Na Cocer Peptides 
ukwezi gushize
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 byemewe 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
Kuva yavumburwa mu 1999, ghrelin yagaragaye nkibintu byibandwaho mubushakashatsi mubumenyi bwubuzima kubera imikorere yihariye ya physiologiya ningaruka nini yibinyabuzima. Ghrelin igira uruhare runini mu kugenzura irekurwa ry’imisemburo ikura (GH) kandi igira uruhare mu bikorwa byinshi by’umubiri, harimo kuringaniza ingufu, kugenzura ubushake bwo kurya, imikorere ya gastrointestinal, homeostasis homeostasis, na neuroprotection.
Igishushanyo cya 1 imisemburo ya Ghrelin muburyo idakora (desacyl ghrelin) ihindurwa muburyo bukora (acyl ghrelin).
Imiterere nogukwirakwiza Ghrelin
(1) Imiterere
Ibigize imiti: Ghrelin ni polypeptide igizwe na acide 28 amine, hamwe nuburyo bwibanze bwerekana kubungabunga cyane amoko atandukanye. Mu bantu, aside amine ikurikirana ya ghrelin ni GSSFLSPEHQRVQQRKESKKPPAKLQPR. Umwihariko wacyo ni uguhindura octanoylation ku bisigarira bya serine kumwanya wa 3, ibyo bikaba ari ingenzi cyane kugirango ghrelin ihuze imisemburo ikura ya hormone ikura imisemburo (GHS-R) no gukoresha ibikorwa byibinyabuzima.
Isomers: Usibye na Ghrelin isanzwe ya octanoylated, hariho na Ghrelin deacetylated hamwe nabandi isomers. Nubwo Ghrelin ya deacetylated idafite ihinduka rya octanoylation kandi ikaba idafite ubushobozi bwo guhuza GHS-R hamwe cyane, ubushakashatsi bwerekanye ko bushobora kugira ingaruka ku binyabuzima binyuze mu zindi reseptor cyangwa uburyo butazwi.
(2) Ikwirakwizwa
Ikwirakwizwa ry'inyama: Ghrelin ikomatanyirizwa cyane kandi ikarekurwa na selile zisohora aside mu mitsi ya gastricique kandi ikanagaragarira mu ngingo nyinshi no mu ngingo, harimo amara mato, pancreas, hypothalamus, na glande ya pitoito. Mu nzira ya gastrointestinal, imvugo ya ghrelin igabanuka buhoro buhoro kuva mu gifu kugera mu mara mato. Muri sisitemu yo hagati yo hagati, ghrelin igaragara cyane mu turere nka arcuate nucleus na paraventricular nucleus ya hypothalamus, ifitanye isano rya bugufi no kugaburira ubushake bwo kurya, metabolism y'ingufu, no kugenzura neuroendocrine.
Guhindura ingirabuzimafatizo: Mu gifu, Ghrelin igaragarira cyane cyane mu ngirabuzimafatizo ya endocrine ya mucosa yo mu gifu, ishobora kumenya imirire iri mu nzira ya gastrointestinal kandi ikohereza ibimenyetso muri sisitemu yo hagati y’imitsi ikoresheje ururenda rwa Ghrelin. Muri glande ya pitoito, Ghrelin irashobora gukora muburyo butaziguye imisemburo ikura kugirango igabanye imisemburo ikura.
Uburyo bwibikorwa byo Gukura Hormone-Kurekura Peptide
(1) Guhambira ababyakira
Inzira yerekana ibimenyetso bya GHS-R: Ingaruka yibanze yibinyabuzima ya Ghrelin igerwaho hifashishijwe guhuza imisemburo ikura ya hormone ikura 1a (GHS-R1a). GHS-R1a ni poroteyine G ihujwe na reseptor ikwirakwizwa cyane muri glande ya pitoito, hypothalamus, nizindi ngingo zose. Iyo ghrelin ihujwe na GHS-R1a, ghrelin ikora proteine za G, nazo zigakora fosifolipase C (PLC) -inositol trisphosphate (IP3) -calcium ion (Ca⊃2;
Uburyo butari GHS-R bwahujwe: Usibye GHS-R1a, ubushakashatsi bwerekanye ko ghrelin ishobora no kugira ingaruka ku binyabuzima binyuze mu mikoranire n’abandi bakira cyangwa poroteyine za membrane.
Igishushanyo 2 Ghrelin ikora ingaruka zayo muri hypothalamus ikoresheje inzira eshatu zitandukanye.
(2) Kugena imvugo ya gene
Hypothalamic-pituitar axis ifitanye isano na gen: Ghrelin irashobora kugenga imvugo ya genes nyinshi muri hypothalamic-pituitar axis. Ku rwego rwa pitoito, ghrelin irashobora kugenzura iyimurwa rya hormone ikura, igatera synthesis hamwe no kurekura imisemburo ikura. Muri hypothalamus, ghrelin irashobora kugira uruhare mu kwerekana imisemburo ikura ya hormone ikura (GHRH) na somatostatine (SS), igenga mu buryo butaziguye imisemburo ikura ihindura imisemburo ya GHRH na SS. By'umwihariko, ghrelin irashobora gukurura ururenda rwa GHRH mugihe ibuza SS gusohora, bityo igahuza imbaraga zo gusohora imisemburo ikura.
Ingirabuzimafatizo zijyanye n'ingufu: Muri tipusi ya adipose n'umwijima, ghrelin igenga imiterere ya genes zijyanye na metabolism. Kurugero, ghrelin irashobora kugenzura imvugo ya peroxisome prolifator-ikora reseptor γ (PPARγ), iteza imbere itandukaniro rya adipocyte na lipogenez; icyarimwe, mu mwijima, ghrelin igenga imiterere ya genes zijyanye na gluconeogenez, bigira ingaruka kuri homeostasis ya glucose yamaraso.
Ingaruka za physiologique zo gukura imisemburo ikura peptide
(1) Guteza imbere imisemburo ikura
Igikorwa kiziguye kuri glande ya pitoito: Ghrelin nikintu gikomeye cyo gukura imisemburo ikura imisemburo ikora mumasemburo ya hormone ikura mumyanya ndangagitsina ya pitoito, iteza imbere no gusohora imisemburo ikura ikoresheje inzira ya GHS-R1a. Ugereranije na hormone ikura imisemburo irekura (GHRH), ghrelin itera imisemburo ikura vuba, kandi byombi bigira ingaruka. Mugihe cyimiterere yumubiri, ghrelin, GHRH, na somatostatine bigenga hamwe bigenga imisemburo ya pulsatile yimisemburo ikura, bikomeza imisemburo isanzwe ikura.
Ingaruka ku mikurire: Imisemburo ikura igira uruhare runini mugutezimbere imikurire niterambere. Ghrelin igira uruhare rutaziguye mu mikurire itera imisemburo ikura. Mugihe cyubwana nubwangavu, gusohora kwa Ghrelin ningirakamaro mubikorwa nko gukura kw'amagufwa no gukura kw'imitsi. Ku barwayi bafite imisemburo ikura, imisemburo ya ghrelin iba mike. Imiyoborere idasanzwe ya ghrelin cyangwa ibisa nayo irashobora kongera neza imisemburo ikura kandi igatera imbere no gutera imbere.
(2) Kugena ingufu za Metabolism
Amabwiriza yo Kurya: Ghrelin, izwi nka 'imisemburo yinzara, ' ni molekile yerekana ibimenyetso bigenga ubushake bwo kurya. Muri arcuate nucleus ya hypothalamus, ghrelin ihuza reseptor ya GHS-R1a kuri neuropeptide Y (NPY) / poroteyine ifitanye isano na poroteyine (AgRP), itera irekurwa rya NPY na AgRP, bityo bikongerera ubushake bwo kurya no guteza imbere ibiryo. Ghrelin kandi igira uruhare rutaziguye mu kurya mu kugenzura imikorere ya neurone ya corticotropine irekura imisemburo (CRH) muri nucleus ya paraventricular ya hypothalamus. Mugihe cyo kwiyiriza ubusa, ghrelin irazamuka, itera inzara; nyuma yo kurya, ghrelin igabanuka vuba, byongera ibyuzuye.
Kuringaniza ingufu zingufu: Ghrelin nayo igira uruhare mugutunganya metabolism yingufu, ikomeza imbaraga zumubiri. Ghrelin itera lipolysis, ikongera aside irike, kandi ikongerera imbaraga umubiri. Ghrelin ibuza gusohora kwa insuline, igabanya gufata ingirabuzimafatizo no gukoresha glucose, kandi ikazamura urugero rwa glucose mu maraso, igaha umubiri andi masoko y’ingufu. Kugaragaza cyane karande ya ghrelin irashobora gutuma umuntu afata ingufu nyinshi, kwirundanya amavuta, hamwe nindwara ziterwa na metabolike nkumubyibuho ukabije.
(3) Ingaruka kumikorere ya gastrointestinal
Isohora rya aside Gastricike hamwe na moteri ya gastrointestinal: Mu nzira ya gastrointestinal, ghrelin igira uruhare runini mugutegeka mugusohora aside gastricike no kwihuta kwa gastrointestinal. Ghrelin itera ingirabuzimafatizo zo mu nda kugira ngo isohore aside gastricike, igenga ibidukikije bya aside iri mu gifu, ifasha mu igogorwa ry'ibiryo no kuyakira. Ghrelin iteza imbere gastrointestinal peristalsis, ikongera imbaraga zigenda mu nzira ya gastrointestinal no kwihutisha gusiba ibiryo biva mu nzira. Mu ndwara zimwe na zimwe zifata gastrointestinal, nka dyspepsia ikora na gastroparesis, urugero rwa Ghrelin rudasanzwe rushobora gutera ihungabana mu gusohora aside gastricike no kugenda kwa gastrointestinal.
Kurinda Mucosa Gastrointestinal: Ghrelin igira ingaruka zo gukingira mucosa gastrointestinal. Itera ikwirakwizwa no gusana ingirabuzimafatizo zo mu nda, byongera imikorere ya barrière, kandi ikarinda ibyangizwa n’ibintu byangiza nka aside gastric na Helicobacter pylori. Mubyitegererezo byindwara nkibisebe byo munda hamwe n ibisebe byo munda, imiyoborere idasanzwe ya ghrelin yihutisha gukira ibisebe kandi bigabanya urugero rwangirika.
(4) Amabwiriza ya sisitemu yumutima
Imikorere yumutima: Ghrelin igaragara cyane mumutima kandi igira uruhare runini mugikorwa cyumutima. Ghrelin yongerera myocardial kwandura, ikongera umutima, kandi igateza imbere imikorere yo kuvoma umutima. Muri myocardial ischemia-reperfusion moderi yimvune, ghrelin igabanya myocardial selile apoptose na necrosis, igabanya ubunini bwa infarct, kandi ikagira ingaruka kumutima. Uburyo bwabwo bushobora kuba bufitanye isano no gukora inzira yo kubaho kwizima ryerekana inzira, nka fosifinositide 3-kinase (PI3K) / protein kinase B (Akt) yerekana inzira.
Amabwiriza agenga umuvuduko w'amaraso: Ghrelin igenga umuvuduko w'amaraso kandi ikomeza umuvuduko w'amaraso uhamye. Ikora ku ngirabuzimafatizo zorohereza imitsi kugira ngo ibuze ingaruka ziterwa na vasoconstrictive nka angiotensin II, itera vasodilasiyo, igabanya imitsi y'amaraso ya peripheri, bityo bikagabanya umuvuduko w'amaraso. Ghrelin irabuza kandi kwerekana imiterere ya molekile ya endoteliyale ingirabuzimafatizo, kugabanya kugabanuka no kwinjira mu ngirabuzimafatizo, bikagira ingaruka zo gukingira imitsi, kandi bikabuza iterambere rya aterosklerose.
(5) Ingaruka za Neuroprotective
Kubaho kwa Neuronal no gukwirakwira: Muri sisitemu y'imitsi, ghrelin igira ingaruka zo kurinda neuron. Itera ikwirakwizwa no gutandukanya ingirabuzimafatizo ngengabuzima, ikongera umubare wa neuron, kandi igakomeza iterambere risanzwe n'imikorere ya sisitemu y'imitsi. Mubyitegererezo byindwara zifata ubwonko nkindwara ya Alzheimer nindwara ya Parkinson, ghrelin irashobora kubuza apoptose ya neuronal, kugabanya ibisubizo bya neuroinflammatory, no kunoza imikorere yubwenge na moteri. Uburyo bwabwo bwa neuroprotective burashobora kuba bujyanye no kugenzura ibibazo biterwa no guhagarika umutima, guhagarika inzira zerekana ibimenyetso bya apoptose, no guteza imbere irekurwa rya neurotransmitter.
Amabwiriza ya Neuroendocrine: Nkibintu bigenga neuroendocrine, Ghrelin agira uruhare mugutunganya imikorere ya hypothalamic-pituitar-adrenal axis (axis ya HPA). Mugihe cyimihangayiko, urugero rwa ghrelin rwinshi rubuza gukora cyane umurongo wa HPA, kugabanya imisemburo ya corticosteroid bityo bikagabanya kwangirika kwatewe numubiri. Byongeye kandi, ghrelin igenga hypothalamic-pitoitar-tiroyide (HPT axis) hamwe na hypothalamic-pituitar-gonadal axis (HPG axis), ikomeza homeostasis ya sisitemu ya neuroendocrine.
(6) Izindi ngaruka zifatika
Kugena ubudahangarwa bw'umubiri: Ghrelin nayo igira uruhare muri sisitemu yumubiri. Irashobora kugenga imikorere ya selile yumubiri, igatera ikwirakwizwa rya lymphocytes no gutandukanya lymphocytes, kandi ikongerera imbaraga umubiri imbaraga zo gukingira umubiri. Muri leta zitera umuriro, ghrelin irashobora kubuza irekurwa rya cytokine ikongora, nka feri ya necrosis yibibyimba-α (TNF-α) na interleukin-6 (IL-6), bityo bikagabanya ibisubizo byumuriro kandi bikagira ingaruka zubudahangarwa no kurwanya indwara.
Amabwiriza yo Guhindura Amagufwa: Ghrelin igira ingaruka zoguhindura amagufwa. Itera ikwirakwizwa no gutandukanya osteoblasts, ikabuza ibikorwa bya osteoclasts, bityo ikongera amagufwa kandi igatera amagufwa. Ku barwayi barwaye osteoporose, urugero rwa ghrelin rugabanuka, byerekana ko ghrelin ishobora kuba ifitanye isano no gukura kwa osteoporose. Imiyoborere idasanzwe ya ghrelin cyangwa ibisa nayo irashobora gutanga ingamba nshya zo kuvura osteoporose.
Porogaramu yo Gukura Hormone-Kurekura Peptide
(1) Ubuvuzi bwa Clinical
Gukura kwa Hormone Kubura: Kubarwayi bafite imisemburo ikura, Ghrelin nibindi bisa birashobora kuba imiti ivura. Mugukangurira gusohora imisemburo ikura, biteza imbere no gutera imbere kubarwayi. Ugereranije nubuvuzi gakondo bwo gusimbuza imisemburo, Ghrelin nibindi bisa bitanga umutekano mwiza no kwihanganira, kandi birashobora guteza imbere gukura muburyo bukwiye bwa physiologique muguhindura imisemburo ya hormone ikura.
Igicapo 3 Amabwiriza ya Endocrine ya GH hamwe no gukumira imiti.
Indwara za Metabolic
Umubyibuho ukabije na Diyabete: Mu kuvura umubyibuho ukabije, nubwo Ghrelin yitwa 'imisemburo y’inzara, ' igenga urwego rwa Ghrelin cyangwa inzira zayo zerekana ibimenyetso bishobora guhindura imbaraga za metabolisme, bikagabanya ubushake bwo kurya, kandi bikagabanuka. Gutezimbere anteptoriste ya Ghrelin kugirango ibuze Ghrelin guhuza reseptors irashobora guhagarika ubushake no kugabanya ibiryo. Ku barwayi ba diyabete, Ghrelin irashobora kugira ingaruka nziza ku maraso glucose ikoresheje uburyo nko kugenzura imisemburo ya insuline no kunoza insuline. Ubuyobozi budasanzwe bwa Ghrelin butezimbere glucose yamaraso hamwe no kumva insuline mu mbeba za diyabete, bitanga ubumenyi bushya bwo kuvura diyabete.
Indwara ya metabolike: Indwara ya metabolike ni itsinda ryindwara zirangwa n'umubyibuho ukabije, hypertension, hyperglycemia, na dyslipidemia. Bitewe n'uruhare rwayo mu mikorere ya metabolisme no kugenzura imitima n'imitsi, ghrelin irashobora kuba intego yo kuvura syndrome de metabolike. Mugutegeka urugero rwa ghrelin, birashoboka ko icyarimwe icyarimwe cyo kunoza icyarimwe ibimenyetso byinshi byindwara ziterwa na metabolike kubarwayi barwaye syndrome de metabolike, nko kugabanya ibiro, kugabanya umuvuduko wamaraso, no kunoza glucose yamaraso na lipide idasanzwe.
Indwara zo munda:
Dyspepsia ikora na gastroparesis: Kubarwayi bafite dyspepsia ikora na gastroparesis, ghrelin nibindi bisa nabyo birashobora kunoza ibimenyetso byigifu kandi byihutisha gusohora gastrica biteza imbere umuvuduko wa gastrointestinal no kongera aside irike. Gukoresha ibigereranyo bya ghrelin birashobora kugabanya neza ibimenyetso nkububabare bwo munda bwo hejuru no kubyimba kubarwayi barwaye dyspepsia ikora, bityo bakazamura imibereho yabo.
Ibisebe byo mu gifu: Bitewe n'ingaruka za Ghrelin zirinda mucosa gastrointestinal, irashobora gutera gukira ibisebe bityo ikaba ifite agaciro gakoreshwa mukuvura ibisebe byo munda. Imiyoborere idasanzwe ya Ghrelin cyangwa ibisa nayo irashobora kwihutisha gahunda yo gusana ibisebe no kugabanya ibisebe.
Indwara z'umutima n'imitsi:
Indwara ya Myocardial ischemia-reperfusion: Mu kuvura imvune ya myocardial ischemia-reperfusion, Ghrelin, bitewe n'ingaruka zayo z'umutima, itanga amasezerano nk'umuti mushya wo kuvura. Mugukoresha Ghrelin cyangwa ibisa nayo mbere cyangwa mugihe cya myocardial ischemia-reperfusion, irashobora kugabanya kwangirika kwingirabuzimafatizo, kugabanya ingano ya infarct, no kunoza imikorere yumutima. Ubushakashatsi bw’inyamaswa n’ibisubizo by’amavuriro byagaragaje umusaruro ushimishije, bitanga ingamba nshya zo kuvura imvune ya myocardial ischemia-reperfusion.
Kunanirwa k'umutima: Ku barwayi bafite ikibazo cyo kunanirwa k'umutima, urugero rwa Ghrelin akenshi rugabanuka kandi bifitanye isano n'uburemere bwo kunanirwa k'umutima. Kwiyongera hamwe na Ghrelin cyangwa ibisa nayo birashobora kunoza imikorere yumutima kubarwayi bananirwa kumutima bongerera ubwonko bwa myocardial, kunoza imitekerereze yumutima wumutima, no guhagarika apoptose selile myocardial, bityo bikazamura imibereho yabarwayi nubuzima bwabo.
Indwara zifata ubwonko:
Indwara ya Alzheimer n'indwara ya Parkinson: Urebye ingaruka za neuroprotective ya Ghrelin, ifite agaciro gakoreshwa mu kuvura indwara zifata ubwonko nk'indwara ya Alzheimer n'indwara ya Parkinson. Mugukoresha Ghrelin cyangwa ibisa nayo, irashobora kubuza apoptose ya neuronal, kugabanya ibisubizo bya neuroinflammatory, no kunoza imikorere yabarwayi na moteri.
Gukomeretsa Ubwonko no Guhahamuka Ubwonko: Mu bikomere bikabije by’imitsi nko mu bwonko no gukomeretsa ubwonko bw’ubwonko, Ghrelin ashobora kugira ingaruka zo mu bwonko binyuze mu buryo bukubiyemo kugabanya kwangirika kw’imitsi no guteza imbere imitekerereze mishya. Ubushakashatsi bwerekanye ko mu buryo bw’inyamanswa zerekana ubwonko cyangwa gukomeretsa ubwonko, gukoresha Ghrelin bishobora kugabanya ingano ya infarct cyangwa kugabanya ubwonko bwangirika, bityo bikazamura imikorere y’imitsi. Ghrelin irashobora kuba nk'ubuvuzi bufatika bwo gukomeretsa ubwonko no gukomeretsa ubwonko, bikarushaho guteza imbere abarwayi.
Umwanzuro
Nka peptide ikora cyane, peptide, Ghrelin igira uruhare runini mubikorwa bitandukanye byumubiri, harimo gukura niterambere, metabolisme yingufu, imikorere ya gastrointestinal, sisitemu yumutima nimiyoboro y'amaraso homeostasis, na neuroprotection.
Inkomoko
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[2] Ibrahim A M. Ghrelin - Imikorere ya Physiologique no kugenga [J]. Eur Endocrinol, 2015,11 (2): 90-95.DOI: 10.17925 / EE.2015.11.02.90.
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