Los ntawm Cocer Peptides 
15 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.
Kev Loj Hlob Hormone (GH) ua lub luag haujlwm tseem ceeb hauv ntau cov txheej txheem physiological, suav nrog kev loj hlob, kev loj hlob, thiab kev tswj hwm metabolic hauv cov kab mob nyob. Nws cov secretion yog tswj tau zoo los ntawm cov txheej txheem neuroendocrine nyuaj, thiab Kev Loj Hlob Hormone-Releasing Peptides (GHRPs) yog ib chav kawm ntawm cov khoom uas txhawb kev loj hlob hormone secretion, nyiam cov neeg tshawb fawb tseem ceeb. Ipamorelin, ua ib tug tswv cuab ntawm tsev neeg GHRP, sawv tawm rau nws cov qauv tshwj xeeb thiab muaj peev xwm hais tau los txhawb kev loj hlob hormone secretion.
Los ntawm cov qauv tsim tshuaj, Ipamorelin yog ib qho hluavtaws pentapeptide. Cov qauv no ua rau nws muaj kev sib raug zoo siab rau Kev Loj Hlob Hormone-Tshuaj Peptide Receptor (GHRP-R), ua kom nws ua haujlwm zoo rau cov receptor thiab pib ua ntau txoj hauv kev taw qhia intracellular, yog li txhawb kev loj hlob hormone secretion.
Piv nrog rau Kev Loj Hlob Hormone-Tshuaj Hormone (GHRH), Ipamorelin muaj ntau yam zoo. GHRH feem ntau ua rau GHRH receptors nyob rau saum npoo ntawm kev loj hlob hormone hlwb nyob rau hauv lub anterior pituitary caj pas los txhawb lub synthesis thiab tso tawm ntawm kev loj hlob hormone. Ipamorelin tsis tsuas yog ua ncaj qha rau ntawm lub caj pas pituitary tab sis kuj tseem tswj hwm kev loj hlob hormone secretion los ntawm kev ua haujlwm ntawm hypothalamus thiab lwm thaj chaw, muab ntau hom kev ua haujlwm. Ipamorelin nthuav tawm kev xaiv ntau dua hauv kev txhawb nqa kev loj hlob hormone secretion, nthuav tawm cov txiaj ntsig zoo ntawm kev loj hlob hormone secretion thaum muaj kev cuam tshuam tsawg kawg ntawm cov ntshav ntshav ntawm lwm cov tshuaj hormones pituitary xws li follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), thiab thyroid-stimulating hormone (TSH).
Hauv kev sim tsiaj, Ipamorelin tau pom tias muaj txiaj ntsig zoo hauv kev txhawb kev loj hlob hormone tso tawm thoob plaws ntau hom tsiaj, suav nrog nas, npua, yaj, thiab dev. Hauv kev sim nas, tom qab kev tswj hwm ntawm Ipamorelin, kev nce qib hauv cov ntshav plasma loj hlob hormone tau pom, pom muaj kev sib raug zoo ntawm koob tshuaj. Qhov no qhia tau hais tias Ipamorelin tuaj yeem tswj hwm kev loj hlob hormone secretion, muab pov thawj kev sim muaj zog rau nws cov kev siv peev xwm hauv kev txhim kho tsiaj kev loj hlob thiab kho cov kab mob.
Daim duab 1 Table 1 Cov qauv-kev sib raug zoo ntawm qee qhov tshiab pentapeptides ntawm GH tso tawm ntawm nas pituitary hlwb hauv vitro - kev sib piv nrog GHRP-1, GHRP-2, GHRP-6, thiab GHRH. Cov txiaj ntsig tau pom raws li txhais tau tias ± SEM (n = 3–6 kev sim cais).
Mechanism ntawm kev txiav txim ntawm Ipamorelin txhawb kev loj hlob hormone secretion
Kev sib cuam tshuam nrog kev loj hlob hormone-tso peptide receptor
Thawj kauj ruam tseem ceeb hauv Ipamorelin lub luag haujlwm hauv kev txhawb kev loj hlob hormone secretion yog nws qhov tshwj xeeb khi rau kev loj hlob hormone-tso peptide receptor (GHRP-R). GHRP-R belongs rau G protein-coupled receptor superfamily thiab yog dav faib nyob rau hauv lub anterior pituitary, lub hypothalamus, thiab lwm yam peripheral ntaub so ntswg. Cov qauv pentapeptide ntawm Ipamorelin ua rau nws muaj kev cuam tshuam nrog lub hnab tsho ligand-binding ntawm GHRP-R, ua rau muaj kev hloov pauv hauv cov receptor. Qhov kev hloov pauv no ua raws li 'hloov' los pib hloov cov teeb liab intracellular, tso cai rau GHRP-R cuam tshuam nrog thiab qhib cov kab hauv qab G.
GHRP-R activated txhawb guanosine nucleotide pauv hauv G protein α subunit ua ke rau nws, nrog GDP raug hloov los ntawm GTP, ua rau G protein α subunit dissociate los ntawm G protein βγ dimer. Lub dissociated G protein α subunit thiab G protein βγ dimer tuaj yeem ua kom muaj kev sib txawv ntawm cov kab hluav taws xob hauv qab, ua rau muaj kev cuam tshuam ntawm cov kab mob hauv lub cev, thaum kawg ua rau muaj kev loj hlob hormone secretion.
CJC-1295, raws li ib tug synthetic loj hlob hormone analog, pab nyob rau hauv yuag poob, nqaij li, rejuvenation ntawm daim tawv nqaij, pw txhim kho, thiab kho qhov txhab. Ipamorelin yog ib qho hluavtaws pentapeptide uas muaj nyob rau hauv chav kawm ntawm kev loj hlob hormone-tso peptides (secretagogues). Nws txhawb kev tso tawm ntawm cov tshuaj hormones loj hlob thiab cuam tshuam ntau yam kev ua haujlwm ntawm lub cev, suav nrog kev ua kom lub plab zom mov, txhim kho cov tsos mob ntawm plab hnyuv txhaws, txhawb kev tsim cov tshuaj insulin, thiab tiv thaiv cov teebmeem catabolic ntawm glucocorticoids ntawm cov leeg pob txha thiab pob txha. Kev kawm txog kev sib koom ua ke ntawm ob lub tebchaw no tuaj yeem ua rau muaj kev cuam tshuam tshiab hauv kev noj qab haus huv, tshuaj kis las, thiab kev kho mob ntsig txog.
Daim duab 2 Plasma GH qib piv rau lub sijhawm hauv swine tom qab iv kev tswj hwm ntawm ntau koob tshuaj ipamorelin.
Activation ntawm intracellular teeb liab transduction txoj kev
Phospholipase C - protein kinase C pathway (PLC - PKC txoj kev): Lub tshuab ua haujlwm G protein α subunit tuaj yeem ua kom phospholipase C (PLC), uas hydrolyzes phosphatidylinositol-4,5-bisphosphate (PIP2) ntawm cov cell membrane rau hauv ob qho tseem ceeb thib ob xa xov: inositol-1IPs, phosphatidylinositol-1IPs. diacylglycerol (DAG). IP3 diffuses mus rau hauv cytoplasm, khi rau IP3 receptors ntawm endoplasmic reticulum, thiab txhawb kev tso tawm ntawm calcium ions (Ca 2+ ) los ntawm endoplasmic reticulum, ua rau muaj kev nce sai hauv intracellular Ca 2+ concentration. DAG tseem nyob ntawm cov cell membrane thiab ua kom muaj protein ntau kinase C (PKC). PKC tuaj yeem tswj hwm qhov kev qhia ntawm cov noob muaj feem cuam tshuam los ntawm phosphorylating cov txheej txheem ntawm cov khoom siv qis qis, xws li cov khoom hloov pauv, yog li txhawb kev sib txuas thiab tso tawm ntawm cov tshuaj hormones loj hlob. Qhov siab intracellular Ca⊃2;⁺ concentration kuj tuaj yeem ua ncaj qha rau ntawm cov hlab ntsha hauv lub cev los txhawb kev tso tawm cov tshuaj hormones loj hlob.
Mitogen-activated protein kinase txoj kev (MAPK txoj kev): Ntxiv nrog rau txoj kev PLC-PKC, Ipamorelin qhib txoj kev mitogen-activated protein kinase tom qab ua kom GHRP-R txhawb kev loj hlob hormone secretion. G protein βγ dimer activates guanine nucleotide exchange factor (GEF), uas txhawb kev hloov dua siab tshiab ntawm GDP khi rau Ras protein rau GTP, yog li activating Ras protein. Activated Ras protein ntxiv activates Raf protein, uas phosphorylates thiab activates mitogen-activated protein kinase kinase (MEK). MEK yog tom qab ntawd phosphorylated thiab ua kom lub zog ntxiv ntawm cov teeb liab tswj kinase (ERK). Tom qab nkag mus rau hauv lub cell nucleus, ERK phosphorylates ib tug series ntawm transcription yam tseem ceeb, xws li Elk-1, tswj cov kev qhia ntawm noob muaj feem xyuam rau txoj kev loj hlob hormone synthesis thiab secretion, yog li txhawb kev tsim thiab tso tawm ntawm kev loj hlob hormone.
Kev tswj hwm ntawm hypothalamic-pituitary axis
Lub hypothalamic-pituitary axis plays lub luag haujlwm tseem ceeb hauv kev tswj hwm kev loj hlob hormone secretion. Ipamorelin tsis tsuas yog ua ncaj qha rau kev loj hlob hormone hlwb nyob rau hauv lub anterior pituitary caj pas los txhawb txoj kev loj hlob hormone secretion tab sis kuj tsis ncaj qha cuam tshuam kev loj hlob hormone tso tawm los ntawm kev tswj ntawm lub hypothalamus. GHRH thiab somatostatin (SST) secreted los ntawm hypothalamus muaj kev txhawb nqa thiab inhibitory cuam tshuam rau kev loj hlob hormone secretion, feem. Ipamorelin tuaj yeem tswj hwm txoj kev loj hlob hormone secretion los ntawm kev hloov cov synthesis thiab tso tawm ntawm GHRH thiab SST hauv hypothalamic neurons. Ipamorelin tuaj yeem cuam tshuam kev ua haujlwm ntawm SST neurons hauv hypothalamus, txo qis SST tso tawm, yog li txo qis cov nyhuv inhibitory ntawm SST ntawm kev loj hlob hormone secretion. Ipamorelin kuj tseem tuaj yeem txhim kho qhov excitability ntawm GHRH neurons, txhawb GHRH tso tawm, thiab ntxiv dag zog rau kev loj hlob hormone secretion. Qhov kev tswj hwm ob txoj cai no rau ntawm hypothalamic-pituitary axis ua rau Ipamorelin tswj kev loj hlob hormone secretion theem.
Lub luag haujlwm ntawm Ipamorelin hauv kev txhawb nqa kev loj hlob hormone secretion
Txhawb kev loj hlob thiab kev loj hlob
Thaum lub sijhawm tsiaj loj hlob thiab kev loj hlob, kev loj hlob hormone plays lub luag haujlwm tseem ceeb ntawm kev tswj hwm, thiab Ipamorelin cuam tshuam rau tsiaj loj hlob thiab kev loj hlob los ntawm kev txhawb nqa kev loj hlob hormone secretion. Hauv cov tsiaj hluas, kev siv Ipamorelin ua rau muaj kev loj hlob ntau. Noj cov nas ua piv txwv, tom qab noj cov tshuaj Ipamorelin uas tsim nyog, cov nas pom muaj qhov hnyav nce ntxiv, txhim kho kev loj hlob thiab kev sib txawv ntawm cov pob txha loj hlob daim hlau, thiab nce cov pob txha ntev. Qhov no tuaj yeem raug ntaus nqi los ntawm qhov tseeb tias kev loj hlob hormone txhawb kev tsim cov tshuaj insulin zoo li kev loj hlob zoo-1 (IGF-1) hauv cov ntaub so ntswg xws li daim siab. IGF-1 circulates los ntawm cov hlab ntsha mus rau cov ntaub so ntswg zoo li cov pob txha, txhawb kev loj hlob thiab kev sib txawv ntawm chondrocytes, yog li pab txhawb cov pob txha loj hlob. Ipamorelin txhawb kev loj hlob hormone secretion, indirectly nce IGF-1 ntau lawm, yog li ua kom cov pob txha loj hlob thiab kev loj hlob.
Ipamorelin kuj txhawb kev loj hlob ntawm cov leeg. Kev loj hlob hormone txhawb kev tsim cov protein, inhibits protein ntau, thiab ua kom cov leeg nqaij. Hauv kev sim tsiaj, tom qab siv Ipamorelin, cov tsiaj tau nthuav tawm cov leeg nqaij tuab thiab txhim kho cov leeg nqaij.
Regulatory cuam tshuam rau cov metabolism
Glucose metabolism regulation: Ipamorelin txhawb kev loj hlob hormone secretion, exerting ib tug tej yam kev cai ntawm cov piam thaj metabolism. Kev loj hlob hormone muaj ob lub luag haujlwm hauv cov piam thaj metabolism. Nyob rau theem ntawm lub cev, kev loj hlob hormone txhawb kev tsim cov tshuaj insulin, txhawb nqa cov piam thaj thiab siv, thiab txo cov ntshav qabzib. Ntawm qhov siab siab, cov tshuaj hormones loj hlob tuaj yeem ua rau muaj kev tiv thaiv insulin, inhibiting peripheral cov ntaub so ntswg thiab siv, yog li ua rau cov ntshav qabzib nce ntxiv. Ipamorelin tsis ncaj qha cuam tshuam cov piam thaj hauv cov metabolism los ntawm kev tswj hwm kev loj hlob hormone secretion. Hauv cov tsiaj ib txwm muaj, cov koob tshuaj uas tsim nyog ntawm Ipamorelin tuaj yeem tswj cov ntshav qabzib nyob rau hauv ib qho chaw ruaj khov, uas tuaj yeem raug ntaus nqi rau nws txoj kev loj hlob hormone secretion, uas nyob rau hauv lem stimulates insulin tso tawm rau qee qhov, yog li tswj cov ntshav qabzib. Hauv cov qauv tsiaj mob ntshav qab zib, cov teebmeem ntawm Ipamorelin yog qhov nyuaj dua; Nws tuaj yeem txhim kho cov tshuaj insulin los ntawm kev tswj hwm kev loj hlob hormone secretion, yog li ua kom muaj txiaj ntsig zoo ntawm kev tswj ntshav qabzib.
Kev tswj cov roj metabolism: Kev loj hlob hormone txhawb kev rog rog, nce fatty acid oxidation rau lub zog tsim, thiab txo cov rog. Ipamorelin txhawb kev loj hlob hormone secretion, yog li exerting nws cov kev tswj cov nyhuv ntawm cov roj metabolism. Hauv kev sim tsiaj, tom qab siv Ipamorelin, cov roj cov ntsiab lus hauv cov tsiaj lub cev poob qis, tshwj xeeb tshaj yog nyob rau hauv cov cheeb tsam xws li lub plab. Qhov no yog vim kev loj hlob hormone activates hormone-sensitive lipase (HSL) nyob rau hauv cov roj hlwb, txhawb cov hydrolysis ntawm triglycerides rau fatty acids thiab glycerol. Fatty acids ces nkag mus rau mitochondria rau β-oxidation los tsim lub zog. Kev loj hlob hormone kuj inhibits qhov sib txawv ntawm cov rog rog, txo lawv cov naj npawb thiab ntxiv cov roj hauv lub cev. Ipamorelin, los ntawm kev txhawb nqa kev loj hlob hormone secretion, plays lub luag haujlwm hauv kev tswj cov roj metabolism thiab tswj lub cev hnyav.
Kev cuam tshuam rau cov ntaub so ntswg kho thiab rov tsim dua tshiab
Kev loj hlob hormone plays lub luag haujlwm tseem ceeb hauv cov ntaub so ntswg kho thiab rov tsim dua tshiab. Ipamorelin, los ntawm kev txhawb nqa kev loj hlob hormone secretion, muab cov kev mob zoo rau kev kho cov nqaij mos thiab rov tsim dua tshiab. Hauv cov ntaub so ntswg puas lawm, kev loj hlob hormone tuaj yeem txhawb kev loj hlob ntawm tes thiab kev sib txawv, txhawb kev sib txuas ntawm cov khoom sib txuas ntawm cov khoom siv xws li collagen, thiab ua kom lub qhov txhab zoo. Hauv cov qauv kev raug mob ntawm daim tawv nqaij, tom qab siv Ipamorelin, fibroblast proliferation ntawm qhov txhab nrawm nrawm, collagen deposition nce, thiab lub sijhawm kho qhov txhab yog luv. Qhov no tuaj yeem raug ntaus nqi rau kev loj hlob hormone txhawb fibroblast secretion ntawm cytokines xws li transforming growth factor-β (TGF-β), uas ntxiv nkoos fibroblast proliferation thiab collagen synthesis. Kev loj hlob hormone kuj txhawb kev loj hlob thiab kev tsiv teb tsaws ntawm vascular endothelial hlwb, ua kom yooj yim tsim cov hlab ntsha tshiab los muab cov zaub mov txaus thiab oxygen rau cov ntaub so ntswg puas, yog li ua kom cov ntaub so ntswg sai. Ipamorelin lub luag haujlwm hauv kev txhawb nqa cov ntaub so ntswg kho thiab rov tsim dua tshiab ua rau nws yog ib tus neeg sib tw zoo rau cov ntawv thov hauv kev kho mob, phais yas, thiab lwm yam.
Kev siv Ipamorelin los txhawb kev loj hlob hormone secretion
Muaj peev xwm siv tau hauv kev kho mob
Kev kho mob ntawm kev loj hlob hormone deficiency: Kev loj hlob hormone deficiency yog ib yam mob tshwm sim los ntawm kev loj hlob hormone secretion tsis txaus, yam ntxwv ntawm luv stature thiab ncua kev loj hlob thiab kev loj hlob. Piv nrog rau kev hloov pauv cov tshuaj hormones ib txwm muaj, Ipamorelin txhawb nqa kev loj hlob ntawm cov tshuaj hormones endogenous, zam qee qhov kev mob tshwm sim uas cuam tshuam nrog kev siv lub sijhawm ntev ntawm kev loj hlob hormone exogenous. Cov kev tshawb fawb soj ntsuam tau pom tias hauv qee cov neeg mob uas muaj kev loj hlob hormone tsis txaus, kev siv Ipamorelin ua rau muaj kev loj hlob ntawm cov tshuaj hormones, ua kom qhov siab loj hlob, thiab txhim kho lub neej zoo.
Kev tiv thaiv kev laus: Raws li cov neeg muaj hnub nyoog, kev loj hlob hormone secretion maj mam txo, uas yog ze rau ntau lub hnub nyoog txog kev hloov lub cev. Ipamorelin, uas txhawb kev loj hlob hormone secretion, muaj qee lub luag haujlwm hauv kev tiv thaiv kev laus. Los ntawm kev nce qib ntawm cov tshuaj hormones, Ipamorelin tuaj yeem txhim kho lub cev muaj pes tsawg leeg hauv cov neeg laus, nce cov leeg nqaij, txo cov rog, txhim kho pob txha ceev, thiab txhim kho daim tawv nqaij elasticity. Kev sim tshuaj ntsuam xyuas tau pom tias cov neeg laus uas siv Ipamorelin hauv cov koob tshuaj tsim nyog tau txais kev txhim kho hauv lub cev, lub zog, thiab lub hlwb.
Txhawb kev kho qhov txhab: Ipamorelin txhawb nqa cov ntaub so ntswg kho thiab rov tsim dua tshiab los ntawm kev txhawb kev loj hlob hormone secretion. Hauv kev kho mob, rau cov neeg mob uas muaj qee yam kev raug mob, xws li kub hnyiab lossis pob txha, siv Ipamorelin tuaj yeem ua kom lub qhov txhab zoo thiab txo qhov tshwm sim ntawm cov teeb meem. Hauv cov neeg mob kub hnyiab, Ipamorelin tuaj yeem txhawb nqa epithelialization ntawm lub qhov txhab thiab txo qhov caws pliav; Hauv cov neeg mob pob txha, nws tuaj yeem txhawb kev tsim cov pob txha callus thiab ua kom cov pob txha zoo. Qhov no muab cov kev xaiv kho mob tshiab rau kev tswj kev raug mob, nrog lub peev xwm los txhim kho cov txiaj ntsig kev kho mob.
Cov ntawv thov hauv Cov Tshuaj Kho Mob
Vim nws lub peev xwm los txhawb kev loj hlob hormone secretion, nws tuaj yeem ua rau cov leeg nqaij, txhim kho kev ua kis las, thiab ua kom rov qab ua haujlwm zoo dua. Hauv cov neeg ncaws pob koom nrog kev cob qhia siab, Ipamorelin tuaj yeem pab lawv rov qab lub cev muaj zog sai dua, txo cov leeg nqaij, thiab txo qis kev pheej hmoo ntawm kev raug mob. Hauv cov neeg ncaws pob endurance, Ipamorelin tuaj yeem txhim kho kev tawm dag zog los ntawm kev txhawb cov roj metabolism; hauv cov neeg ncaws pob muaj zog, nws tuaj yeem ua kom cov leeg muaj zog thiab lub zog.
Xaus
Nyob rau hauv cov ntsiab lus, raws li ib tug pentapeptide uas txhawb kev loj hlob hormone secretion, Ipamorelin qhia lub luag hauj lwm tseem ceeb nyob rau hauv kev loj hlob thiab kev loj hlob, kev tswj metabolic, kho cov ntaub so ntswg, thiab ntau yam kev siv cov cheeb tsam.
Qhov chaw
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[2] Adeghate E, Ponery AS, Emirates U.A. ORIGINALARTICLE Mechanism ntawm ipamorelin-evoked insulin tso tawm los ntawm cov txiav txiav ntawm cov nas ib txwm muaj thiab mob ntshav qab zib, 2004 [C]. https://api.semanticscholar.org/CorpusID:74621068
[3] Raun K, Hansen BS, Johansen NL, et al. Ipamorelin, thawj xaiv kev loj hlob hormone secretagogue.[J]. European Journal of Endocrinology, 1998, 139 5: 552-561.
Cov khoom muaj rau kev tshawb fawb siv nkaus xwb:
