0434\u0430, \u0447\u0435 \u043f\u0440\u0435\u0433\u043d\u0435\u043d\u043e\u043b\u043e\u043d\u044a\u0442 \u043d\u0430\u0439-\u043f\u043e\u0441\u043b\u0435 \u0437\u0430\u043f\u043e\u0447\u0432\u0430 \u0434\u0430 \u043f\u0440\u0435\u0434\u0438\u0437\u0432\u0438\u043a\u0432\u0430 \u0438\u043d\u0442\u0435\u0440\u0435\u0441 \u0432 \u043c\u0435\u0434\u0438\u0446\u0438\u043d\u0441\u043a\u0430\u0442\u0430 \u0438\u043d\u0434\u0443\u0441\u0442\u0440\u0438\u044f. \u041d\u0430\u0440\u0435\u0434 \u0441 \u043c\u043d\u043e\u0433\u043e\u0442\u043e \u0438\u0437\u0441\u043b\u0435\u0434\u0432\u0430\u043d\u0438\u044f \u043f\u0440\u0438 \u0440\u0430\u0437\u043b\u0438\u0447\u043d\u0438 \u043f\u0441\u0438\u0445\u0438\u0447\u043d\u0438 \u043f\u0440\u043e\u0431\u043b\u0435\u043c\u0438, \u0432 \u043c\u043e\u043c\u0435\u043d\u0442\u0430 \u0441\u0435 \u043f\u043e\u044f\u0432\u044f\u0432\u0430\u0442 \u043f\u0440\u043e\u0443\u0447\u0432\u0430\u043d\u0438\u044f, \u043a\u043e\u0438\u0442\u043e \u0440\u0430\u0437\u043a\u0440\u0438\u0432\u0430\u0442 \u043d\u0435\u0433\u043e\u0432\u043e\u0442\u043e \u0434\u0435\u0439\u0441\u0442\u0432\u0438\u0435 \u043a\u0430\u0442\u043e \u0435\u043d\u0434\u043e\u0442\u043e\u043a\u0441\u0438\u043d\u043e\u0432 \u0430\u043d\u0442\u0430\u0433\u043e\u043d\u0438\u0441\u0442 (LPS). \u041a\u0430\u043a\u0442\u043e \u043f\u043e\u0432\u0435\u0447\u0435\u0442\u043e \u043f\u043e\u0442\u0440\u0435\u0431\u0438\u0442\u0435\u043b\u0438 \u0432\u044a\u0432 \u0444\u043e\u0440\u0443\u043c\u0438\u0442\u0435 \u0437\u043d\u0430\u044f\u0442, \u0435\u043d\u0434\u043e\u0442\u043e\u043a\u0441\u0438\u043d\u044a\u0442 \u0434\u0435\u0439\u0441\u0442\u0432\u0430 \u0433\u043b\u0430\u0432\u043d\u043e \u0447\u0440\u0435\u0437 \u0430\u043a\u0442\u0438\u0432\u0438\u0440\u0430\u043d\u0435 \u043d\u0430 \u0440\u0435\u0446\u0435\u043f\u0442\u043e\u0440\u0430 TLR4. \u041f\u0440\u0435\u0433\u043d\u0435\u043d\u043e\u043b\u043e\u043d\u044a\u0442 \u043f\u0440\u0435\u0434\u043e\u0442\u0432\u0440\u0430\u0442\u044f\u0432\u0430 &nbsp;\u0430\u043a\u0442\u0438\u0432\u0438\u0440\u0430\u043d\u0435\u0442\u043e \u043d\u0430 TLR4 \u043e\u0442 \u0435\u043d\u0434\u043e\u0442\u043e\u043a\u0441\u0438\u043d. \u0421\u0442\u0430\u0442\u0438\u044f\u0442\u0430 \u043f\u043e\u0441\u043e\u0447\u0432\u0430, \u0447\u0435 \u0442\u043e\u0437\u0438 \u0431\u043b\u043e\u043a\u0438\u0440\u0430\u0449 \u0435\u0444\u0435\u043a\u0442 \u043d\u0430 TLR4 \u043f\u043e\u0441\u0440\u0435\u0434\u0441\u0442\u0432\u043e\u043c \u043f\u0440\u0438\u0435\u043c \u043d\u0430 \u043f\u0440\u0435\u0433\u043d\u0435\u043d\u043e\u043b\u043e\u043d \u043c\u043e\u0436\u0435 \u0434\u0430 \u0433\u043e \u043f\u0440\u0435\u0432\u044a\u0440\u043d\u0435 \u0432 \u0435\u0444\u0435\u043a\u0442\u0438\u0432\u043d\u043e \u0441\u0440\u0435\u0434\u0441\u0442\u0432\u043e \u0437\u0430 \u043b\u0435\u0447\u0435\u043d\u0438\u0435 \u043d\u0430 \u0430\u043b\u043a\u043e\u0445\u043e\u043b\u0438\u0437\u044a\u043c, \u0448\u0438\u0437\u043e\u0444\u0440\u0435\u043d\u0438\u044f, \u0435\u043f\u0438\u043b\u0435\u043f\u0441\u0438\u044f, \u043c\u043d\u043e\u0436\u0435\u0441\u0442\u0432\u0435\u043d\u0430 \u0441\u043a\u043b\u0435\u0440\u043e\u0437\u0430, \u0441\u0435\u043f\u0441\u0438\u0441, \u043f\u043e\u0441\u0442\u0442\u0440\u0430\u0432\u043c\u0430\u0442\u0438\u0447\u0435\u043d \u0441\u0442\u0440\u0435\u0441, \u0410\u043b\u0446\u0445\u0430\u0439\u043c\u0435\u0440&nbsp; \u0438 \u0442.\u043d. \u2013 \u0441 \u0434\u0440\u0443\u0433\u0438 \u0434\u0443\u043c\u0438 \u0437\u0430 \u0432\u0441\u0438\u0447\u043a\u0438 \u0441\u044a\u0441\u0442\u043e\u044f\u043d\u0438\u044f, \u0441\u0432\u044a\u0440\u0437\u0430\u043d\u0438 \u0441 \u0430\u0431\u043d\u043e\u0440\u043c\u0430\u043b\u043d\u043e \u0430\u043a\u0442\u0438\u0432\u0438\u0440\u0430\u043d\u0435 \u043d\u0430 TLR4. \u0410\u043d\u0442\u0430\u0433\u043e\u043d\u0438\u0437\u043c\u044a\u0442 \u043d\u0430 TLR4 \u0441\u044a\u0449\u043e \u043c\u043e\u0436\u0435 \u0434\u0430 \u043e\u0431\u044f\u0441\u043d\u0438 \u043f\u043e\u043b\u0437\u0438\u0442\u0435 \u043e\u0442 \u043f\u0440\u0435\u0433\u043d\u0435\u043d\u043e\u043b\u043e\u043d\u0430 \u043f\u0440\u0438 \u0440\u0435\u0432\u043c\u0430\u0442\u043e\u0438\u0434\u0435\u043d \u0430\u0440\u0442\u0440\u0438\u0442, \u043a\u0430\u043a\u0442\u043e \u0441\u0435 \u0434\u0435\u043c\u043e\u043d\u0441\u0442\u0440\u0438\u0440\u0430 \u0432 \u043c\u043d\u043e\u0436\u0435\u0441\u0442\u0432\u043e \u0438\u0437\u0441\u043b\u0435\u0434\u0432\u0430\u043d\u0438\u044f \u043e\u0442 \u043f\u044a\u0440\u0432\u0430\u0442\u0430 \u043f\u043e\u043b\u043e\u0432\u0438\u043d\u0430 \u043d\u0430 20-\u0442\u0438 \u0432\u0435\u043a. \u0422\u043e\u0432\u0430 \u0438\u0437\u0441\u043b\u0435\u0434\u0432\u0430\u043d\u0435 \u043f\u043e\u043a\u0430\u0437\u0432\u0430, \u0447\u0435 \u043a\u0430\u043a\u0442\u043e \u043f\u0440\u0435\u0433\u043d\u0435\u043d\u043e\u043b\u043e\u043d, \u0442\u0430\u043a\u0430 \u0438 \u043d\u0435\u0433\u043e\u0432\u0438\u044f\u0442 \u043c\u0435\u0442\u0430\u0431\u043e\u043b\u0438\u0442 \u0430\u043b\u043e\u043f\u0440\u0435\u0433\u043d\u0435\u043d\u043e\u043b\u043e\u043d, \u043f\u0440\u0435\u0434\u043e\u0442\u0432\u0440\u0430\u0442\u044f\u0432\u0430\u0442 \u0432\u044a\u0437\u043f\u0430\u043b\u0438\u0442\u0435\u043b\u043d\u0438\u0442\u0435 \u0435\u0444\u0435\u043a\u0442\u0438, \u0441\u0432\u044a\u0440\u0437\u0430\u043d\u0438 \u0441 \u0430\u043a\u0442\u0438\u0432\u0430\u0446\u0438\u044f\u0442\u0430 \u043d\u0430 TLR4. \u0410\u043b\u043e\u043f\u0440\u0435\u0433\u043d\u0435\u043d\u043e\u043b\u043e\u043d\u044a\u0442 \u0438\u0437\u0433\u043b\u0435\u0436\u0434\u0430 \u0438\u043c\u0430&nbsp; \u043f\u043e-\u0441\u0438\u043b\u0435\u043d \u0435\u0444\u0435\u043a\u0442, \u043d\u043e \u0442\u0430\u0437\u0438 \u0440\u0430\u0437\u043b\u0438\u043a\u0430 \u0431\u0438 \u043c\u043e\u0433\u043b\u0430 \u0434\u0430 \u0441\u0435 \u043f\u0440\u0435\u043e\u0434\u043e\u043b\u0435\u0435 \u0447\u0440\u0435\u0437 \u0443\u0432\u0435\u043b\u0438\u0447\u0430\u0432\u0430\u043d\u0435 \u043d\u0430 \u0434\u043e\u0437\u0430\u0442\u0430 \u043f\u0440\u0435\u0433\u043d\u0435\u043d\u043e\u043b\u043e\u043d. \u0422\u044a\u0439 \u043a\u0430\u0442\u043e \u0441\u0438\u043b\u043d\u0438\u0442\u0435 \u0430\u043d\u0442\u0438-\u0432\u044a\u0437\u043f\u0430\u043b\u0438\u0442\u0435\u043b\u043d\u0438 \u0435\u0444\u0435\u043a\u0442\u0438 \u0441\u0435 \u043d\u0430\u0431\u043b\u044e\u0434\u0430\u0432\u0430\u0442 \u043f\u0440\u0438 \u043a\u043e\u043d\u0446\u0435\u043d\u0442\u0440\u0430\u0446\u0438\u044f \u043e\u0442 1 um\/L, \u0442\u043e\u0432\u0430 \u043f\u043e\u0434\u0441\u043a\u0430\u0437\u0432\u0430, \u0447\u0435 \u0447\u043e\u0432\u0435\u0448\u043a\u0438\u0442\u0435 \u0434\u043e\u0437\u0438 \u043e\u0442 30 \u043c\u0433-50 \u043c\u0433 \u0431\u0438 \u0442\u0440\u044f\u0431\u0432\u0430\u043b\u043e \u0434\u0430 \u0441\u0430 \u0434\u043e\u0441\u0442\u0430\u0442\u044a\u0447\u043d\u0438, \u0437\u0430 \u0434\u0430 \u0441\u0435 \u043f\u043e\u0441\u0442\u0438\u0433\u043d\u0435 \u0436\u0435\u043b\u0430\u043d\u0438\u044f\u0442 \u0440\u0435\u0437\u0443\u043b\u0442\u0430\u0442. \u0422\u0443\u043a \u0435 \u043c\u043e\u043c\u0435\u043d\u0442\u044a\u0442 \u0434\u0430 \u0441\u043f\u043e\u043c\u0435\u043d\u0435\u043c,&nbsp; \u0447\u0435 &nbsp;\u0432 \u0442\u043e\u0432\u0430 \u0438\u0437\u0441\u043b\u0435\u0434\u0432\u0430\u043d\u0435 \u043d\u0435 \u0441\u0435 \u0440\u0430\u0437\u0433\u043b\u0435\u0436\u0434\u0430 \u0434\u0435\u0439\u0441\u0442\u0432\u0438\u0435\u0442\u043e \u043d\u0430 \u043f\u0440\u043e\u0433\u0435\u0441\u0442\u0435\u0440\u043e\u043d\u0430, \u043d\u043e \u0441\u044a\u0449\u0435\u0441\u0442\u0432\u0443\u0432\u0430\u0442 \u0440\u0435\u0434\u0438\u0446\u0430 \u0434\u0440\u0443\u0433\u0438, \u043a\u043e\u0438\u0442\u043e \u043e\u0442\u043a\u0440\u0438\u0432\u0430\u0442, \u0447\u0435 \u043f\u0440\u043e\u0433\u0435\u0441\u0442\u0435\u0440\u043e\u043d\u044a\u0442 \u0441\u044a\u0449\u043e \u0435 \u0444\u0443\u043d\u043a\u0446\u0438\u043e\u043d\u0430\u043b\u0435\u043d \u0430\u043d\u0442\u0430\u0433\u043e\u043d\u0438\u0441\u0442 \u043d\u0430 TLR4 \u043f\u0440\u0438 \u043a\u043e\u043d\u0446\u0435\u043d\u0442\u0440\u0430\u0446\u0438\u0438 \u0434\u043e\u0440\u0438 \u043f\u043e-\u043d\u0438\u0441\u043a\u0438 \u043e\u0442 1 uM\/L.<\/p>\n\n\n\n<p><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30647133\" target=\"_blank\" rel=\"noreferrer noopener\">The neurosteroid, pregnenolone promotes degradation of key proteins in the innate immune signalling to suppress inflammation. \u2013 PubMed \u2013 NCBI<\/a><br><a href=\"https:\/\/www.nature.com\/articles\/s41598-018-37409-6\" target=\"_blank\" rel=\"noreferrer noopener\">Endogenous Neurosteroid (3\u00ce\u00b1,5\u00ce\u00b1)3-Hydroxypregnan-20-one Inhibits Toll-like-4 Receptor Activation and Pro-inflammatory Signaling in Macrophages and Brain | Scientific Reports<\/a><br><a href=\"https:\/\/www.eurekalert.org\/pub_releases\/2019-02\/uonc-sdh021319.php\" target=\"_blank\" rel=\"noreferrer noopener\">Scientists discover how neuroactive steroids dampen inflammatory signaling in cells<\/a><br>\u201c\u2026<strong>For the first time, scientists discovered how&nbsp;neuroactive steroids&nbsp;naturally found in the brain and bloodstream&nbsp;inhibit the activity of&nbsp;a specific kind of protein called&nbsp;Toll-like receptors (TLR4), which have been known to play a role in inflammation in many organs, including the brain<\/strong>. This UNC School of Medicine-University of Maryland collaboration, published in Nature&nbsp;<em>Scientific Reports<\/em>, shows how the neurosteroid allopregnanolone prevents the activation of pro-inflammatory proteins important for gene regulation, as well as the creation of cytokines, which are known to be involved in many different inflammatory conditions.&nbsp;<strong>Inflammatory cell signaling in the brain is heightened in many neuropsychiatric conditions, including alcohol use disorder, depression, and posttraumatic stress. It is also seen in sepsis, epilepsy, multiple sclerosis, and Alzheimer\u2019s disease<\/strong>. \u201cIt has been very difficult to treat brain disease that involves inflammation, but&nbsp;<strong>allopregnanolone\u2019s inhibition of TLR4 signaling activation in macrophages and the brain provides hope that we can develop better therapies to help millions of people suffering with these conditions<\/strong>,\u201d said senior author A. Leslie Morrow, PhD, the John Andrews Distinguished Professor in the Departments of Psychiatry and Pharmacology at the UNC School of Medicine.\u201d<\/p>\n\n\n\n<p>\u201c\u2026<strong>Recent studies showed that the neurosteroid compounds pregnenolone and allopregnanolone have therapeutic effects in depression, schizophrenia and PTSD<\/strong>. But until now, scientists didn\u2019t understand how. The UNC-Maryland study suggests that inhibition of inflammatory signaling may contribute to these effects, and inhibition of TLR4 signaling may be a new target for these conditions.\u201d<\/p>\n\n\n\n<p>\u201c\u2026In collaboration with Laure Aurelian, PhD, at the University of Maryland, Morrow and colleagues found that&nbsp;<strong>allopregnanolone inhibits TLR4 activation in macrophages,<\/strong>&nbsp;which are found in white blood cells and part of the immune system, including in the brain. In particular, the researchers found that&nbsp;<strong>allopregnanolone prevents TLR4 binding to MD2 proteins<\/strong>&nbsp;that work together to produce transcription factors that regulate the genes responsible for inflammatory responses in cells and tissues.&nbsp;<strong>Allopregnanolone also tamps down chemokines and cytokines, such as NFkB, HMGB1, MCP-1 and TNF-a,&nbsp;all of which are&nbsp;part of the immune system and&nbsp;involved in many different inflammatory diseases<\/strong>.<\/p>\n\n\n\n<p>\u201c\u2026Morrow and colleagues found that&nbsp;<strong>pregnenolone also inhibited TLR4 signaling in macrophage cells<\/strong>. \u201c<strong>Pregnenolone\u2019s effects in the brain were less pronounced<\/strong>,\u201d Morrow said. \u201c<strong>But inhibition of peripheral inflammation protects the brain as well&nbsp;<\/strong>because systemic inflammation affects organs throughout the body indirectly.\u201d\u201d<\/p>\n\n\n\n<p>Surs\u0103:<\/p>\n\n\n\n<p><a href=\"http:\/\/haidut.me\/?p=17\">http:\/\/haidut.me\/?p=17<\/a><\/p>","protected":false},"excerpt":{"rendered":"<p>\u0418\u0437\u0433\u043b\u0435\u0436\u0434\u0430, \u0447\u0435 \u043f\u0440\u0435\u0433\u043d\u0435\u043d\u043e\u043b\u043e\u043d\u044a\u0442 \u043d\u0430\u0439-\u043f\u043e\u0441\u043b\u0435 \u0437\u0430\u043f\u043e\u0447\u0432\u0430 \u0434\u0430 \u043f\u0440\u0435\u0434\u0438\u0437\u0432\u0438\u043a\u0432\u0430 \u0438\u043d\u0442\u0435\u0440\u0435\u0441 \u0432 \u043c\u0435\u0434\u0438\u0446\u0438\u043d\u0441\u043a\u0430\u0442\u0430 \u0438\u043d\u0434\u0443\u0441\u0442\u0440\u0438\u044f. \u041d\u0430\u0440\u0435\u0434 \u0441 \u043c\u043d\u043e\u0433\u043e\u0442\u043e \u0438\u0437\u0441\u043b\u0435\u0434\u0432\u0430\u043d\u0438\u044f \u043f\u0440\u0438 \u0440\u0430\u0437\u043b\u0438\u0447\u043d\u0438 \u043f\u0441\u0438\u0445\u0438\u0447\u043d\u0438 \u043f\u0440\u043e\u0431\u043b\u0435\u043c\u0438, \u0432 \u043c\u043e\u043c\u0435\u043d\u0442\u0430 \u0441\u0435 \u043f\u043e\u044f\u0432\u044f\u0432\u0430\u0442 \u043f\u0440\u043e\u0443\u0447\u0432\u0430\u043d\u0438\u044f, \u043a\u043e\u0438\u0442\u043e \u0440\u0430\u0437\u043a\u0440\u0438\u0432\u0430\u0442 \u043d\u0435\u0433\u043e\u0432\u043e\u0442\u043e \u0434\u0435\u0439\u0441\u0442\u0432\u0438\u0435 \u043a\u0430\u0442\u043e \u0435\u043d\u0434\u043e\u0442\u043e\u043a\u0441\u0438\u043d\u043e\u0432 \u0430\u043d\u0442\u0430\u0433\u043e\u043d\u0438\u0441\u0442 (LPS). \u041a\u0430\u043a\u0442\u043e \u043f\u043e\u0432\u0435\u0447\u0435\u0442\u043e \u043f\u043e\u0442\u0440\u0435\u0431\u0438\u0442\u0435\u043b\u0438 \u0432\u044a\u0432 \u0444\u043e\u0440\u0443\u043c\u0438\u0442\u0435 \u0437\u043d\u0430\u044f\u0442, \u0435\u043d\u0434\u043e\u0442\u043e\u043a\u0441\u0438\u043d\u044a\u0442 \u0434\u0435\u0439\u0441\u0442\u0432\u0430 \u0433\u043b\u0430\u0432\u043d\u043e \u0447\u0440\u0435\u0437 \u0430\u043a\u0442\u0438\u0432\u0438\u0440\u0430\u043d\u0435 \u043d\u0430 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