Los ntawm Cocer Peptides 
1 month ago
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
Txij li thaum nws nrhiav tau nyob rau hauv 1999, ghrelin tau tshwm sim los ua ib tug focal point ntawm kev tshawb fawb nyob rau hauv lub neej sciences vim nws tshwj xeeb physiological functions thiab broad biological teebmeem. Ghrelin plays lub luag haujlwm tseem ceeb hauv kev tswj hwm kev tso tawm ntawm kev loj hlob hormone (GH) thiab tseem koom nrog ntau yam tseem ceeb ntawm lub cev, nrog rau kev sib npaug ntawm lub zog, kev noj qab haus huv, kev ua haujlwm ntawm plab hnyuv, lub plawv homeostasis, thiab neuroprotection.
Daim duab 1 Ghrelin hormone hauv nws daim ntawv tsis ua haujlwm (desacyl ghrelin) hloov mus rau nws daim ntawv nquag (acyl ghrelin).
Qauv thiab Kev faib tawm ntawm Ghrelin
(1) Qauv
Chemical Composition: Ghrelin yog ib qho polypeptide uas muaj 28 amino acids, nrog rau nws cov qauv tseem ceeb uas muaj kev txuag siab thoob plaws ntau hom. Hauv tib neeg, cov amino acid ib ntus ntawm ghrelin yog GSSFLSPEHQRVQQRKESKKPPAKLQPR. Nws qhov tshwj xeeb tshwj xeeb yog kev hloov kho octanoylation ntawm serine residue ntawm txoj hauj lwm 3, uas yog qhov tseem ceeb rau ghrelin txoj kev khi rau kev loj hlob hormone-tso cov tshuaj hormones receptor (GHS-R) thiab kev tawm dag zog ntawm nws txoj haujlwm lom neeg.
Isomers: Ntxiv rau cov classic octanoylated Ghrelin, kuj tseem muaj deacetylated Ghrelin thiab lwm yam isomers. Txawm hais tias deacetylated Ghrelin tsis muaj kev hloov kho octanoylation thiab tsis muaj peev xwm los khi rau GHS-R nrog kev sib raug zoo siab, kev tshawb fawb tau pom tias nws tuaj yeem ua rau muaj txiaj ntsig lom neeg los ntawm lwm yam tsis paub receptors lossis cov txheej txheem.
(2) Kev faib tawm
Cov ntaub so ntswg faib: Ghrelin feem ntau yog synthesized thiab secreted los ntawm acid-secreting hlwb nyob rau hauv lub gastric fundic glands thiab kuj qhia nyob rau hauv ntau yam ntaub so ntswg thiab kabmob, nrog rau cov hnyuv me, pancreas, hypothalamus, thiab pituitary caj pas. Nyob rau hauv txoj hnyuv, ghrelin qhia qib txo qis ntawm lub plab mus rau cov hnyuv. Nyob rau hauv lub hauv nruab nrab lub paj hlwb, ghrelin yog heev nthuav nyob rau hauv cov cheeb tsam xws li lub arcuate nucleus thiab paraventricular nucleus ntawm lub hypothalamus, uas yog zoo txuam nrog qab los noj mov kev cai, lub zog metabolism, thiab neuroendocrine regulation.
Cellular localization: Nyob rau hauv lub plab, Ghrelin feem ntau qhia nyob rau hauv lub endocrine hlwb ntawm lub plab hnyuv mucosa, uas muaj peev xwm ntes tau cov zaub mov nyob rau hauv lub plab hnyuv ib ntsuj av thiab xa cov teeb liab mus rau lub hauv paus paj hlwb los ntawm Ghrelin secretion. Nyob rau hauv lub caj pas pituitary, Ghrelin tuaj yeem ua ncaj qha rau kev loj hlob hormone hlwb los tswj kev loj hlob hormone tso tawm.
Mechanism of Action of Growth Hormone-Tshuaj Peptide
(1) Kev khi rau cov neeg txais kev pab
GHS-R-mediated signaling pathway: Thawj cov teebmeem lom neeg ntawm Ghrelin tau ua tiav los ntawm kev khi rau kev loj hlob hormone-tso cov tshuaj hormone 1a (GHS-R1a). GHS-R1a yog G protein-coupled receptor dav dav nyob rau hauv pituitary caj pas, hypothalamus, thiab lwm yam ntaub so ntswg peripheral. Raws li kev khi rau GHS-R1a, ghrelin activates G proteins, uas nyob rau hauv lem qhib lub phospholipase C (PLC)-inositol trisphosphate (IP3)-calcium ion (Ca⊃2; ⁺) taw qhia txoj hauv kev, ua rau kom muaj kev nce hauv intracellular Ca⊃2 cov tshuaj hormones, thiab tswj kev loj hlob ntawm lwm yam. muaj nuj nqi.
Non-GHS-R-mediated mechanisms: Ntxiv nrog rau GHS-R1a, cov kev tshawb fawb tau pom tias ghrelin kuj tseem tuaj yeem ua rau muaj kev phom sij los ntawm kev sib cuam tshuam nrog lwm cov receptors lossis cov kua nplaum membrane.
Daim duab 2 Ghrelin exerts nws cov teebmeem nyob rau hauv lub hypothalamus ntawm peb txoj kev sib txawv.
(2) Kev cai ntawm cov noob qhia
Hypothalamic-pituitary axis-hais txog cov noob: Ghrelin tuaj yeem tswj cov kev qhia ntawm ntau cov noob hauv hypothalamic-pituitary axis. Nyob rau theem pituitary, ghrelin tuaj yeem txhim kho qhov kev hloov pauv ntawm cov tshuaj hormones loj hlob, txhawb kev sib txuas thiab tso tawm ntawm kev loj hlob hormone. Hauv hypothalamus, ghrelin tuaj yeem cuam tshuam qhov kev qhia ntawm kev loj hlob hormone-tso tshuaj hormone (GHRH) thiab somatostatin (SS), tsis ncaj qha tswj kev loj hlob hormone tso tawm los ntawm kev hloov pauv ntawm GHRH thiab SS. Tshwj xeeb, ghrelin tuaj yeem txhawb nqa GHRH secretion thaum inhibiting SS secretion, yog li synergistically txhawb kev loj hlob hormone tso tawm.
Lub zog metabolism ntsig txog cov noob: Hauv cov ntaub so ntswg adipose thiab lub siab, ghrelin tswj cov kev qhia ntawm cov noob ntsig txog lub zog metabolism. Piv txwv li, ghrelin tuaj yeem txhim kho qhov kev qhia ntawm peroxisome proliferator-activated receptor γ (PPARγ), txhawb kev sib txawv ntawm adipocytes thiab lipogenesis; Nyob rau tib lub sijhawm, hauv daim siab, ghrelin tswj cov kev qhia ntawm cov noob ntsig txog gluconeogenesis, cuam tshuam rau homeostasis ntawm cov ntshav qabzib.
Physiological teebmeem ntawm kev loj hlob hormone-tso peptide
(1) Txhawb kev loj hlob hormone tso tawm
Kev txiav txim ncaj qha rau ntawm lub caj pas pituitary: Ghrelin yog lub zog loj hlob hormone-tso tawm tus neeg saib xyuas uas ncaj qha ua rau cov tshuaj hormones loj hlob hauv lub caj pas pituitary, txhawb kev sib txuas thiab tso tawm ntawm kev loj hlob hormone los ntawm GHS-R1a-mediated signaling pathway. Piv nrog rau kev loj hlob hormone-tso hormone (GHRH), ghrelin txhawb kev loj hlob hormone tso tawm sai dua, thiab ob qho tib si muaj txiaj ntsig zoo. Nyob rau hauv physiological tej yam kev mob, ghrelin, GHRH, thiab somatostatin koom ua ke tswj lub pulsatile secretion ntawm kev loj hlob hormone, tswj kev loj hlob hormone theem.
Cov teebmeem ntawm kev loj hlob: Kev loj hlob hormone plays lub luag haujlwm tseem ceeb hauv kev txhawb nqa lub cev kev loj hlob thiab kev loj hlob. Ghrelin indirectly influences kev loj hlob los ntawm kev txhawb kev tso tawm ntawm kev loj hlob hormone. Thaum lub sij hawm me nyuam yaus thiab cov hluas, ib txwm tso tawm ntawm Ghrelin yog qhov tseem ceeb rau cov txheej txheem xws li kev loj hlob ntawm pob txha thiab cov leeg nqaij. Hauv cov neeg mob uas muaj kev loj hlob hormone tsis txaus, ghrelin secretion feem ntau qis. Exogenous kev tswj hwm ntawm ghrelin lossis nws cov analogues tuaj yeem ua rau muaj kev loj hlob ntawm cov tshuaj hormones thiab txhawb kev loj hlob thiab kev loj hlob.
(2) Kev Tswj Xyuas Lub Zog Metabolism
Txoj Cai Kev Noj Qab Haus Huv: Ghrelin, lub npe hu ua 'kev tshaib kev nqhis,' yog ib qho tseem ceeb taw qhia molecule tswj qab los noj mov. Hauv arcuate nucleus ntawm hypothalamus, ghrelin khi rau GHS-R1a receptors ntawm neuropeptide Y (NPY) / agouti-related protein (AgRP) neurons, txhawb kev tso tawm NPY thiab AgRP, yog li ua kom qab los noj mov thiab txhawb kev noj zaub mov. Ghrelin tseem cuam tshuam kev noj qab haus huv los ntawm kev tswj hwm cov haujlwm ntawm corticotropin-tso hormone (CRH) neurons hauv paraventricular nucleus ntawm hypothalamus. Thaum yoo mov, qib ghrelin nce, ua rau muaj kev tshaib plab; Tom qab noj mov, qib ghrelin sai zuj zus, txhim kho qhov kev xav ntawm fullness.
Kev tswj hwm lub zog: Ghrelin kuj koom nrog kev tswj hwm ntawm lub zog metabolism, tswj lub cev lub zog sib npaug. Ghrelin txhawb nqa lipolysis, nce fatty acid oxidation, thiab txhim kho lub cev lub zog. Ghrelin inhibits insulin secretion, txo cov ntaub so ntswg peripheral uptake thiab siv cov piam thaj, thiab ua kom cov ntshav qabzib nce siab, muab lub cev muaj zog ntxiv. Kev hais tawm siab ntev ntawm ghrelin tuaj yeem ua rau muaj kev noj ntau dhau, rog rog, thiab tom qab cov kab mob metabolic xws li rog rog.
(3) cuam tshuam rau kev ua haujlwm ntawm plab hnyuv
Gastric acid secretion thiab gastrointestinal motility: Nyob rau hauv lub plab zom mov, ghrelin plays lub luag hauj lwm tseem ceeb nyob rau hauv lub plab acid secretion thiab gastrointestinal motility. Ghrelin nkoos plab mucosal parietal hlwb kom secrete gastric acid, tswj cov acidic ib puag ncig nyob rau hauv lub plab, uas pab nyob rau hauv cov zaub mov digestion thiab nqus. Ghrelin txhawb lub plab zom mov peristalsis, txhim kho kev txav mus los hauv plab hnyuv thiab ua kom cov zaub mov tawm ntawm lub plab zom mov. Hauv qee yam kab mob hauv plab, xws li kev ua haujlwm dyspepsia thiab gastroparesis, qhov txawv txav ntawm Ghrelin tuaj yeem ua rau muaj kev cuam tshuam hauv plab acid secretion thiab gastrointestinal motility.
Kev tiv thaiv ntawm plab hnyuv mucosa: Ghrelin muaj kev tiv thaiv ntawm lub plab hnyuv mucosa. Nws txhawb kev loj hlob thiab kho cov kab mob hauv plab hnyuv mucosal, txhim kho mucosal barrier muaj nuj nqi, thiab tiv thaiv kev puas tsuaj los ntawm cov khoom tsis zoo xws li gastric acid thiab Helicobacter pylori. Hauv cov qauv kab mob xws li mob plab thiab duodenal ulcers, exogenous kev tswj hwm ntawm ghrelin accelerates kho rwj thiab txo qhov kev puas tsuaj ntawm mucosal.
(4) Kev tswj hwm ntawm cov hlab plawv
Kev tswj hwm lub plawv: Ghrelin tau nthuav dav hauv plawv thiab ua lub luag haujlwm tseem ceeb hauv kev ua haujlwm plawv. Ghrelin txhim kho myocardial contractility, ua rau kom lub plawv tso zis, thiab txhim kho lub plawv dhia ua haujlwm. Nyob rau hauv myocardial ischemia-reperfusion raug mob qauv, ghrelin txo myocardial cell apoptosis thiab necrosis, txo infarct loj, thiab exerts ib tug cardioprotective nyhuv. Nws cov txheej txheem tuaj yeem cuam tshuam nrog kev ua kom lub cev muaj sia nyob hauv lub cev, xws li phosphoinositide 3-kinase (PI3K) / protein kinase B (Akt) qhia txoj hauv kev.
Vascular Tension Regulation: Ghrelin tswj vascular nro thiab tswj cov ntshav siab. Nws ua rau vascular du leeg hlwb txhawm rau inhibit qhov cuam tshuam ntawm vasoconstrictive tshuaj xws li angiotensin II, ua rau vasodilation, txo qis peripheral vascular tsis kam, thiab yog li txo cov ntshav siab. Ghrelin kuj inhibits qhov kev qhia ntawm vascular endothelial cell adhesion molecules, txo cov adhesion thiab infiltration ntawm inflammatory cells, exerting ib vascular tiv thaiv, thiab tiv thaiv kev loj hlob ntawm atherosclerosis.
(5) Cov teebmeem neuroprotective
Neuronal ciaj sia taus thiab kev loj hlob: Hauv lub paj hlwb, ghrelin muaj kev tiv thaiv zoo rau cov neurons. Nws txhawb txoj kev loj hlob thiab kev sib txawv ntawm cov kab mob neural qia hlwb, nce tus naj npawb ntawm cov neurons, thiab tswj cov kev loj hlob thiab kev ua haujlwm ntawm lub paj hlwb. Hauv cov qauv ntawm cov kab mob neurodegenerative xws li Alzheimer's kab mob thiab Parkinson tus kab mob, ghrelin tuaj yeem inhibit neuronal apoptosis, txo cov lus teb neuroinflammatory, thiab txhim kho kev txawj ntse thiab lub cev muaj zog. Nws cov txheej txheem tiv thaiv neuroprotective tuaj yeem cuam tshuam txog kev tswj hwm cov lus teb hauv lub cev oxidative kev ntxhov siab, inhibiting apoptosis signaling pathways, thiab txhawb kev tso tawm ntawm cov neurotransmitters.
Neuroendocrine Regulation: Raws li kev tswj hwm neuroendocrine, Ghrelin koom nrog tswj kev ua haujlwm ntawm hypothalamic-pituitary-adrenal axis (HPA axis). Nyob rau hauv cov xwm txheej kev ntxhov siab, qib siab ghrelin inhibit qhov ua kom ntau dhau ntawm HPA axis, txo qis corticosteroid secretion thiab yog li txo qis kev ntxhov siab vim kev puas tsuaj rau lub cev. Tsis tas li ntawd, ghrelin tswj cov hypothalamic-pituitary-thyroid axis (HPT axis) thiab hypothalamic-pituitary-gonadal axis (HPG axis), tswj lub homeostasis ntawm lub neuroendocrine system.
(6) Lwm yam physiological cuam tshuam
Kev tswj kev tiv thaiv kab mob: Ghrelin kuj ua lub luag haujlwm hauv kev tiv thaiv kab mob. Nws tuaj yeem tswj hwm kev ua haujlwm ntawm lub cev tiv thaiv kab mob, txhawb kev loj hlob thiab kev sib txawv ntawm lymphocytes, thiab txhim kho lub cev tiv thaiv kab mob. Hauv cov xeev inflammatory, ghrelin tuaj yeem tiv thaiv kev tso tawm ntawm cov kab mob cytokines, xws li qog necrosis factor-α (TNF-α) thiab interleukin-6 (IL-6), yog li txo cov inflammatory teb thiab exerting immunomodulatory thiab anti-inflammatory teebmeem.
Kev cai ntawm pob txha Metabolism: Ghrelin muaj cov kev tswj xyuas ntawm cov pob txha metabolism. Nws txhawb kev loj hlob thiab kev sib txawv ntawm osteoblasts, inhibits kev ua haujlwm ntawm osteoclasts, yog li ua kom cov pob txha loj thiab txhawb kev tsim cov pob txha. Hauv cov neeg mob osteoporosis, qib ghrelin feem ntau txo qis, qhia tias ghrelin tuaj yeem cuam tshuam nrog kev txhim kho pob txha. Exogenous kev tswj hwm ntawm ghrelin los yog nws cov analogues yuav muab cov tswv yim kho tshiab rau cov pob txha.
Kev siv ntawm Kev Loj Hlob Hormone-Tshuaj Peptide
(1) Kev siv tshuaj kho mob
Kev Loj Hlob Hormone Deficiency: Rau cov neeg mob uas tsis muaj kev loj hlob hormone, Ghrelin thiab nws cov analogues tuaj yeem ua cov tshuaj kho mob. Los ntawm kev txhawb kev tso tawm ntawm kev loj hlob hormone, lawv txhawb kev loj hlob thiab kev loj hlob ntawm cov neeg mob. Piv nrog rau cov tshuaj hloov pauv cov tshuaj loj hlob ib txwm muaj, Ghrelin thiab nws cov tshuaj analogues muaj kev nyab xeeb zoo dua thiab ua kom ntev, thiab tuaj yeem txhawb kev loj hlob ntawm ntau lub cev tsim nyog los ntawm kev tswj xyuas qhov tso tawm ntawm cov tshuaj endogenous loj hlob.
Daim duab 3 Endocrine regulation ntawm GH thiab kho blockade.
Cov Kab Mob Metabolic
Kev rog thiab ntshav qab zib: Hauv kev kho mob rog, txawm hais tias Ghrelin raug xa mus rau 'kev tshaib kev nqhis,' tswj cov qib Ghrelin lossis nws cov kev taw qhia yuav txhim kho lub zog metabolism, txo qis qab los noj mov, thiab ua kom poob phaus. Txhim kho Ghrelin receptor antagonists los thaiv Ghrelin khi rau receptors tuaj yeem txo qis qab los noj mov thiab txo cov khoom noj. Rau cov neeg mob ntshav qab zib mellitus, Ghrelin tuaj yeem ua rau muaj txiaj ntsig zoo ntawm cov ntshav qabzib los ntawm cov txheej txheem xws li tswj hwm cov tshuaj insulin secretion thiab txhim kho insulin tsis kam. Exogenous kev tswj hwm ntawm Ghrelin txhim kho cov ntshav tswj ntshav qabzib thiab insulin rhiab heev hauv cov nas ntshav qab zib, muab kev nkag siab tshiab rau kev kho mob ntshav qab zib.
Metabolic Syndrome: Metabolic Syndrome yog ib pab pawg ntawm cov kab mob uas muaj kev rog rog, kub siab, hyperglycemia, thiab dyslipidemia. Vim nws lub luag haujlwm hauv lub zog metabolism thiab tswj cov hlab plawv, ghrelin tuaj yeem dhau los ua lub hom phiaj rau kev kho mob metabolic syndrome. Los ntawm kev tswj hwm qib ghrelin, nws tuaj yeem ua rau tib lub sijhawm txhim kho ntau yam kab mob metabolic hauv cov neeg mob uas muaj cov kab mob metabolic, xws li poob phaus, txo ntshav siab, thiab txhim kho cov ntshav qabzib thiab lipids txawv txav.
Kab mob plab:
Functional dyspepsia thiab gastroparesis: Rau cov neeg mob uas muaj kev ua haujlwm dyspepsia thiab gastroparesis, ghrelin thiab nws cov analogues tuaj yeem txhim kho cov tsos mob plab thiab ua kom lub plab zom mov los ntawm kev txhawb nqa plab hnyuv thiab nce gastric acid secretion. Kev siv ghrelin analogues tuaj yeem txo cov tsos mob xws li mob plab thiab tsam plab hauv cov neeg mob uas muaj kev ua haujlwm dyspepsia, yog li txhim kho lawv lub neej zoo.
Gastrointestinal ulcers: Vim Ghrelin cov kev tiv thaiv ntawm plab hnyuv mucosa, nws muaj peev xwm txhawb ulcer kho thiab yog li muaj peev xwm siv tau tus nqi hauv kev kho mob plab ulcers. Exogenous kev tswj hwm ntawm Ghrelin los yog nws cov analogues yuav ua rau kom cov txheej txheem kho rwj thiab txo qhov mob rov qab.
Cov kab mob plawv:
Myocardial ischemia-reperfusion raug mob: Hauv kev kho mob ntawm myocardial ischemia-reperfusion raug mob, Ghrelin, vim nws cov teebmeem cardioprotective, tuav cov lus cog tseg raws li cov tshuaj kho tshiab. Los ntawm kev tswj hwm Ghrelin los yog nws cov analogues ua ntej lossis thaum lub sij hawm myocardial ischemia-reperfusion, nws tuaj yeem txo qhov kev puas tsuaj ntawm myocardial cell, txo qhov loj me me, thiab txhim kho kev ua haujlwm ntawm lub plawv. Kev sim tsiaj txhu thiab kev sim tshuaj ntsuam xyuas tau pom cov txiaj ntsig tau zoo, muab cov tswv yim tshiab rau kev kho mob myocardial ischemia-reperfusion raug mob.
Lub plawv tsis ua hauj lwm: Hauv cov neeg mob uas muaj lub plawv tsis ua hauj lwm, Ghrelin feem ntau txo qis thiab cuam tshuam nrog kev mob plawv tsis ua hauj lwm. Ntxiv nrog Ghrelin lossis nws cov analogues tuaj yeem txhim kho kev ua haujlwm hauv plawv hauv cov neeg mob plawv tsis ua haujlwm los ntawm kev txhim kho myocardial contractility, txhim kho plawv lub zog metabolism, thiab inhibiting myocardial cell apoptosis, yog li txhim kho cov neeg mob lub neej zoo thiab kev ciaj sia.
Cov Kab Mob Neurodegenerative:
Alzheimer's Disease thiab Parkinson's Disease: Muab Ghrelin's neuroprotective teebmeem, nws tuav cov nqi siv nyiaj hauv kev kho cov kab mob neurodegenerative xws li Alzheimer's disease thiab Parkinson's disease. Los ntawm kev tswj hwm Ghrelin lossis nws cov analogues, nws tuaj yeem cuam tshuam neuronal apoptosis, txo cov lus teb neuroinflammatory, thiab txhim kho cov neeg mob kev txawj ntse thiab lub cev muaj zog.
Stroke thiab Traumatic Brain Injury: Nyob rau hauv mob neurological raug mob xws li mob stroke thiab traumatic lub hlwb raug mob, Ghrelin yuav exert neuroprotective los ntawm mechanisms xws li txo neuronal puas thiab txhawb neural regeneration. Cov kev tshawb fawb tau pom tias nyob rau hauv cov qauv tsiaj ntawm mob stroke lossis mob hlwb raug mob, kev siv Ghrelin tuaj yeem txo qhov loj me me lossis txo qhov kev puas hlwb ntawm lub hlwb, yog li txhim kho cov txiaj ntsig ntawm cov paj hlwb. Ghrelin tuaj yeem ua ib qho kev kho mob ntxiv rau kev mob stroke thiab kev puas tsuaj rau lub hlwb, ntxiv dag zog rau cov neeg mob cov txiaj ntsig rov qab los.
Cov lus xaus
Raws li kev ua haujlwm ntau yam endogenous peptide, Ghrelin plays lub luag haujlwm tseem ceeb hauv ntau yam txheej txheem physiological, suav nrog kev loj hlob thiab kev loj hlob, lub zog metabolism, kev ua haujlwm ntawm plab hnyuv, lub plawv system homeostasis, thiab neuroprotection.
Qhov chaw
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