Na Cocer Peptides 
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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.
Incamake ya Melanotan-II
Melanotan-II (MT-II) ni imisemburo ya α-melanocyte ikangura imisemburo (α-MSH) igereranya icyiciro cya melanocortine agoniste. MT-II ntabwo ikoreshwa gusa mubikorwa bijyanye no gutwika; mubijyanye nubushakashatsi bwubuvuzi, burimo gushakishwa kubishobora gukoreshwa mukuvura indwara nko kudakora neza.
Igishushanyo 1 Imiterere ya Melanotan-II.
Melanotan-II Uburyo bwibikorwa
MT-II ikora cyane cyane ingaruka zayo muguhuza reseptor ya melanocortine (MCRs). Umuryango wa reseptor ya melanocortin urimo ubwoko bwinshi nka MC1R, MC2R, MC3R, MC4R, na MC5R. MT-II ni melanocortin reseptor agonist idahitamo ishobora guhuza no gukora MCR nyinshi.
Mu ruhu, MT-II ihuza MC1R hejuru ya melanocytes, igakora adenylate cyclase, ikongera urugero rwa AMP (cAMP), bityo igakora protein kinase A (PKA). PKA ikora microphthalmia ifitanye isano na transcript (MITF) ikoresheje fosifora. MITF ni ikintu cy'ingenzi cyandikirwa muri melanin synthesis, Igenzura imvugo ya gen nka tyrosinase, proteyine-1 (TRP-1), na tyrosinase ifitanye isano na poroteyine-2 (TRP-2), ikaba ari imisemburo igira uruhare muri sintezime ya melanin, amaherezo bigatuma uruhu rwiyongera kandi rukagera ku ngaruka zo gutwika uruhu.
Muri sisitemu y'imitsi, MT-II nayo igira ingaruka kuri sisitemu zimwe na zimwe za neuroendocrine. Irashobora gukangura sisitemu yo hagati ya oxytocine. Ubushakashatsi bwerekanye ko inshinge zatewe na MT-II zitera cyane imvugo ya Fos muri neuron nini ya suprachiasmatic nucleus (SON) na paraventricular nucleus (PVN) ya hypothalamus, igisubizo gishobora guterwa no gutera inshinge za melanocortine antagonist SHU-9119. Ibyuma bya elegitoroniki byerekana ko gutera inshinge za MT-II byongera umuriro wa neurone ya oxytocine muri SON ariko ntibitera dendritic oxytocine irekurwa muri SON. Bitewe nubushakashatsi bwibanze bwerekana ko gushyira mu bikorwa mu buryo butaziguye agoniste ya melanocortin ibuza nucleus ya supraoptic nucleus (SON) oxytocine neuron, ingaruka za MT-II zinjira mu mitsi zishobora kuba byibuze zahujwe igice ku buryo butaziguye, birashoboka binyuze mu gukora inyongeramusaruro ziva mu bwonko bwa caudal, aho MT-II nayo yongera imvugo ya Fos.
Byongeye kandi, MT-II ifite uburyo bumwe na bumwe bwibikorwa kuri metabolism yingufu na thermoregulation. Mubushakashatsi bwimbeba, inshinge za intraperitoneal ya MT-II itera hypometabolism ikomeye kandi yigihe gito / hypothermia. Iyi hypothermic phenomenon ibura muri Kit W-sh / W-sh imbeba idafite selile ya mast, byerekana ko selile ya mast ari ngombwa kuri hypothermia iterwa na MT-II. MT-II irashobora gukangura ingirabuzimafatizo ikoresheje uburyo bwa MRGPRB2 bushingiye kandi bushingiye ku buryo bwo kurekura histamine, itanga hypothermia ikoresheje reseptor ya histamine H 1 , kubera ko hitabwa kuri antagonist pyrilamine cyangwa gukuraho reseptor ya H 1 byerekana neza izo ngaruka za hypothermic.
Ingaruka za Melanotan-II
Uruhare muri Pigmentation y'uruhu
Imwe mu ngaruka zigaragara za MT-II ni ugutera kwiyongera kw'ibara ry'uruhu, ni ukuvuga kugera ku ngaruka zo gutwika. Ibitekerezo byatanzwe nabakoresha byerekana ko abitabiriye hafi ya bose bagerageje gutwika hamwe na MT-II bagaragaje umwijima. Ibi byerekana ko MT-II ifite ubwigenge runaka mu gutera pigmentation yuruhu, idashingiye rwose kumirasire ya ultraviolet kugirango itangire imashini ya melanogenezi.Mu bushakashatsi bumwe na bumwe, ubushakashatsi bwakozwe ku ngero z’inyamaswa ndetse no mu bushakashatsi bwakozwe na vitro selile bwerekanye ko MT-II itera melanocytes mu buryo butaziguye, igahindura imiterere ya enzymes zijyanye na sintezime ya melanin, bityo bigatuma ibara rya melanine ryiyongera. Izi ngaruka zitanga ubundi buryo kubashaka umuringa mugihe bahangayikishijwe no kwangirika kwuruhu rwa UV.
Ingaruka kuri Neurobehavior
Kubireba ingaruka zubwonko, MT-II yerekana ibikorwa byinshi. Mu bushakashatsi bwakoresheje zebrafish nk'icyitegererezo, byagaragaye ko n'amafunguro maremare y'amavuta maremare (HF) (amara hafi 1% gusa y'ubuzima bwa zebrafish, cyangwa ibyumweru bitatu) ashobora gutuma umuntu atibuka neza, akazamuka cyane, kandi bikagabanya ubushakashatsi muri zebrafish. MT-II irashobora guhindura ibyo bidasanzwe biterwa nimirire yuzuye amavuta, igasubirana ubwenge bwa zebrafish kwibuka, guhangayika, nimyitwarire yubushakashatsi kurwego rusa nurwego rusanzwe rwimirire.
Mu bushakashatsi bujyanye na autism, ukoresheje urugero rwimbeba y’ababyeyi (MIA) kugirango bigane autism, imbeba za MIA zigaragaza imiterere isa na autism, nkibimenyetso byerekana imyitwarire mbonezamubano, kugabanya itumanaho ryijwi, no kongera imyitwarire isubiramo. Nyuma yiminsi irindwi ivurwa rya MT-II, ibipimo byimyitwarire mbonezamubano mu mbeba za MIA zabagabo byateye imbere, mugihe ibipimo byimibereho yabantu mu mbeba za C57 bifite amateka asanzwe byagaragaje ko nta mpinduka nini byagaragaye nyuma yo kuvurwa MT-II. Ibi birerekana ko MT-II ifite ingaruka zo kuvura mugutezimbere defisite yimyitwarire ya autism, itanga icyerekezo gishya kubushakashatsi bwo kuvura autism.
Igishushanyo cya 2 Imbeba zikuze zumugabo MIA zerekanye ubwiyongere bwimvugo ya reseptor ya oxytocine mumbere ya cingulate cortex.
Ingaruka kuri metabolism yingufu na thermoregulation
MT-II nayo igira ingaruka zikomeye kuri metabolism yingufu na thermoregulation. Mu bushakashatsi bwimbeba, imbeba zifite pituito adenylate cyclase ikora peptide (PACAP) yatanzwe MT-II ikoresheje inshinge za periferique buri munsi ibyumweru bitatu bikurikiranye mugihe cyo kurwanya imbeho. Ibisubizo byerekanaga ko MT-II ishobora kugarura igice ubushobozi bwa termogenezi bwangiritse bwimbeba. Mu gupima igipimo cya norepinephrine iterwa na metabolike, byagaragaye ko ubushobozi bwa thermogenic bwimbeba zavuwe na MT-II bwagaruwe igice. Byongeye kandi, ubuvuzi bwa MT-II bwakosoye inenge mu ikoreshwa rya lipide hifashishijwe imbaraga za adrenergique, byerekana ko MT-II ishobora kugira ingaruka kuri thermogenezesi mu ngingo ya adipose yijimye igenga ibikorwa by’imitsi itera impuhwe, bityo bikagira uruhare mu gukomeza kuringaniza ingufu za metabolike.
MT-II irashobora gutera hypothermia mumbeba mugukora selile ya mast no kurekura histamine. Iyi nzira irerekana uruhare rwa MT-II muburyo bwo kugenzura ubushyuhe.
Ingaruka zishobora kubaho kuri sisitemu yimyororokere
MT-II nayo igira ingaruka kuri sisitemu yimyororokere. Yakozweho ubushakashatsi bwo kuvura imikorere mibi yumugabo, ifitanye isano ningaruka zayo zitera sisitemu yimyororokere.
Gushyira mu bikorwa Melanotan-II
Porogaramu mubikorwa byubwiza
Mu nganda zubwiza, MT-II ikoreshwa cyane cyane nkumukozi wo gutunganya. Hamwe no kwiyongera kwifata ryiza, ryumuringa hamwe nimpungenge ziterwa no kwangirika kwuruhu rwatewe nizuba gakondo (nko gutwika izuba ndetse no kongera ibyago byo kurwara kanseri yuruhu), MT-II yitabiriwe cyane nkibicuruzwa bivugwa ko bigera ku rukuta rudashingiye ku zuba. Ariko, kubera ko itaremezwa ninzego zemewe nka FDA kandi ikaba idafite ubushakashatsi bunini bw’umutekano n’ubushobozi, ikoreshwa ryayo ku isoko ryubwiza rikomeza kuba ahantu h'imvi. Mu bihugu bimwe na bimwe, kugurisha MT-II bitemewe n'amategeko kubwo kwisiga rimwe na rimwe bibaho.
Gusaba mubushakashatsi bwubuvuzi
Mu rwego rwubushakashatsi bwubuvuzi, ikoreshwa rya MT-II ryibanda cyane cyane ku gushakisha uburyo bushobora kuvura indwara zitandukanye. Mu rwego rwo guhungabana kwa neurobehavioral, MT-II yerekanye imbaraga mu kunoza imitekerereze idasanzwe ya neurobehavioral iterwa nimirire yuzuye amavuta muri zebrafish hamwe na defisite yimyitwarire ya autism mu mbeba za MIA zabagabo, zitanga icyerekezo gishya cyubushakashatsi bwo kuvura indwara zifata ubwonko.
Mu bushakashatsi bwakozwe ku mbaraga za metabolisme n’indwara ziterwa na thermoregulation, ingaruka zo gukiza MT-II kuri thermogenezi mu mbeba zabuze PACAP zerekana agaciro kayo mu kuvura indwara ziterwa na metabolike nk’umubyibuho ukabije. Iperereza ryimbitse ku mikorere ya MT-II ku bijyanye n’ingufu zerekana ibimenyetso byerekana imbaraga za metabolisme bishobora kuganisha ku iterambere ry’imiti ivura indwara ziterwa no guhindagurika. Ubushakashatsi bwakozwe ku buryo bushingiye kuri hypothermia iterwa na MT-II bushobora nanone gutuma turushaho gusobanukirwa uburyo bwimikorere ya physiologique ya thermoregulation, bitanga umusingi wamahame yo kuvura indwara zifitanye isano nubushuhe budasanzwe.
Mu rwego rwindwara zimyororokere, ubushakashatsi ku mikoreshereze ya MT-II mu kuvura imikorere mibi y’igitsina, nubwo ikiri mu ntangiriro zayo, itanga uburyo bushya bwo kuvura imikorere mibi y’abagabo.
Umwanzuro
Melanotan-II, nk'imisemburo ya α-melanocyte ikangura imisemburo igereranya, ifite imirimo myinshi y'ibinyabuzima irimo pigmentation y'uruhu, inzira ya neurobehavioral, imbaraga za metabolism, thermoregulation, hamwe na sisitemu yimyororokere. Kubijyanye na pigmentation yuruhu, irashobora gutuma uruhu rwijimye, rutanga inzira yo gukanika. Mu rwego rwubushakashatsi bwubuvuzi, MT-II yerekana ibyifuzo byinshi. Ubushakashatsi ku ndwara zifata ubwonko, imbaraga za metabolisme n'indwara ziterwa na thermoregulation, hamwe na sisitemu yimyororokere itanga icyerekezo gishya cyo kuvura ibi bihe.
Inkomoko
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[5] Peters B, Hadimeri H, Wahlberg R, n'abandi. Melanotan II: impamvu ishobora gutera impyiko: gusuzuma ibitabo na raporo y'imanza [J]. Raporo y'imanza za Cen, 2020,9 (2): 159-161.DOI: 10.1007 / s13730-020-00447-z.
[6] Paiva L, Sabatier N, Leng G, n'abandi. Ingaruka za Melanotan-II ku bwonko bwa Fos Immunoreactivite na Oxytocine Neuronal Igikorwa hamwe nubusembwa mu mbeba [J]. Ikinyamakuru cya Neuroendocrinology, 2017,29 (2) .DOI: 10.1111 / jne.12454.
Ibicuruzwa biboneka mubushakashatsi bukoreshwa gusa:
