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1kits （10Ibikoresho）
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▎ ya Melanotan-2 Imiterere
Inkomoko: PubChem |
Urukurikirane: Ac-Nle-cyclo (Asp-We-D-Phe-Arg-Trp-Lys) -NH₂ Inzira ya molekulari: C 50H 69N 15O.9 Uburemere bwa molekuline: 1024.2 g / mol Numero ya CAS: 121062-08-6 PubChem CID: 92432 Synonyme: MT-II |
▎ Melanotan-2 Ubushakashatsi
Ni ubuhe bushakashatsi bwakozwe na Melanota?
Melanota ni analogue. Ni analogue ya syntetique ya α-melanocyte-itera imisemburo (α-MSH), itegurwa nuburyo bwo guhuza imiti [1] . α-MSH ni imisemburo isanzwe ibaho ifite imikorere itandukanye yumubiri mumubiri wumuntu, harimo no kugenzura ibara ryuruhu. Melanota yashizweho kugirango yigane zimwe mu ngaruka za α-MSH ariko ifite ibikorwa bikomeye nintego zihariye zo gusaba. Melanota yabanje gutunganywa nkibintu bigamije guteza imbere uruhu, ni ukuvuga icyitwa tanning agent. Ubwiyongere bw'abantu bakeneye gukanika, abantu bamwe batangiye gushaka uburyo bwihuta bwijimye bwuruhu batera Melanota. Ubushakashatsi muri urwo rwego bwibanze cyane cyane ku mikorere n'ingaruka zabwo ku ruhu. Kurugero, ubushakashatsi bwerekanye ko Melanota ishobora guhuza reseptor zihariye kuri melanocytes kugirango itume umusaruro wa melanine, bityo umwijima wijimye [2, 3].
Melanota ni iki?
Melanota ni analogue ya syntetique ifitanye isano na hormone itera α-melanocyte (α-MSH). Igikorwa cyayo nyamukuru nukwongera pigmentation yuruhu no kwijimisha uruhu rwabantu. Melanota ikora cyane cyane mugukorana na reseptor ya melanocortine. By'umwihariko, nka melanocortine reseptor agonist idatoranya, irashobora gutuma umusaruro wa melanine mu ruhu, bityo ukagera ku pigmentation y'uruhu, ni ukuvuga ingaruka zo gutwika. Byongeye kandi, irashobora kandi kubyara igitsina gore ubwacyo ningaruka zo gukangura igitsina.
Ni ubuhe buryo bwihariye bwa Melanota mu gutunganya?
Melanota itera uruhu mu guhuza imikoreshereze ya melanocortine 1 kuri melanocytes. Bikekwa ko Melanota yigana ingaruka za melanocortine α-melanocyte-itera imisemburo itera imbaraga (α-MSH) kuri MC1 yakira melanocytes, bikaviramo kwiyongera mu kwerekana poroteyine ya agouti. Melanota itera melanocytes kubyara no gusohora melanin, bityo ikongera uruhu rwuruhu [4] . Irashobora guteza imbere umusaruro wa eumelanine muruhu kugirango igere kuruhu. Ubushakashatsi bwerekanye ko imisemburo ya α-melanocyte itera imbaraga (α-MSH) analogue cyclicale - .
Ni ubuhe buryo bwihariye bwa Melanota mu gutera igitsina no kongera imbaraga mu mibonano mpuzabitsina?
Kwinjiza kwubaka:
Imbeba zatewe aneste, Melanota - ni umwihariko wa melanocortine reseptor agonist - yerekanaga imiti iterwa na dose iterwa no guterwa inshinge (0.1-1 mg / kg) cyangwa hypothalamic paraventricular nucleus infusion (0.1-1 μg). Izi ngaruka zatumye habaho igitsina gore kandi bigabanya ubukererwe bwibintu byambere byabayeho [6] .Ingaruka zishobora kuba zirimo gukora reseptor ya melanocortine muri sisitemu yo hagati yo hagati, bityo bikagenga inzira zifatika zijyanye no kwubaka. Iyo Melanota yatewe inshinge (0.2 μg) kurwego rwa L6 - S1, amplitude yibyabaye iba hejuru. Ibi byerekana ko inzira zifata imitsi kurwego rwumugongo zishobora no kugira uruhare mukwinjira kwa Melanota [6].
Guteza imbere kwubaka:
Nyuma yo gutera inshinge za Melanota (1 mg / kg), igisubizo cya erekile cyatewe no gukurura imitsi yo mu mitsi cyiyongera, bityo kigira uruhare runini mu kwubaka [6] . Nyuma yo gukuraho burundu urunigi rwimpuhwe zimpuhwe, ingaruka zo kuzamura Melanota zivanyweho. Ibi byerekana ko guteza imbere Melanota kwubaka biterwa nubusugire bwurunigi rwimpuhwe. Ibinyuranye, Melanota yatewe muri corpus cavernosum (1 μg) ntiyerekanye ibikorwa byabateza imbere. Guhindura uruti rw'umugongo cyangwa guhinduranya impande zombi z'imitsi yo mu nda cyangwa imitsi ya dorsal y'imboro ntibyigeze bibangamira ibikorwa byo guteza imbere imitsi ya Melanota (1 mg / kg), bikomeza byerekana ko ingaruka ziterwa na Melanota ku iyerekwa ahanini zinyura mu nzira y'impuhwe zifatika aho kuba imitsi ya pelvic cyangwa imitsi ya dorsal [6]..
Gutezimbere imyitwarire ikangura igitsina gore:
Ubushakashatsi bwerekanye ko Melanota agira kandi ingaruka ku myitwarire y’imibonano mpuzabitsina. Imbeba z’abagore, imbeba za ovariectomize zabanjirijwe na estradiol benzoate (EB) na progesterone (P), gutera inshinge za Melanota (1 na 3 mg / kg) byongereye umubare wo gusimbuka, guhubuka, no gutwi kwamatwi, byerekana ko progesterone ishobora gukorana na Melanota kugira ngo yongere imyitwarire y’imibonano mpuzabitsina ku bagore [7].
Ingaruka ya MTII kuri tumorigenicity ya selile ya melanoma.
Inkomoko: Byatangajwe [1]
Melanota nikintu gifite imikorere myinshi nicyerekezo cyubushakashatsi. Ibikurikira bizerekana ubundi bushakashatsi bujyanye na Melanota.
Kwinjiza kwubaka:
Mu bushakashatsi bumwe na bumwe, byagaragaye ko Melanota nayo igira ingaruka kuri sisitemu yimyororokere. Kurugero, Melanota irashobora gutera igitsina kidasanzwe. Bamwe mu barwayi bagize uburibwe bubi nyuma yo guterwa inshinge za Melanota, ndetse banagaragaza ibimenyetso byerekana ko umuntu yishimye cyane, urugero nko kwiyongera k'umutima, umuvuduko ukabije w'amaraso, guhagarika umutima, no kubira ibyuya bikabije [8] .Ibi byerekana ko Melanota ishobora kugira ingaruka ku itangwa ry'amaraso no mu mitsi y'imyororokere ikora ku buryo bwihariye mu mikorere ya erekile. Byongeye kandi, mu bushakashatsi bwakozwe ku nzoka, ibintu bya melanocortine bishobora gutera igihagararo cya nyagasani, ibyo bikaba bisobanurwa nkikimenyetso cyerekana ko imyanya ndangagitsina yiyongera [8] , bikomeza byerekana ko ingaruka za Melanota ku myororokere zishobora kuba zifitanye isano no gukangura imibonano mpuzabitsina no kugenzura imyitwarire y’imibonano mpuzabitsina.
Gutezimbere umusaruro wa melanin:
Nka analogue ya melanocortine, Melanota irashobora guhuza na reseptor ya melanocortine I (MC1R) kugirango iteze imbere umusaruro wa melanin [9] .Bigerwaho ahanini mugutezimbere ikwirakwizwa rya melanocytes no kugenzura ibikorwa bya tyrosinase. Izi ngaruka zo guteza imbere umusaruro wa melanin ziha Melanota agaciro gakoreshwa mubijyanye nuruhu, kurugero, irashobora kugira uruhare mukuvura no gukumira indwara zimwe na zimwe zuruhu.
Ubushakashatsi mubice birwanya ibibyimba:
Mu bushakashatsi bwakozwe ku kurwanya ibibyimba, ubushakashatsi bwakoresheje urugero rwa B16-F10 melanoma bwerekanye ko nubwo Melanota nta ngaruka igira ku ikwirakwizwa ry’uturemangingo twa melanoma, irashobora kubuza neza kwimuka, gutera, hamwe n’ubukoroni bw’ingirabuzimafatizo za melanoma. Gukoresha hafi ya Melanota birashobora kandi guhindura cyane ikibyimba mu mbeba hamwe na melanoma yashizweho. Uburyo bwibikorwa byabwo ni ugutera igenzura rya fosifata na tensin homologi (PTEN) binyuze muri reseptor ya melanocortin 1 (MC1R), bityo bikabuza iterambere rya melanoma kugabanya cyclooxygenase II (COX-2) / prostaglandine E2 (PGE2) yerekana inzira [1].
Ingaruka zo kuvura kuri autism:
Ubushakashatsi bumwe bwakoresheje uburyo bwo gukingira indwara bw’ababyeyi (MIA) bwerekana imbeba ya autism kugirango hamenyekane ubushobozi bwo kuvura melanocortin reseptor 4 agonist M Melanota kubiranga imiterere ya autism mu mbeba z’abagabo bakuze [10] .Imbeba z’abagabo MIA zerekanaga ibimenyetso bisa na autism, birimo ibipimo by’imyitwarire y’imibereho, kugabanya itumanaho ry’ijwi, no kongera imyitwarire isubiramo. Ubuyobozi bwa Melanota ku mbeba za MIA zumugabo iminsi irindwi ikurikiranye byatumye habaho iterambere ryimibare yimibereho. Nta mpinduka nini yagaragaye mubipimo byimyitwarire yabantu mu mbeba za C57 zabagabo zifite amateka asanzwe nyuma yo kuvurwa na Melanota. Byongeye kandi, mu mbeba zisanzwe za C57, nta mpinduka zigeze zihinduka mu myitwarire imeze nk’isubiramo nyuma yo kuvurwa na Melanota, ariko habayeho kugabanuka gukabije kwibiro byumubiri nyuma yo kuvurwa. Aya makuru yerekana ko Melanota ari imiti ikora neza ishobora kuzamura defisite yimyitwarire ya autism muburyo bwa autism yimbeba zikuze za MIA zikuze.
Guhindura ubumuga bwo kwibuka:
Ubushakashatsi bwerekanye ko indyo yuzuye ibinure (HF) byagaragaye ko byongera ibyago byo kwangirika kwimitsi nindwara zifata ubwonko. Ubu bushakashatsi bwakoze ubushakashatsi ku isano iri hagati yimirire, Melanota yibasira reseptor ya melanocortine, n imyitwarire ya zebrafish [11] . Igitangaje, niyo indyo yigihe gito HF yamaze hafi 1% yubuzima bwa zebrafish yagize ingaruka zikomeye ziterambere. Ugereranije na zebrafish yagaburiwe indyo igenzura, zebrafish yagaburiye indyo ya HF yerekanaga kutamenya neza kumenyekana, kongera amaganya, no kugabanya ubushakashatsi nyuma yibyumweru bitatu gusa. Kandi ibi bidasanzwe byatewe nimirire ya HF byahinduwe na Melanota. Inyamaswa zagaburiye indyo ya HF kandi zivurwa na Melanota zerekanaga kwibuka, kwibuka, imyitwarire nubushakashatsi busa nubw'itsinda rishinzwe kugenzura. Ubu bushakashatsi butanga ibimenyetso byerekana ko n'indyo ya HF y'igihe gito ishobora kugira ingaruka ku kwibuka no ku mutima, kandi ni ubushakashatsi bwa mbere bwerekana ko Melanota ashobora guhindura izo mpinduka.
Kugena imyitwarire mbonezamubano:
Mu rwego rw’ubushakashatsi bwa neuroscience, byagaragaye ko Melanotan-II ishobora kugenga imyitwarire y’imibereho itera reseptor ya melanocortine hanyuma igakora sisitemu yo hagati ya oxytocine [12] . By'umwihariko, nyuma yubuyobozi bwa sisitemu ya Melanota, gutera inshinge aho kuba imiyoborere yimbere ya Melanota birashobora gutera cyane imvugo ya Fos muri neurone ya magnocellular nucleus ya supraoptic nucleus (SON) na paraventricular nucleus (PVN) ya hypothalamus, kandi iki gisubizo gishobora gushimangirwa no kwitegura hamwe na melanocortin 911. Ibyuma bya elegitoroniki byerekanaga ko gutera inshinge za Melanota bishobora kongera umuvuduko wo kurasa kwa neuron ya oxytocine muri SON. Ibi byerekana ko Melanota igira ingaruka kuri sisitemu ya oxytocine ijyanye nimyitwarire mbonezamubano muri sisitemu yimitsi, kandi uburyo bwayo bwo gukora bushobora kuba uguhindura ibikorwa no gusohora neuron ya oxytocine ukoresheje reseptor zihariye hamwe ninzira zerekana inzira.
Ubushakashatsi ku mubyibuho ukabije n'ubuzima bwa metabolike:
Ku bijyanye n'umubyibuho ukabije n'ubuzima bwa metabolike, ubushakashatsi bumwe na bumwe bwakoresheje urugero rwa genoside ya pituito adenylate cyclase-ikora polypeptide (PACAP) -imbeba zidafite akamaro kandi isanga melanocortin reseptor agonist Melanota ishobora gutabara igice cy’ubushobozi bw’ubushyuhe bw’imbeba zabuze PACAP mu gihe cyo kurwanya imbeho. Ibi byerekana ko PACAP ishobora kugira uruhare hejuru ya sisitemu ya melanocortine, ikagenga ibikorwa byimpuhwe zimpuhwe za tissue adipose tissue yimbeba, bityo bikagira ingaruka kumubyibuho ukabije nubuzima bwa metabolike [13].
Kugena metabolism n'ubushyuhe bw'umubiri:
Melanota nayo igira ingaruka zikomeye kuri sisitemu ya endocrine. Kurugero, ubuyobozi bwa intraperitoneal ya Melanota ku mbeba bushobora gutera hypometabolism yimbitse kandi yigihe gito / hypothermia [14] .Abanyeshuri berekanye ko mu mbeba zitagira selile ya mast, hypothermia yatewe na Melanota ikurwaho, byerekana ko hakenewe uruhare rwa selile mast. Melanota itera hypothermia mu mbeba ikora selile ya mast no gukangura reseptor ya histamine 1, kandi uburyo bwayo bukora burimo imikoranire yibintu byinshi bya endocrine na reseptors.
Mu gusoza, nkibintu bya sintetike byakuruye abantu benshi, Melanota yerekana ibintu byihariye mubice byinshi. Mu rwego rwuruhu, muguhuza reseptor zihariye kuri melanocytes, irashobora guteza imbere neza umusaruro wa melanin, igatanga uburyo budasanzwe bwo gutwika abifuza kumera neza kumuringa. Ugereranije no gukanika kumara igihe kinini uhura nimirasire ya ultraviolet, Melanota irashobora kwirinda kwangirika kwimirasire ya ultraviolet kuruhu kandi bikagabanya ingaruka zishobora guterwa nizuba, gusaza kwuruhu, ndetse na kanseri yuruhu.
Urebye imikorere yimibonano mpuzabitsina, Melanota igira ingaruka nziza mukubyutsa igitsina gore ubwacyo no kuzamura imibonano mpuzabitsina. Iki nigisubizo cyiza kubantu bamwe bafite imikorere mibi yimibonano mpuzabitsina cyangwa abizera kuzamura imibonano mpuzabitsina. Irashobora kugera ku ngaruka nziza ku mikorere yimibonano mpuzabitsina ukoresheje inzira zihariye z’imyakura muri sisitemu yo hagati na peripheri ya nervice no kugenzura imiyoboro ya neurotransmitter hamwe niyakira, itanga uburyo bushya bwo kuzamura ubuzima bwimibonano mpuzabitsina.
Mu bushakashatsi ku mubyibuho ukabije n’ubuzima bwa metabolike, Melanota yerekana kandi ibyiza bishobora kuba. Irashobora kugenga ingufu za metabolisme nubushyuhe bwumubiri kandi ikagira ingaruka nziza kumikorere idahwitse yimikorere ya adipose yumubyibuho ukabije. Itanga icyerekezo gishya cy’ubushakashatsi mu kuvura umubyibuho ukabije no gucunga ubuzima bw’imikorere ya metabolike, ifasha mu gushyiraho ingamba nshya zo kuvura no kuzamura ubuzima bw’abarwayi bafite umubyibuho ukabije.
Ibyerekeye Umwanditsi
Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.
Umwanditsi w'ikinyamakuru
Cousen, P numushakashatsi ufite intego yibanze mubijyanye na Dermatology Allergy. Ibikorwa bye muri iyi domeni byahujwe n’imiryango myinshi, harimo Tees Hosp NHS Fdn Trust, Ibitaro bya Kaminuza bya James Cook, Ibitaro bya Royal Cornwall, Kaminuza ya Sheffield, na Royal Hosp. Usibye ubuhanga bwe bwibanze muri Dermatology Allergie, Cousen, ubushakashatsi bwa P nibikorwa birashoboka ko bigera no mubice bifitanye isano nka immunologiya, urebye isano iri hagati yimikorere ya allergique na sisitemu yumubiri. Ibi birashobora kuba bikubiyemo kwiga ubudahangarwa bw'umubiri buganisha ku ruhu rwa allergique no gushakisha uburyo bushya bwo kuvura bwo guhindura ibisubizo.
Byongeye kandi, ubushakashatsi bwe bushobora kuba bukubiyemo ibizamini byo kwa muganga bivura uburyo bushya bwo kuvura dermatologiya, ubushakashatsi ku mikorere y’inzitizi y’uruhu n’uruhare rwayo mu gukumira allergie, no gukora iperereza ku bintu bikomoka ku ngirabuzima fatizo ziteganya abantu allergie y’uruhu. Byongeye kandi, urebye imiterere itandukanye yubushakashatsi bwubuzima, ashobora gufatanya ninzobere mu zindi nzego nka farumasi, microbiologiya (yiga ingaruka za mikorobe y’uruhu kuri allergie), ndetse na psychologiya (gusuzuma ingaruka zo mu mutwe ziterwa na allergie y’uruhu idakira), bityo bikagira uruhare mu gusobanukirwa no gucunga neza indwara ziterwa na dermatologiya. Cousen, P yanditse kurutonde rwerekana [4].
