Na Cocer Peptides 
hashize iminsi 23
INGINGO ZOSE N'AMAKURU Y’IBICURUZWA BITANZWE KURI URU RUBUGA BISANZWE KUBONA AMAKURU N'INTEGO Z'UBUREZI.
Ibicuruzwa byatanzwe kururu rubuga bigenewe gusa mubushakashatsi bwa vitro. Mu bushakashatsi bwa vitro (Ikilatini: * mu kirahure *, bisobanura mu bikoresho by'ibirahure) bikorwa hanze y'umubiri w'umuntu. Ibicuruzwa ntabwo ari imiti, ntabwo byemejwe n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA), kandi ntigomba gukoreshwa mu gukumira, kuvura, cyangwa gukiza indwara iyo ari yo yose y’ubuvuzi, indwara, cyangwa indwara. Birabujijwe rwose n'amategeko kwinjiza ibyo bicuruzwa mumubiri wabantu cyangwa inyamaswa muburyo ubwo aribwo bwose.
Gusaza, nkibikorwa byanze bikunze mubinyabuzima bizima, bimaze igihe kinini byibandwaho mubushakashatsi bwa siyansi. Mugihe ibinyabuzima bigenda bisaza, selile zinjira buhoro buhoro muri senescent, kandi kwirundanya kwingirabuzimafatizo bishobora kugira ingaruka mbi kumikorere isanzwe yimitsi ningingo, biganisha ku ndwara zitandukanye ziterwa nimyaka. FOX04 - DRI ni ingirakamaro mu gukuraho selile.
Incamake
DSIP peptide, Delta-Gusinzira-Itera Peptide, ni neuro-igenga peptide bio-igenzura. Itera gahunda yo gusinzira. Byongeye kandi, bigira ingaruka kumiterere yubushyuhe bwumubiri, umuvuduko wumutima, umuvuduko wamaraso, kurenga ububabare, hamwe na sisitemu ya lymphatic, hamwe nizi ngaruka zerekana injyana ya circadian.
Uburyo bwibikorwa bya DSIP Peptide kuryama
Amabwiriza ya Neurotransmitter
5-Hydroxytryptamine (5-HT): 5-HT ningirakamaro ya neurotransmitter ifitanye isano rya bugufi no kugenzura ibitotsi. Muri leta idasinzira, nka PCPA iterwa no kudasinzira, urwego 5-HT rwaragabanutse cyane. Ubushakashatsi bwerekana ko peptide ya DSIP ishobora kongera urugero rwa 5-HT mubice bya hippocampal, bityo igasinzira neza. 5-HT irashobora kugenga imitekerereze ya neuronal ikora muburyo butandukanye bwo kwakirwa, bityo bikagira ingaruka kumyuka yo gukanguka. 5-HT1A yakira agoniste irashobora guteza imbere ibitotsi byihuse (NREM) ibitotsi, mugihe antagonist 5-HT2A yakira bishobora kugabanya igihe cyo kubyuka, kandi ikongera igihe cyo gusinzira. Peptide ya DSIP irashobora kugira ingaruka kubitotsi muguhindura irekurwa, reuptake, cyangwa imikoranire nabakira 5-HT.
Dopamine (DA): Dopamine nayo igira uruhare runini mugutunganya ibitotsi. Mubihe bisanzwe, ibikorwa bya neuron ya dopaminergique bigira uruhare mugukomeza gukanguka. Ubusumbane mu rwego rwa dopamine burashobora gutera uburwayi. Muburyo bumwe bwo kudasinzira, urugero rwa dopamine rugabanuka, kandi peptide ya DSIP irashobora kugarura igice cya dopamine. Dopamine igenga ibimenyetso byerekana imitsi ihuza reseptor zitandukanye. Peptide ya DSIP irashobora kunoza ibitotsi muguhindura ibikorwa bya neuron ya dopaminergique, igenga synthesis ya dopamine, kurekura, cyangwa metabolism. Irashobora gukora kuri enzymes zingenzi zigira uruhare muri synthesis ya dopamine, nka hydroxylase ya tyrosine, bigira ingaruka ku gipimo cya synthesis ya dopamine bityo bikagira ingaruka ku gusinzira-kubyuka.
Glutamate (Glu): Glutamate nicyo kintu cyambere gishimisha neurotransmitter muri sisitemu yo hagati. Mugihe cyo kudasinzira, urwego glutamate rushobora guhinduka. Ubushakashatsi bwa siyansi bwerekanye ko peptide ya DSIP ishobora kugabanya urugero rwa glutamate mu ngingo za hippocampal, bikongera urugero rwa glutamate mu ngero zimwe na zimwe. Glutamate igenga imitekerereze ya neuronal ihuza reseptor ya ionotropique na metabotropic glutamate. Peptide ya DSIP irashobora kugumana uburinganire bwimikorere ya neuronal muguhindura imikorere ya glutamate cyangwa guhindura glutamate no gufata uburyo, bityo bikagira ingaruka nziza mubitotsi. Barashobora guhindura ibikorwa byabatwara glutamate kugirango bagenzure glutamate idasanzwe, birinda urwego rukabije cyangwa rudahagije kutagira ingaruka mbi kubitotsi.
Melatonin (MT): Melatonin ni imisemburo ya amine isohorwa na glande ya pineine igira uruhare runini mugutunganya ukwezi gusinzira. Muburyo bwimbeba yo kudasinzira, urugero rwa melatonine muri hippocampus rwaragabanutse cyane, kandi peptide ya DSIP yashoboye kongera urugero rwa melatonine. Melatonin igenga injyana ya circadian no gusinzira ihuza reseptor ya MT1 na MT2. DSIP irashobora gukoresha ingaruka zayo mugusinzira muguhindura melatonin synthesis hamwe no gusohora muri glandine, cyangwa muguhindura imvugo nimikorere yabakira melatonine. Irashobora kugenzura ibikorwa byimisemburo yingenzi igira uruhare muri synthesis ya melatonin, nka aromatase N-acetyltransferase (AANAT), bityo bikagira ingaruka kuri synthesis ya melatonin.
Igishushanyo 2 Kugaragaza FOXO4 mubizamini byabantu byagaragaye na immunofluorescent yanduye.
Ingaruka ku ngirabuzimafatizo
Mu buryo bwa PCPA buterwa no kudasinzira cyane, HE yerekana ko imbeba z'itsinda ry'icyitegererezo zagaragaje cyane imyanya myanya ndangagitsina, ingano ntoya, morfologiya idasanzwe, hamwe na matrise idakabije mu ngingo ya hippocampal. Ibinyuranye, itsinda rya DSIP ryavuwe na peptide (nka peptide yo gusinzira rifatanije nitsinda ryinjira mu bwoko bwa peptide P-DSIP) ryerekanye ko imyanya yagabanijwe hagati y’imitsi, gahunda itondekanya ingirabuzimafatizo, hamwe no gukwirakwiza kimwe mu ngingo ya hippocampal. Ibi byerekana ko peptide ya DSIP ishobora kunoza ibitotsi byatewe na neurone ya hippocampal, ikagumana imiterere isanzwe n’imiterere, bityo bigatuma imikorere yabo isanzwe yumubiri, ikanorohereza kugenzura ibitotsi. Imiterere isanzwe ya neuron niyo shingiro ryo kwanduza ibimenyetso no guhuza. Ingaruka zo kurinda peptide ya DSIP kuri selile ya neuronal irashobora gufasha kugarura imikorere isanzwe yinzira zifatika zijyanye no gusinzira.
DSIP peptide irashobora guhindura ibikorwa bya neuronal electrophysiologique. Neuron yohereza amakuru itanga ubushobozi bwibikorwa, kandi imikorere yamashanyarazi ya neuron ihinduka mugihe cyo gusinzira. Peptide ya DSIP irashobora kugenga imiyoboro ya ion kuri selile ya neuronal selile, igahindura umunezero wa neuronal hamwe nigihe cyo kurasa, bityo bikagira ingaruka kubitotsi. Bashobora kongera ibikorwa byinzira zimwe na zimwe za potasiyumu, bigatuma neurone ikunda kwinjira muburyo bwo kuruhuka no guteza imbere ibitotsi.
Inzitizi zijyanye n'amaraso n'ubwonko
Inzitizi y'amaraso n'ubwonko (BBB) ni inzitizi ikomeye hagati yamaraso nubwonko bwubwonko, bikabuza kwinjiza ibintu byinshi biva mumaraso mubice byubwonko. Metabolism ya DSIP peptide kuri bariyeri yamaraso-ubwonko iterwa na aminopeptidase. Mu ngirabuzimafatizo zifite ubwonko bwa microcascular endothelial selile (BBMEC, urugero rwerekana inzitizi yubwonko bwamaraso), peptidyl dipeptidase A irashobora kandi guhinduranya DSIP ikoresheje hydrolyzing dipeptide cyangwa tripeptide ikomoka kuri karubasi ya terefone ya nonapeptide. Mugushyiramo peptidyl dipeptidase A inhibitor (nka capopril) hamwe na inhibitori ya aminopeptidase (nka besartan), metabolism ya DSIP muri BBMECs irashobora guhagarara neza rwose, byerekana ko muguhindura imikorere yiyi misemburo, peptide nyinshi za DSIP zishobora kurenga inzitizi yubwonko bwamaraso kandi zikagera kumitsi yubwonko kugirango zikore ingaruka zogusinzira. Ubushakashatsi bwagerageje guhuza peptide ya DSIP na peptide ishoboye kurenga inzitizi yubwonko bwamaraso (nka CBBBP) kugirango ikore peptide ya DSIP-CBBBP. Iyi peptide ya fusion irashobora kugenzura neza urwego rwa neurotransmitter, nka 5-HT, glutamate, dopamine, na melatonine, bikavamo ingaruka nziza mugutezimbere ibitotsi. Muguhindura ubushobozi bwa peptide ya DSIP kurenga inzitizi yubwonko bwamaraso, ingaruka zabyo mugusinzira zirashobora kwiyongera.
Uruhare rwa DSIP peptide mugutezimbere ibitotsi
1. Kongera igihe cyose cyo gusinzira
Mu bushakashatsi bw’inyamaswa, peptide ya DSIP yerekanye ubushobozi bwo kongera igihe cyose cyo gusinzira mu nyamaswa, tutitaye ko yatanzwe binyuze mu nzira zinjira cyangwa izuru. Mu bushakashatsi bwakorewe muri Nouvelle-Zélande inkwavu zera, gutera inshinge peptide ya DSIP byatumye habaho kwiyongera cyane mu gihe cyo gusinzira ugereranije nitsinda rishinzwe kugenzura saline. Ubuyobozi bwa Intranasal bwagize akamaro kanini, hamwe nitsinda ryimbere muri Nouvelle-Zélande inkwavu zera zerekana igihe kinini cyo gusinzira kuruta itsinda rya saline. Ibi byerekana ko peptide ya DSIP ishobora guteza imbere gusinzira kwinyamaswa no gukomeza gusinzira igihe kirekire. Kwiyongera kwigihe cyose cyo gusinzira ningirakamaro mugukiza kwumubiri no kubungabunga imikorere isanzwe yumubiri, kuko ituma ingingo zose na sisitemu biruhuka bihagije, bifasha mugusana ingirangingo, kugenzura sisitemu ya endocrine, nibindi bikorwa.
Mu buryo bw'imbeba bwerekanwe na hypoxia idakira (HH), hakozwe interineti ya fosifori DSIP peptide (p-DSIP). Ukurikije ibisubizo, p-DSIP yongereye imbaraga ibitotsi byihuta (NREM) no gusinzira byihuse (REM) imbeba, byongera igihe cyo gusinzira. Ibi byerekana ko peptide ya DSIP itera gusinzira muburyo butandukanye bwo gusinzira, kunoza imiterere yibitotsi no kongera ibitotsi.
2. Kongera igihe cyo gusinzira gahoro gahoro
Gusinzira gahoro gahoro (SWS), bizwi kandi ko gusinzira cyane, ni ngombwa mu gukira no gusana umubiri. DSIP peptide yongerera cyane igihe cyo gusinzira gahoro gahoro. Mu bushakashatsi bwakozwe na Nouvelle-Zélande inkwavu zera, haba mu mitsi no mu miyoborere ya DSIP byatumye habaho igihe kinini cyo gusinzira buhoro buhoro mu itsinda rivuwe ugereranije n'itsinda rishinzwe kugenzura saline. Mugihe cyo gusinzira gahoro gahoro, umuvuduko wa metabolike uragabanuka, nibikorwa bya physiologique nkumutima wumutima no guhumeka bigenda gahoro, bigatuma umubiri ugira uruhare mukwisana no kubika ingufu. Peptide ya DSIP irashobora kongera igihe cyo gusinzira gahoro gahoro, bityo ikongerera umubiri imbaraga zo gukira, kugabanya umunaniro, no gukomeza ubudahangarwa.
Urebye kuri neurobiologique, peptide ya DSIP irashobora kugenga urugero rwa neurotransmitter, ikongera urugero rwa 5-HT na melatonine, kandi ikabuza kwinezeza bikabije mu bwonko, bityo bigatuma itangira no gukomeza gusinzira buhoro. Ingaruka zayo zo kurinda ingirabuzimafatizo, zigumana imiterere n'imikorere isanzwe, nazo zigira uruhare mu kurema ibidukikije bifasha gusinzira buhoro.
3. Kunoza imyitwarire ijyanye no gusinzira
Mu bushakashatsi bwimyitwarire, nkikizamini cyo gufungura umurima, hejuru hiyongereyeho na test ya test, hamwe na test yo guhagarika umurizo, peptide ya DSIP yerekanye iterambere ryinshi mubikorwa byimyitwarire yinyamaswa zidasinzira. Mu kizamini cyo kumugaragaro, imbeba zitsinda ryerekanye ko zagabanije cyane intera nigihe cyo gukora, mugihe imbeba zavuwe na peptide ya DSIP (urugero, itsinda rya P-DSIP) zagaragaje cyane intera yimodoka nigihe cyo gukora, byerekana ko peptide DSIP ishobora kuzamura ubushobozi bwibikorwa byimbeba zidasinzira kandi bikagabanya guhagarika ibikorwa biterwa no kudasinzira. Mugihe cyo hejuru wongeyeho maze ikizamini, inshuro imbeba zitsinda ryintangarugero zinjiye mukuboko gukinguye kandi umwanya umara mumaboko afunguye wagabanutse cyane. Ariko, nyuma yubuyobozi bwa peptide ya DSIP, nko mumatsinda ya P-DSIP, inshuro imbeba zinjiye mumaboko yuguruye kandi umwanya umara mumaboko yuguruye wiyongereye cyane, byerekana ko peptide DSIP ishobora kunoza imyitwarire imeze nkimpungenge ku mbeba zidasinzira. Mu kizamini cyo guhagarika umurizo, imbeba zicyitegererezo zerekana ubwiyongere bukabije bwigihe cyo kudahagarara no kugabanuka cyane mugihe cyurugamba. Ariko, nyuma yubuyobozi bwa peptide ya DSIP (nkitsinda rya GABA, itsinda rya P-DSIP, nitsinda rya DSIP), imbeba zagaragaje igabanuka ryigihe cyigihe cyo kutimuka ndetse n’ubwiyongere bukabije bwigihe cyurugamba, byerekana ko peptide DSIP ishobora kunoza imyitwarire isa niyihebye ku mbeba zidasinzira. DSIP peptide irashobora kunoza ibibazo byamarangamutima nimyitwarire iterwa no kudasinzira.
Porogaramu ya DSIP Peptide mugutunganya ibitotsi
Mu bushakashatsi bw’amavuriro, mu bushakashatsi bumwe na bumwe bwakorewe mu mavuriro, nyuma yo gutanga imiti ifitanye isano na DSIP peptide ku barwayi badasinzira, ibitotsi by’abarwayi bamwe na bamwe byateye imbere ku buryo butandukanye, nko gusinzira igihe gito cyo gutangira, kongera ibitotsi, no kugabanya kubyuka nijoro. Byongeye kandi, DSIP peptide irashobora gukoreshwa wenyine mukuvura kudasinzira cyangwa hamwe nindi miti gakondo yo gusinzira. Ubushakashatsi bwerekana ko iyo uhujwe n’imiti imwe n'imwe igabanya ubukana cyangwa imiti igabanya ubukana, peptide ya DSIP igaragaza ingaruka zifatika, bigatuma neza ibitotsi by’abarwayi ndetse n’amarangamutima. Iyo ikoreshejwe ifatanije na benzodiazepine, peptide ya DSIP irashobora kugabanya urugero rwa benzodiazepine, kugabanya ibyago byo kutitwara nabi, no kongera imbaraga zo kuvura.
Umwanzuro
Nkumuteguro usanzwe usinzira, peptide ya DSIP yerekana imikorere muburyo bwo kugenzura ibitotsi, ingaruka zo gusinzira, hamwe nibisabwa.
Inkomoko
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[4] Yehuda S, Carasso R L. DSIP - igikoresho cyo gukora iperereza ku buryo bwo gusinzira: gusubiramo [J]. Ikinyamakuru mpuzamahanga cya Neuroscience, 1988,38 (3-4): 345-353.DOI: 10.3109 / 00207458808990695.
[5] Obál FJ, Kovalzon VM, Kalikhevich VN, n'abandi. Imiterere-ibikorwa mubikorwa byingaruka za delta-ibitotsi-bitera peptide (DSIP) kubitotsi byimbeba [J]. Pharmacology Biochemie nimyitwarire, 1986,24 (4): 889-894.DOI: 10.1016 / 0091-3057 (86) 90432-6.
Ibicuruzwa biboneka mubushakashatsi bukoreshwa gusa:
