Na Cocer Peptides 
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INGINGO ZOSE N'AMAKURU Y’IBICURUZWA BITANZWE KURI URU RUBUGA BISANZWE KUBONA AMAKURU N'INTEGO Zsomes, bifitanye isano rya bugufi no gusaza kwa selile. Epitalon, peptide ngufi ya syntetique ifite ingaruka zo kurwanya gusaza, yashimishije abantu mumyaka yashize.
Ibicuruzwa bitangwa kururu rubuga bigenewe gusa mubushakashatsi bwa vitro. Mu bushakashatsi bwa vitro (Ikilatini: * mu kirahure *, bisobanura mu bikoresho by'ibirahure) bikorerwa 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
Melanotan-1 (MT-1) ni peptide ya peptide ya melanocyte itera imbaraga za ultra-high-efficient, ikora synthique ya hormone melanocortin isanzwe ibaho, imaze kwitabwaho cyane mubikorwa byubwiza. Ibigereranirizo bya Melanocortin bigira uruhare runini mubikorwa byuruhu rwumubiri, bigahura nibyakirwa kugirango bigabanye umusaruro wa melanin. Melanotan - 1 yigana uburyo busanzwe bwa melanocortine, bigira ingaruka kumikorere yuruhu rwuruhu, rukaba arirwo rufatiro rwo gukoreshwa mubikorwa byubwiza.
Igishushanyo 2 Imiterere yimiti ya Melanotan - 1.
Amateka, ubushakashatsi kuri Melanotan-1 bwatangiranye nubushakashatsi bwimbitse bwuburyo bwo kugenzura uruhu. Mu gihe abantu bakurikirana ubwiza bakomeje kwiyongera, cyane cyane ku ngaruka ziterwa n’uruhu, abashakashatsi barushijeho kwibanda ku bintu bishobora kugenga umusaruro wa melanine.
Uburyo bwibikorwa
(1) Guhambira Abakira Melanocortin
Urufunguzo rwimikorere ya Melanotan-1 ruri mubushobozi bwarwo bwo guhuza reseptor ya melanocortine (MC1R). MC1R ni G ya proteine ihujwe na reseptor igaragara cyane cyane hejuru ya melanocytes. Iyo Melanotan-1 ihujwe na MC1R, itera urukurikirane rw'ibimenyetso byo guhererekanya ibimenyetso. Uku guhambira gukora poroteyine G ihujwe na MC1R, nayo igakora adenylate cyclase, bigatuma habaho kwiyongera kurwego rwa kabiri rwintumwa ya cyclic adenosine monophosphate (cAMP). Ubwiyongere bwa cAMP burakomeza gukora protein kinase A (PKA), igenga imvugo ya genoside ya melanin synthesis ifitanye isano na fosifora yibintu byandikirwa hasi, microphthalmia ifitanye isano na transcript (MITF).
Igishushanyo cya 2 Ihuriro hagati yimpinduka nini mubucucike bwa melanin nubucucike bwa melanin kumurongo wo hejuru imbere muri ITT.
(2) Kugena imvugo ya gene ijyanye na synthesis ya melanin
MITF ni ikintu cyingenzi cyo kwandukura inzira ya synthesis ya melanin, ishoboye kugenzura imvugo ya genes nyinshi zifata imisemburo igira uruhare muri synthesis ya melanin, hamwe na tyrosinase ni ngombwa cyane. Tyrosinase ni enzyme igabanya igipimo muri synthesis ya melanin, itera ihinduka rya tirozine buhoro buhoro muri dopaquinone, hanyuma igahuzwa na melanin. Melanotan-1 iteza imbere ibikorwa bya MITF, yongera imvugo ya tyrosinase hamwe nindi misemburo ya melanin ifitanye isano na enzymes, bityo byihutisha inzira ya synthesis ya melanin. Melanotan-1 irashobora kandi kugira ingaruka kumvugo yizindi genes zijyanye na synthesis ya melanin, nka dopa-colorin interconverting enzyme (DCT), nibindi. Iyi misemburo ikora hamwe kugirango iteze imbere melanin synthesis hamwe no kwirundanya, amaherezo biganisha ku ibara ryuruhu rwijimye.
(3) Ingaruka zingirakamaro zinzira zidasanzwe zerekana inzira
Usibye inzira ya cAMP-PKA-MITF yerekana inzira yavuzwe haruguru, Melanotan-1 irashobora kandi kugenga synthesis ya melanin ikoresheje izindi nzira zerekana ibimenyetso. Irashobora guhindura mitogen-ikora protein kinase (MAPK) yerekana inzira. Muri melanocytes, inzira ya MAPK yerekana inzira igira uruhare mugutunganya inzira zitandukanye zibinyabuzima nko gukwirakwiza selile, gutandukanya, no kubaho. Melanotan-1 irashobora gukora inzira ya MAPK yerekana inzira kugirango irusheho guteza imbere ikwirakwizwa rya melanocyte hamwe na synthesis ya melanin. Inzira ya PI3K-Akt yerekana inzira irashobora kandi kuba ifitanye isano n'ingaruka za Melanotan-1. Iyi nzira igira uruhare runini mugukura kwingirabuzimafatizo, kubaho, no kugenzura metabolike, birashoboka gutanga umusingi ukenewe wa metabolike ya synthesis ya melanin muguhindura imikorere ya metabolike.
Uruhare mu nganda zubwiza
(1) Guteza imbere uruhu
Kugaragaza Ingaruka Zo Kuringaniza
Ingaruka zo kwisiga zigaragara cyane za Melanotan-1 nubushobozi bwayo bwo kuzamura uruhu. Ubushakashatsi bwerekanye ko nyuma yo gutanga Melanotan-1 binyuze mu gutera inshinge cyangwa ubundi buryo bukwiye bwo kuyobora, umwijima ugaragara cyane wuruhu urashobora kugaragara mubisomo. Mu bushakashatsi bwarimo abakorerabushake bafite ubuzima buzira umuze, gutera inshinge za Melanotan-1 ku gipimo cya 0.08–0.21 mg / kg byatanzwe ubudahwema iminsi 5 mu byumweru 2 (dosiye 10). Ibisubizo byerekanaga uruhu runini mubice nkuruhanga, amaboko, nijosi ryibisobanuro. Ingaruka yo gutwika ntabwo iterwa no kwangirika kwatewe na UV ahubwo biterwa no kwiyongera kwa endogenous melanin synthesis, bikavamo uruhu runini ndetse rusanzwe.
Ikiringo c'ingaruka
Ingaruka yo gutwika uruhu iterwa na Melanotan-1 ifite urwego runaka rwo gukomeza. Ubushakashatsi bwerekanye ko ingaruka zo gutwika zigeze ku rwego rwo hejuru nyuma yicyumweru kimwe nyuma yubuyobozi, ndetse nibyumweru bitatu nyuma yo kurangiza inshuro icumi, ibara ryuruhu ryakomeje kuba umwijima cyane kuruta mbere yo kuvurwa. Ibi byerekana ko Melanotan-1 iteza imbere gusa synthesis ya melanin ahubwo inerekana ko melanine ikorwa binyuze muri ubu buryo bwa synthesis ishobora kubikwa mu ruhu mugihe runaka, bityo bikagira ingaruka zo kugaragara.
(2) Ingaruka zishobora gukingira uruhu
Uburyo bwo kurinda UV
Melanin ikora nk'inzitizi ikomeye y'uruhu irwanya imirasire ya UV. Mu kongera synthesis ya melanin, Melanotan-1 yongerera imbaraga ubushobozi bwuruhu rwo kwinjiza no gukwirakwiza imirasire ya UV, bityo bikagabanya kwangirika kwatewe na UV kwingirangingo zuruhu. Melanin ikurura ingufu za UV ikayihindura ingufu zumuriro kugirango irekurwe, bityo bigabanye ibyago byo kwangirika kwa UV kwangirika kuri macromolecules yibinyabuzima nka ADN na proteyine. Byongeye kandi, melanin irashobora kugenga sisitemu yumubiri yuruhu kugirango igabanye ibisubizo biterwa na UV, bikarinda uruhu kwangirika.
Ibimenyetso bifitanye isano n'ubushakashatsi
Nubwo ubushakashatsi ku mavuriro ku ngaruka zitaziguye zo kurinda uruhu rwa Melanotan-1 kuri ubu ari buke, ubushobozi bwabwo bwo kurinda UV burashobora gutangwa mu buryo bushyize mu gaciro bushingiye ku mikorere ya physiologique ya melanin na Melanotan-1 yo guteza imbere synthesis ya melanin. Bamwe mu bushakashatsi bwakozwe na vitro bagaragaje ko melanocytes ivurwa na Melanotan-1 igaragaza urugero ruto rw’ubwoko bwa ogisijeni ikora (ROS) kandi bikagabanya igipimo cya apoptose nyuma yo guhura na UV, byerekana ko Melanotan-1 ishobora kongera kwihanganira uruhu imirasire ya UV mu kongera imbaraga za melanine.
(3) Izindi ngaruka zishobora kugaragara kumubiri
Kunoza uruhu
Bamwe bavuga ko Melanotan-1 ishobora kugira ingaruka nziza kumiterere yuruhu. Kwiyongera kwa melanin synthesis birashobora kongera metabolisme selile, bigatera synthesis hamwe no kuvugurura fibre ya kolagen na elastique. Mu bushakashatsi bumwe na bumwe buto bwo kwitegereza, bamwe mu bitabiriye amahugurwa bavuze ko uruhu rwabo rwarushijeho gukomera, rukaba rworoshye, kandi rugaragaza iterambere mu murongo mwiza n’iminkanyari nyuma yo gukoresha Melanotan-1. Ibi bifitanye isano no kugenzura uruhu rwa matrix metabolism rwuruhu rwuruhu rwinzira zerekana ibimenyetso bikora mugihe cya synthesis ya melanin.
Kugabanya ibara ryuruhu
Ubushakashatsi bumwe bwerekanye kandi ko Melanotan-1 ishobora kugira a ingaruka runaka ku ruhu rwinshi. Imiterere yimiterere yuruhu isanzwe ifitanye isano nihungabana muri melanin metabolism. Mugutunganya synthesis ya melanin no kuyikwirakwiza, Melanotan-1 irashobora gufasha gukwirakwiza melanine neza kuruhu, bityo bikagabanya kugaragara kwa pigmentation.
Porogaramu murwego rwuburanga
Nyuma yo guterwa insimburangingo, Melanotan-1 yinjizwa rwose numubiri, ikerekana bioavailable kimwe nubuyobozi bwimitsi. Mu bushakashatsi bwa farumasi bugereranya inzira zitandukanye zubuyobozi, gutera inshinge za Melanotan-1 kuri dosiye ya 0.08-0.21 mg / kg byaviriyemo ibiyobyabwenge byamenyekanye muri plasma, hamwe na plasma igice cyubuzima bwamasaha 0.07–0.79 mugihe cyo kwinjizwa hamwe namasaha 0.8-1.7 mugihe cya β icyiciro. Ibyiza byo guterwa inshinge zirimo ubuyobozi bworoshye ugereranije no gufata neza imiti; icyakora, ifite kandi imbogamizi zimwe na zimwe, nk'ububabare bwaho bwaho, umutuku, hamwe nibindi bitero byatewe.
4. Kugereranya nubundi buryo bwiza bwuburanga
Kugereranya nuburyo gakondo bwo koga izuba
Kwiyuhagira izuba gakondo nuburyo busanzwe bwo kugera ku ngaruka zo gutwika uruhu, ariko ubu buryo bufite ibibi byinshi. Kumara igihe kinini kumirasire ya ultraviolet (UV) byongera ibyago byo kurwara kanseri yuruhu, gufotora, nibindi bihe, mugihe nanone bishobora gutera izuba, gukama, hamwe n’iminkanyari. Melanotan-1-iterwa no guhindagura uruhu igerwaho binyuze muri synthesis ya endogenous melanin synthesis, muburyo bwo kwirinda ibyangiritse biterwa na UV itaziguye. Ariko, kubera ko umutekano wa Melanotan-1 utarashyirwaho neza, ntushobora gusimbuza burundu izuba gakondo nkuburyo bwizewe kandi bwizewe.
Kugereranya nibicuruzwa bya Tanning artificiel
Hariho ibicuruzwa bimwe na bimwe byerekana ibicuruzwa biboneka ku isoko, nk'amavuta yo kwisiga yo kwisiga, ubusanzwe akora na aside amine hejuru yuruhu kugirango areme ibara risa. Ugereranije na Melanotan-1, ibicuruzwa byo gutunganya ibihangano bikora hejuru yuruhu, bikavamo ingaruka zigihe gito kandi bishobora gutera ibibazo nkibara risa cyangwa ridasanzwe. Ku rundi ruhande, Melanotan-1, ihindura ibara ryuruhu imbere imbere muguhindura synthesis ya melanin, birashobora gutanga umusaruro urambye kandi karemano.
Umwanzuro
Nka misemburo ya melanocyte ikangura imisemburo peptide, Melanotan-1 ikora cyane cyane muguhuza imisemburo ya melanocyte itera imisemburo, gukora inzira zerekana ibimenyetso, no kugenzura imiterere ya genes zijyanye na synthesis ya melanin, bityo bigatuma melanine ikomatanya. Kubijyanye n'ingaruka zo kwisiga, biteza imbere neza uruhu rwuruhu hamwe nurwego runaka rwo gukomeza, kandi rushobora no kugira ingaruka zo kurinda uruhu nizindi ngaruka nziza kumiterere yuruhu.
Inkomoko
[1] Habbema L, Halk AB, Neumann M, n'abandi. Ingaruka zo gukoresha mu buryo butemewe gukoresha alpha-melanocyte-itera imisemburo igereranya: gusubiramo [J]. Ikinyamakuru mpuzamahanga cya Dermatology, 2017,56 (10): 975-980.DOI: 10.1111 / ijd.13585.
[2] Fitzgerald LM, Fryer JL, Dwyer T, n'abandi. Ingaruka za MELANOTAN, [Nle (4), D-Phe (7)] - alpha-MSH, kuri synthesis ya melanin mu bantu bafite MC1R ihindura alleles [J]. Peptide, 2006,27 (2): 388-394.DOI: 10.1016 / j.peptide.2004.12.038.
[3] Ugwu S, Blanchard J, Dorr R, n'abandi. Uruhu rwa pigmentation na pharmacokinetics ya melanotan-I mubantu [J]. Biopharmaceutics & Disposition, 1997,18: 259-269.DOI: 10.1002 / (SICI) 1099-081X (199704) 18: 33.0.CO; 2-X.
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