Los ntawm Cocer Peptides 
27 hnub dhau los
Tag nrho cov kab lus thiab cov ntaub ntawv ntawm cov khoom lag luam muab rau ntawm lub vev xaib no tsuas yog rau cov ntaub ntawv tshaj tawm kev tshaj tawm thiab cov hom phiaj kev kawm.
Cov khoom muab rau hauv lub vev xaib no yog npaj tshwj xeeb rau kev tshawb fawb hauv vitro. Kev tshawb fawb hauv vitro (Latin: * hauv iav *, lub ntsiab lus hauv iav) yog ua los ntawm tib neeg lub cev. Cov khoom no tsis yog tshuaj, tsis tau txais kev pom zoo los ntawm US Food and Drug Administration (FDA), thiab yuav tsum tsis txhob siv los tiv thaiv, kho, lossis kho txhua yam mob, kab mob, lossis mob. Nws raug txwv nruj raws li txoj cai los qhia cov khoom no rau hauv tib neeg lossis tsiaj lub cev hauv txhua daim ntawv.
Txheej txheem cej luam
Melanotan-1 (MT-1) yog ib qho ultra-high-efficiency hluavtaws melanocyte-stimulating peptide, ib tug hluavtaws formulation ntawm ib txwm tshwm sim hormone melanocortin, uas tau garnered tseem ceeb nyob rau hauv kev zoo nkauj kev lag luam. Melanocortin analogues ua lub luag haujlwm tseem ceeb hauv cov txheej txheem ntawm daim tawv nqaij, cuam tshuam nrog cov receptors tshwj xeeb los tswj cov khoom melanin. Melanotan - 1 ua raws li cov txheej txheem ntuj tsim ntawm melanocortin, cuam tshuam rau daim tawv nqaij cov txheej txheem pigmentation, uas yog lub hauv paus rau nws daim ntawv thov hauv kev lag luam kev zoo nkauj.
Daim duab 2 Cov qauv tshuaj ntawm Melanotan - 1.
Keeb kwm, kev tshawb fawb ntawm Melanotan-1 tau pib nrog kev tshawb nrhiav qhov tob ntawm cov tawv nqaij pigmentation cov txheej txheem. Raws li tib neeg txoj kev nrhiav kev zoo nkauj tseem nce ntxiv, tshwj xeeb yog qhov kev thov rau cov tawv nqaij tanning teebmeem, cov kws tshawb fawb tau tsom mus rau cov tshuaj uas tuaj yeem tswj cov tshuaj melanin.
Mechanism ntawm Action
(1) Kev khi rau Melanocortin Receptors
Tus yuam sij rau Melanotan-1 qhov ua tau zoo nyob hauv nws lub peev xwm los khi rau melanocortin receptors (MC1R). MC1R yog G protein-coupled receptor feem ntau qhia nyob rau saum npoo ntawm melanocytes. Thaum Melanotan-1 khi rau MC1R, nws ua rau muaj cov xwm txheej ntawm cov teeb liab intracellular transduction. Qhov kev khi no ua rau G protein ua ke rau MC1R, uas tig mus ua kom adenylate cyclase, ua rau muaj kev nce ntxiv hauv cov txheej txheem thib ob ntawm cov tub txib cyclic adenosine monophosphate (cAMP). Qhov nce hauv cAMP ntxiv ua kom muaj protein ntau kinase A (PKA), uas tswj cov kev qhia ntawm melanin synthesis-related genes los ntawm phosphorylating downstream transcription factor, microphthalmia-associated transcription factor (MITF).
Daim duab 2 Kev sib koom ua ke ntawm qhov kev hloov siab tshaj plaws hauv melanin ceev thiab lub hauv paus melanin ceev ntawm sab caj npab sab hauv hauv ITT cov tib neeg.
(2) Kev tswj cov noob qhia ntsig txog melanin synthesis
MITF yog ib qho tseem ceeb ntawm kev hloov pauv hauv cov txheej txheem melanin synthesis, muaj peev xwm los tswj cov kev qhia ntawm ntau cov noob encoding enzymes koom nrog hauv melanin synthesis, nrog tyrosinase yog qhov tseem ceeb tshaj plaws. Tyrosinase yog tus nqi-txheej enzyme hauv melanin synthesis, catalyzing maj mam hloov ntawm tyrosine mus rau dopaquinone, uas yog ces synthesized rau melanin. Melanotan-1 txhawb nqa MITF kev ua ub no, nce kev qhia ntawm tyrosinase thiab lwm yam melanin synthesis-related enzymes, yog li ceev cov txheej txheem melanin synthesis. Melanotan-1 kuj tseem tuaj yeem cuam tshuam qhov kev qhia ntawm lwm cov noob ntsig txog melanin synthesis, xws li dopa-colorin interconverting enzyme (DCT), thiab lwm yam. Cov enzymes no ua synergistically los txhawb melanin synthesis thiab tsub zuj zuj, thaum kawg ua rau cov tawv nqaij tawv xim.
(3) Synergistic teebmeem ntawm intracellular signaling pathways
Ntxiv rau qhov classic cAMP-PKA-MITF txoj kev taw qhia tau hais los saum toj no, Melanotan-1 kuj tseem tuaj yeem tswj hwm melanin synthesis los ntawm lwm txoj hauv kev hauv lub cev. Nws tuaj yeem cuam tshuam rau mitogen-activated protein kinase (MAPK) txoj kev taw qhia. Hauv melanocytes, MAPK teeb liab txoj hauv kev koom nrog kev tswj hwm ntau yam kev lom neeg xws li kev loj hlob ntawm tes, sib txawv, thiab kev ciaj sia. Melanotan-1 tuaj yeem qhib MAPK teeb liab txoj hauv kev los txhawb ntxiv melanocyte proliferation thiab melanin synthesis. PI3K-Akt txoj kev taw qhia kuj tseem tuaj yeem cuam tshuam nrog cov teebmeem ntawm Melanotan-1. Txoj kev no ua lub luag haujlwm tseem ceeb hauv kev loj hlob ntawm tes, kev ciaj sia, thiab kev tswj hwm cov metabolism, uas muaj peev xwm muab cov txheej txheem metabolic tsim nyog rau kev sib txuas ntawm melanin los ntawm kev tswj cov txheej txheem hauv cov txheej txheem metabolic.
Lub luag haujlwm hauv Kev Lag Luam Zoo Nkauj
(1) Txhawb daim tawv nqaij tanning
Manifestation ntawm Tanning teebmeem
Qhov tseem ceeb tshaj plaws ntawm cov tshuaj pleev ib ce ntawm Melanotan-1 yog nws lub peev xwm los txhawb cov tawv nqaij tanning. Cov kev tshawb fawb tau pom tias tom qab siv tshuaj Melanotan-1 los ntawm kev txhaj tshuaj subcutaneous lossis lwm txoj hauv kev tsim nyog ntawm kev tswj hwm, qhov tseem ceeb ntawm cov xim ntawm daim tawv nqaij tuaj yeem pom hauv cov ntsiab lus. Hauv kev tshawb fawb nrog cov txiv neej noj qab haus huv tuaj yeem pab dawb, kev txhaj tshuaj subcutaneous ntawm Melanotan-1 ntawm koob tshuaj 0.08-0.21 mg / kg tau noj tsis tu ncua rau 5 hnub dhau 2 lub lis piam (10 koob). Cov txiaj ntsig tau pom qhov tseem ceeb tanning hauv thaj chaw xws li hauv pliaj, caj npab, thiab caj dab ntawm cov khoom. Cov nyhuv tanning no tsis yog tshwm sim los ntawm UV-induced kev puas tsuaj tab sis yog los ntawm kev nce endogenous melanin synthesis, uas ua rau cov tawv nqaij ntau dua thiab ntuj.
Duration ntawm tanning nyhuv
Cov nyhuv tanning ntawm daim tawv nqaij raug ntxias los ntawm Melanotan-1 muaj qee qhov kev pheej hmoo. Cov kev tshawb fawb pom tias cov nyhuv tanning tau ncav cuag nws qhov siab tshaj li ib lub lis piam tom qab kev tswj hwm, thiab txawm tias peb lub lis piam tom qab ua tiav kaum koob tshuaj, cov tawv nqaij xim tseem ceeb dua ua ntej kho. Qhov no qhia tau hais tias Melanotan-1 tsis tsuas yog txhawb nqa melanin synthesis tab sis kuj hais tias melanin tsim los ntawm cov txheej txheem synthesis tuaj yeem khaws cia hauv daim tawv nqaij rau qee lub sijhawm, yog li txhawb nqa cov nyhuv tanning.
(2) Muaj peev xwm tiv thaiv daim tawv nqaij
UV tiv thaiv mechanism
Melanin yog ib qho tseem ceeb ntawm cov tawv nqaij tiv thaiv UV hluav taws xob. Los ntawm kev ua kom melanin synthesis, Melanotan-1 theoretically txhim kho daim tawv nqaij lub peev xwm nqus thiab tawg UV rays, yog li txo UV-induced kev puas tsuaj rau ntawm daim tawv nqaij. Melanin absorbs UV zog thiab hloov nws mus rau hauv thermal zog rau kev tso tawm, yog li txo qhov kev pheej hmoo ntawm UV-induced puas tsuaj rau lom macromolecules xws li DNA thiab cov proteins. Tsis tas li ntawd, melanin tuaj yeem tswj cov tawv nqaij tiv thaiv kab mob kom txo tau cov kab mob UV-induced inflammatory teb, ntxiv tiv thaiv daim tawv nqaij los ntawm kev puas tsuaj.
Cov ntaub ntawv tshawb fawb ntsig txog
Txawm hais tias kev tshawb fawb soj ntsuam ntawm kev tiv thaiv ntawm daim tawv nqaij ncaj qha ntawm Melanotan-1 tam sim no raug txwv, nws lub peev xwm tiv thaiv UV tuaj yeem raug txiav txim siab raws li lub cev kev ua haujlwm ntawm melanin thiab Melanotan-1 lub peev xwm los txhawb melanin synthesis. Qee qhov kev tshawb fawb hauv vitro tau pom tias melanocytes kho nrog Melanotan-1 qhia tau qis dua ntawm cov pa oxygen reactive (ROS) thiab txo qis apoptosis tom qab UV raug, qhia tias Melanotan-1 tuaj yeem txhim kho daim tawv nqaij kam rau UV hluav taws xob los ntawm boosting melanin synthesis.
(3) Lwm yam muaj feem cuam tshuam rau ntawm daim tawv nqaij
Txhim kho daim tawv nqaij zoo nkauj
Qee qhov qhia tias Melanotan-1 tuaj yeem cuam tshuam zoo rau ntawm daim tawv nqaij zoo nkauj. Ntxiv melanin synthesis tuaj yeem txhim kho cov metabolism hauv cellular, txhawb cov synthesis thiab rov ua dua tshiab ntawm collagen thiab elastic fibers. Hauv qee qhov kev soj ntsuam me me, qee cov neeg koom tau tshaj tawm tias lawv cov tawv nqaij ua kom tawv nqaij, elastic dua, thiab pom kev txhim kho hauv cov kab zoo thiab wrinkles tom qab siv Melanotan-1. Qhov no muaj feem xyuam rau cov kev cai ntawm daim tawv nqaij extracellular matrix metabolism los ntawm intracellular signaling pathways qhib thaum lub sij hawm melanin synthesis.
Txo cov tawv nqaij pigmentation
Qee cov kev tshawb fawb kuj tau pom tias Melanotan-1 yuav muaj qee yam cuam tshuam rau ntawm daim tawv nqaij pigmentation. Kev tsim ntawm daim tawv nqaij pigmentation feem ntau cuam tshuam nrog kev cuam tshuam ntawm melanin metabolism. Los ntawm kev tswj hwm melanin synthesis thiab kev faib tawm, Melanotan-1 tuaj yeem pab faib melanin ntau tusyees hauv daim tawv nqaij, yog li txo qhov pom ntawm pigmentation.
Kev siv hauv kev ua kom zoo nkauj
Tom qab txhaj tshuaj subcutaneously, Melanotan-1 yog absorbed los ntawm lub cev tag nrho, qhia txog tib yam bioavailability raws li kev txhaj tshuaj intravenously. Hauv kev tshawb fawb pharmacokinetic sib piv cov kev sib txawv ntawm kev tswj hwm, kev txhaj tshuaj subcutaneous ntawm Melanotan-1 ntawm koob tshuaj 0.08-0.21 mg / kg ua rau pom cov tshuaj ntau hauv plasma, nrog cov ntshav ib nrab ntawm lub neej ntawm 0.07-0.79 teev nyob rau theem nqus thiab 0.8-1.7 teev beta. Qhov zoo ntawm kev txhaj tshuaj subcutaneous suav nrog kev tswj hwm yooj yim thiab kev nqus tshuaj ruaj khov; Txawm li cas los xij, nws kuj muaj qee qhov kev txwv, xws li qhov mob hauv zos, liab liab, thiab lwm yam tshuaj tiv thaiv.
4. Kev sib piv nrog lwm txoj kev zoo nkauj
Kev sib piv nrog cov txheej txheem Sunbathing
Tsob tshuaj sunbathing yog ib txoj hauv kev kom ua tiav cov teebmeem ntawm daim tawv nqaij, tab sis txoj kev no muaj ntau qhov tsis zoo. Kev raug ultraviolet (UV) hluav taws xob ntev ua rau muaj kev pheej hmoo ntawm kev mob qog noj ntshav ntawm daim tawv nqaij, kev yees duab, thiab lwm yam mob, thaum tseem muaj peev xwm ua rau tshav ntuj, qhuav, thiab wrinkles. Melanotan-1-induced daim tawv nqaij tanning yog ua tiav los ntawm kev nce endogenous melanin synthesis, theoretically zam qhov kev puas tsuaj los ntawm kev raug UV ncaj qha. Txawm li cas los xij, txij li kev nyab xeeb ntawm Melanotan-1 tseem tsis tau tsim kom tiav, tam sim no nws tsis tuaj yeem hloov cov tsoos sunbathing raws li txoj kev nyab xeeb thiab txhim khu kev qha tanning.
Sib piv nrog Artificial Tanning khoom
Muaj qee cov khoom tsim tanning muaj nyob rau hauv kev ua lag luam, xws li tus kheej-tanning lotions, uas feem ntau hnov mob nrog cov amino acids ntawm daim tawv nqaij saum npoo los tsim cov xim zoo li tanned. Piv nrog rau Melanotan-1, cov khoom siv dag zog tanning ua rau ntawm daim tawv nqaij saum npoo, ua rau muaj kev cuam tshuam luv luv thiab yuav ua rau muaj teeb meem xws li xim tsis sib xws lossis tsis zoo. Melanotan-1, ntawm qhov tod tes, hloov cov xim ntawm daim tawv nqaij los ntawm kev tswj hwm melanin synthesis, uas muaj peev xwm ua kom muaj txiaj ntsig ntev dua thiab ntuj tsim.
Xaus
Raws li ib qho hluavtaws melanocyte-stimulating hormone peptide, Melanotan-1 feem ntau ua haujlwm los ntawm kev khi rau melanocyte-stimulating hormone receptors, ua kom intracellular signaling pathways, thiab tswj cov kev qhia ntawm cov noob ntsig txog melanin synthesis, yog li txhawb melanin synthesis. Nyob rau hauv cov nqe lus ntawm cov tshuaj pleev ib ce, nws zoo txhawb cov tawv nqaij tanning nrog ib tug tej yam degree ntawm persistence, thiab tej zaum kuj muaj peev xwm tiv thaiv tawv nqaij thiab lwm yam zoo cuam tshuam rau ntawm daim tawv nqaij tsos.
Qhov chaw
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[2] Fitzgerald LM, Fryer JL, Dwyer T, et al. Cov nyhuv ntawm MELANOTAN, [Nle(4), D-Phe(7)]-alpha-MSH, ntawm melanin synthesis hauv tib neeg nrog MC1R variant alleles[J]. Peptides, 2006,27(2):388-394.DOI:10.1016/j.peptides.2004.12.038.
[3] Ugwu S, Blanchard J, Dorr R, et al. Daim tawv nqaij pigmentation thiab pharmacokinetics ntawm melanotan-I hauv tib neeg [J]. Biopharmaceutics & Drug Disposition, 1997,18:259-269.DOI:10.1002/(SICI)1099-081X(199704)18:33.0.CO;2-X.
Cov khoom muaj rau kev tshawb fawb siv nkaus xwb:
