Na Cocer Peptides 
hashize iminsi 25
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.
Umubyibuho ukabije hamwe n’indwara ziterwa na metabolike byahindutse ikibazo cy’ubuzima rusange ku isi, bituma gushakisha ingamba zifatika kandi zifite akamaro. Mugihe imisemburo ikura yumuntu (hGH) yerekana ubushobozi bwo kuvura umubyibuho ukabije, impungenge z'umutekano zigabanya imikoreshereze yigihe kirekire. AOD9604, igice cya peptide kiva mu karere ka C-terminal ka HGH (Tyr-hGH177-191), byagaragaye ko gifite ibikorwa byo kugabanya amavuta ya HGH nta ngaruka mbi zabyo. Ubushakashatsi buherutse kwaguka ku mikorere yabwo, hamwe na antioxydeant na metabolike yingirakamaro igaragara nkibice byingenzi byubushakashatsi.
Igicapo 1 Umubyibuho ukabije ku bantu bakuru bo muri Amerika (imyaka 20–74).
1. Ingaruka za antioxydeant ya AOD9604
Isano iri hagati ya stress ya okiside n'indwara
Guhangayikishwa na Oxidative bivuga imiterere aho, iyo ibintu bitandukanye byangiza umubiri, umubiri utanga urugero rwinshi rwubwoko bwa ogisijeni (ROS) nubwoko bwa azote (RNS), bigatuma kwangirika kwa okiside kurenza ubushobozi bwumubiri bwo gukuraho ubwo bwoko. Uku kutaringaniza hagati ya sisitemu ya okiside na antioxydeant itera kwangirika kwinyama. Indwara nyinshi, zirimo n'indwara z'umutima-damura, diyabete, indwara zifata ubwonko, n'indwara y'umwijima idafite inzoga (NAFLD), ifitanye isano rya bugufi no guhagarika umutima. Muri izi ndwara zivuga, urugero rwa ROS rudasanzwe rwibasira biomolecules nka lipide, proteyine, na ADN, bigatuma imikorere mibi ya selile n'urupfu.
AOD9604 Uburyo bwa Antioxydeant Ibikorwa
AOD9604 ikora ingaruka zayo mugutunganya sisitemu ya antioxydeant antioxydeant. Superoxide dismutase (SOD), glutathione peroxidase (GPx), na catalase (CAT) ni imisemburo ikomeye ya antioxydants yo mu nda ishobora kwangiza ROS kandi ikagumana uburinganire bwa redox. AOD9604 irashobora kugenzura imvugo cyangwa ibikorwa byiyi misemburo ya antioxydeant, bityo bikazamura ubushobozi bwo kwirinda antioxydeant selile. Kurundi ruhande, AOD9604 irashobora kugira uruhare rutaziguye mugushakisha radicals yubuntu. Amatsinda amwe mumiterere yayo arashobora kuba afite ubushobozi bwo gufata ROS na RNS, bityo bikagabanya ibyangiritse kuri selile.
Mu bushakashatsi bwakoresheje urugero rwimbeba yindwara yumwijima idafite inzoga, kuvura hamwe na AOD9604 byatumye igabanuka ryinshi rya malondialdehyde (MDA) mubice byumwijima. MDA ni umusaruro wa lipide peroxidation, kandi kugabanuka kwayo byerekana kugabanuka kwa stress ya okiside. Ibikorwa bya SOD na GPx mu mwijima byiyongereye, byerekana ko AOD9604 ishobora kugabanya kwangirika kwa okiside mu kongera ibikorwa bya enzymes za antioxydeant. Ibi byerekana ko AOD9604 igira ingaruka nziza mugutezimbere umwijima wa okiside yumwijima, itanga ibimenyetso byubushakashatsi byerekana uburyo ikoreshwa mukuvura indwara zifitanye isano.
2. Ingaruka zo Gushyigikira Metabolic Ingaruka za AOD9604
Ingaruka kuri Lipid Metabolism
AOD9604 yerekana ingaruka zikomeye zoguhindura metabolism. Muburyo bwimbeba ifite umubyibuho ukabije, inshinge ndende ya intraperitoneal ya AOD9604 yatumye ibiro byumubiri bigabanuka. Ingaruka zishobora kuba zifitanye isano n'inzira ya ad-adrenergique, cyane cyane β (3) -yakira reseptor (β (3) -AR), reseptor ya lipolitike yibanze muri adipocytes. Nyuma yiminsi 14 yubuyobozi bwa AOD9604 mu mbeba zifite umubyibuho ukabije, urwego rwo kwerekana β (3) -AR RNA rwiyongereye, rugarura urwego β (3) -AR RNA rwahagaritswe mu mbeba zifite umubyibuho ukabije kurwego ugereranije n’izo mu mbeba zinanutse, bityo bigatuma lipolysis ikomeza kandi ikongerera imbaraga za lipolitike. Muri β (3) -AR imbeba ya knockout, gukoresha igihe kirekire AOD9604 yananiwe gutanga impinduka zingana nuburemere bwongera lipolysis nko mu mbeba zo kugenzura ubwoko, byerekana ko β (3) -AR igira uruhare runini mugutegeka AOD9604 kugenga metabolisme ya lipide. Mu bushakashatsi bukaze, AOD9604 iracyongera ingufu zikoreshwa hamwe na okiside yibinure muri β (3) -AR ya gene knockout imbeba, byerekana ko AOD9604 ishobora no guhindura metabolisme ya lipide ikoresheje izindi nzira.
Igishushanyo cya 2 Ingaruka yimiti imwe ya buri munsi ya intraperitoneal (ip) ya saline, AOD9604, cyangwa imisemburo ikura yumuntu (hGH) kumihindagurikire yuburemere bwumubiri kubagabo bananutse C57BL / 6J (A) cyangwa imbeba zifite umubyibuho ukabije (ob / ob) muminsi 14.
Ingaruka kuri carbhydrate metabolism
Kubijyanye na metabolisme ya karubone, AOD9604 itandukanye cyane na hGH. Igeragezwa rya Clinical ryerekana ko AOD9604 nta ngaruka igira kuri serumu IGF-1, yemeza hypothesis ko idakora binyuze muri IGF-1. Ibisubizo bivuye mu kizamini cyo kwihanganira glucose yo mu kanwa byerekanaga ko, bitandukanye na hGH, AOD9604 ntabwo bigira ingaruka mbi kuri metabolisme ya karubone. Ibi bivuze ko AOD9604 ishobora kugenga metabolisme ya lipide itabangamiye metabolisme isanzwe ya karubone, itanga inyungu idasanzwe mukuzamura imiterere ya metabolike.
Ingaruka kuri metabolism y'umwijima
Mu bushakashatsi bwakozwe ku mbeba zifite indwara y’umwijima idafite inzoga, AOD9604 ntabwo igira ingaruka gusa kuri metabolisme ya lipide ahubwo inagenga imiterere rusange yumwijima. Usibye kugabanya imihangayiko ya okiside, AOD9604 irashobora kunoza umwijima wo mu bwoko bwa hepatike igenga imiterere ya genes zijyanye na synthesis ya lipide, transport, na metabolism mu mwijima. Irashobora guhindura imvugo ya enzymes zingenzi nka synthase ya fatty acide (FAS) na acetyl-CoA carboxylase (ACC), kugabanya synthesis ya fatty acide mu mwijima, guteza aside irike β-okiside, bityo bikagabanya kwirundanya kwamavuta ya hepatike.
3. Ibishobora gukoreshwa mubikorwa bya AOD9604
Porogaramu mubyibushye hamwe nindwara zifitanye isano
Bitewe na AOD9604 ya antioxydants na metabolike yingirakamaro, ifite agaciro gakoreshwa mukuvura umubyibuho ukabije hamwe nindwara ziterwa na metabolike nka diyabete yo mu bwoko bwa 2 n'indwara y'umwijima idafite inzoga. Ku barwayi bafite umubyibuho ukabije, AOD9604 irashobora guteza imbere metabolisme ya lipide, kugabanya ibinure mu mubiri, no kunoza insuline, bityo igafasha mu kugenzura amaraso glucose. Ku barwayi bafite umwijima w’umwijima udafite inzoga, birashobora kugabanya umwijima wangiza umwijima no kugabanya metabolisme yumwijima, bishobora kuba ingamba nshya zo kunoza imikorere yumwijima no gutera indwara buhoro.
Porogaramu mu mirire ya siporo
Mu rwego rwimirire ya siporo, antioxydeant ya AOD9604 hamwe ningirakamaro ya metabolike nayo irashimishije. Mu myitozo ikaze cyane, abakinnyi bakora ROS nyinshi, bigatuma habaho kwangirika kwa okiside, mugihe ingufu za metabolisme zisaba kwiyongera. AOD9604 irashobora gufasha gukuraho ROS, kugabanya umunaniro wimitsi no kwangirika, mugihe utezimbere okiside yibinure yingufu, bityo bikongerera imbaraga kwihangana no kongera imbaraga. Nubwo AOD9604 yerekana antioxydants nziza na metabolike yingirakamaro, umutekano wacyo ningirakamaro cyane. Ubushakashatsi bwinshi bwasuzumye umutekano wa AOD9604. Mu bigeragezo bitandatu byateganijwe, impumyi ebyiri, bigenzurwa na platbo, AOD9604 nta ngaruka byagize ku rwego rwa serumu IGF-1, nta ngaruka mbi zagize kuri metabolisme ya karubone, kandi nta antibodiyide zirwanya AOD9604 zagaragaye. Nta bimenyetso byo kwikuramo cyangwa ibintu bibi cyane bijyanye no gufata AOD9604 byavuzwe. Mu bushakashatsi bw’uburozi bwa chronique bwakorewe mu mbeba n’inguge cynomolgus, ubuyobozi bwigihe kirekire bwo mu kanwa bwa AOD9604 nabwo bwerekanye umutekano wabwo muri rusange, nta kimenyetso cya genotoxicity.
Igicapo 3 Muri vitro kwangirika kwa AOD9604 muri plasma yimbeba mubushyuhe bwicyumba. Nyuma yiminota 56, peptide irandurwa burundu. Igice cya kabiri cyubuzima ni iminota 4. Kugaragara kwa AOD9604 amino-terminal yaciwe ibice (-xaa) irerekanwa.
4. Umwanzuro
AOD9604, nkigice cya peptide hamwe nibikorwa byihariye bibiri, bifasha muri antioxydeant na metabolike. Igikorwa cyacyo cya antioxydeant gifasha kugabanya kwangirika kwingirangingo zijyanye na stress ya okiside, mugihe ibikorwa byayo bifasha metabolike bigenga neza lipide, karubone, na metabolism yumwijima. Ibi bigira uruhare runini mu kuvura umubyibuho ukabije n'indwara ziterwa na metabolike, ndetse no mu mirire ya siporo.
Inkomoko
[1] Dehbashi M, Fathie M, Hosseini SRA, n'abandi. اثر هشت هفته تمرین استقامتی و تزریق قطعه لیپولیتیک هورمون رشد (AOD9604) بر آنزیمهای ربد و CK18 موشهای سوری القاء شده بل غذایی پر چرب ، 2021 [C]. https://api.semanticscholar.org/CorpusID:236556287
[2] EMIM, Kenley D L. Umutekano na Metabolisme ya AOD9604, Intungamubiri za Nutraceutical Intungamubiri zubuzima bwiza bwa metabolike [J]. Ikinyamakuru cya Endocrinology na Metabolism, 2014,4: 64-77. https://api.semanticscholar.org/CorpusID:67761634
[3] Stier H, Vos E, Kenley D L. Umutekano no kwihanganira Hexadecapeptide AOD9604 mubantu [J]. Ikinyamakuru cya Endocrinology na Metabolism, 2013,3: 7-15. https://api.semanticscholar.org/CorpusID:56559133
[4] Melnikova I, Umushahara D. Ubuvuzi bwo kurwanya umubyibuho ukabije [J]. Isuzuma rya Kamere Kuvumbura Ibiyobyabwenge, 2006,5 (5): 369-370.DOI: 10.1038 / nrd2037.
[5] Heffernan M, Impeshyi RJ, Thorburn A, n'abandi. Ingaruka za GH yumuntu nigice cya lipolytike (AOD9604) kuri metabolisme ya lipide nyuma yo kuvurwa karande ku mbeba zifite umubyibuho ukabije na beta (3) -AR imbeba yakomanze [J]. Endocrinology, 2001,142 (12): 5182-5189.DOI: 10.1210 / endo.142.12.8522.
Ibicuruzwa biboneka mubushakashatsi bukoreshwa gusa:
