By Cocer Peptides 
1 ọnwa gara aga
Akụkọ niile na ozi ngwaahịa enyere na webụsaịtị a bụ naanị maka mgbasa ozi na ebumnuche mmụta.
Ngwaahịa ndị enyere na webụsaịtị a bụ naanị maka nyocha in vitro. A na-eme nyocha in vitro (Latin: * na iko *, nke pụtara na ihe eji enyo) na mpụga ahụ mmadụ. Ngwaahịa ndị a abụghị ọgwụ, ndị US Food and Drug Administration (FDA) akwadoghị ya, ha agaghịkwa eji ya gbochie, gwọọ, ma ọ bụ gwọọ ọnọdụ ahụike ọ bụla, ọrịa, ma ọ bụ ọrịa. Iwu amachibidoro nke ọma iwebata ngwaahịa ndị a n'ime ahụ mmadụ ma ọ bụ anụmanụ n'ụdị ọ bụla.
Nchịkọta
Ebe ọ bụ na achọpụtara ya na 1999, ghrelin apụtala dị ka ebe nyocha na sayensị ndụ n'ihi ọrụ physiological pụrụ iche ya na nnukwu mmetụta ndu. Ghrelin na-arụ ọrụ dị oke mkpa n'ịhazi ntọhapụ nke homonụ na-eto eto (GH) ma na-etinyekwa aka na ọtụtụ usoro mmụta anụ ahụ dị mkpa, gụnyere nguzozi ike, nhazi agụụ, ọrụ eriri afọ, homeostasis nke obi, na neuroprotection.
Ọgụgụ 1 Ghrelin hormone n'ụdị adịghị arụ ọrụ (desacyl ghrelin) ka agbanwere n'ụdị ọrụ ya (acyl ghrelin).
Ọdịdị na nkesa nke Ghrelin
(1) Nhazi
Ihe mejupụtara kemịkalụ: Ghrelin bụ polypeptide nke amino acid 28 nwere, yana usoro ya bụ isi na-egosipụta nchekwa dị elu n'ofe ụdị dị iche iche. N'ime mmadụ, usoro amino acid nke ghrelin bụ GSSFLSPEHQRVQQRKESKKPPAKLQPR. Akụkụ pụrụ iche ya bụ mgbanwe octanoylation na ihe fọdụrụ na serine na ọnọdụ 3, nke dị oke mkpa maka njikọ ghrelin na onye na-anabata homonụ na-ewepụta homonụ na-eto eto (GHS-R) yana ịgba mbọ na-arụ ọrụ ndu ya.
Isomers: Na mgbakwunye na Ghrelin octanoylated kpochapụwo, enwekwara Ghrelin deacetylated na isomers ndị ọzọ. Ọ bụ ezie na deacetylated Ghrelin enweghị mgbanwe octanoylation na enweghị ikike ijikọ GHS-R na mmekọrịta dị elu, nyocha egosila na ọ nwere ike ịkpata mmetụta dị ndụ site na ndị nnabata ma ọ bụ usoro ndị ọzọ amabeghị.
(2) Nkesa
Nkesa anụ ahụ: Ghrelin bụ nke a na-emepụta ma na-ezobe ya site na mkpụrụ ndụ na-ezobe acid na gastric fundic glands ma na-egosipụtakwa n'ọtụtụ anụ ahụ na akụkụ ahụ, gụnyere eriri afọ, pancreas, hypothalamus, na pituitary gland. N'ime eriri afọ eriri afọ, ọkwa okwu ghrelin na-ebelata nke nta nke nta site na afọ ruo obere eriri afọ. Na usoro nhụjuanya nke etiti, a na-egosipụta ghrelin nke ukwuu na mpaghara ndị dị ka arcuate nucleus na paraventricular nucleus nke hypothalamus, bụ ndị na-ejikọta ya na nchịkwa agụụ, metabolism ume, na nchịkwa neuroendocrine.
Mpaghara cellular: N'ime afọ, a na-egosipụta Ghrelin n'ụzọ bụ isi na sel endocrine nke mucosa gastric, nke nwere ike ịchọpụta ọnọdụ oriri na-edozi ahụ n'ime eriri afọ ma na-ebufe akara na usoro nhụjuanya nke etiti site na nzuzo Ghrelin. Na pituitary gland, Ghrelin nwere ike na-arụ ọrụ ozugbo na mkpụrụ ndụ homonụ na-eto eto iji mezie mwepụta homonụ uto.
Usoro nke Omume nke Hormone na-ewepụta Peptide
(1) Ijide n'aka ndị nnabata
Ụzọ nrịbama nke GHS-R: A na-enweta mmetụta ndị bụ isi nke ndụ Ghrelin site na ijikọ na hormone na-ewepụta hormone receptor 1a (GHS-R1a). GHS-R1a bụ ihe nnabata protein jikọtara ọnụ nke G na-ekesa na pituitary gland, hypothalamus na anụ ahụ ndị ọzọ. Mgbe ejikọtara ya na GHS-R1a, ghrelin na-arụ ọrụ protein G, nke n'aka nke ya na-eme ka phospholipase C (PLC) -inositol trisphosphate (IP3) -calcium ion (Ca⊃2; ⁺) ụzọ na-egosi ụzọ, na-eduga n'ịbawanye na intracellular Ca⊃2; ⁺ itinye uche na ntọhapụ na-eme ka mmepụta hormone na-eme ka ahụ dịkwuo elu.
Usoro mgbasa ozi na-abụghị GHS-R: Na mgbakwunye na GHS-R1a, ọmụmụ egosila na ghrelin nwekwara ike ịkpata mmetụta dị ndụ site na mmekọrịta ya na ndị nnabata ndị ọzọ ma ọ bụ protein membrane.
Ọgụgụ 2 Ghrelin na-arụ ọrụ ya na hypothalamus site na ụzọ atọ dị iche iche.
(2) Iwu nke okwu mkpụrụ ndụ ihe nketa
Mkpụrụ ndụ ihe nketa metụtara hypothalamic-pituitary: Ghrelin nwere ike ịhazi okwu nke ọtụtụ mkpụrụ ndụ ihe nketa na axis hypothalamic-pituitary. N'ọkwa pituitary, ghrelin nwere ike mezigharị ederede nke mkpụrụ ndụ homonụ uto, na-akwalite njikọ na mwepụta nke homonụ uto. Na hypothalamus, ghrelin nwere ike imetụta ngosipụta nke homonụ na-ewepụta homonụ na-eto eto (GHRH) na somatostatin (SS), na-achịkwa ntọhapụ nke homonụ na-eto eto na-apụtaghị ìhè site n'ịgbanwe ihe nzuzo nke GHRH na SS. Kpọmkwem, ghrelin nwere ike kpalite nzuzo nke GHRH ka ọ na-egbochi nzuzo SS, si otú ahụ na-akwalite mwepụta homonụ uto.
Mkpụrụ ndụ ihe nketa metụtara ike metabolism: N'ime anụ ahụ adipose na imeju, ghrelin na-achịkwa okwu mkpụrụ ndụ ihe nketa metụtara metabolism ike. Dịka ọmụmaatụ, ghrelin nwere ike imeziwanye okwu nke peroxisome proliferator-activated γ (PPARγ), na-akwalite ọdịiche adipocyte na lipogenesis; N'otu oge, na imeju, ghrelin na-achịkwa okwu mkpụrụ ndụ ihe nketa metụtara gluconeogenesis, na-emetụta homeostasis nke ọkwa glucose ọbara.
Mmetụta anụ ahụ nke peptide na-ewepụta homonụ uto
(1) Na-akwalite mwepụta homonụ nke uto
Omume kpọmkwem na gland pituitary: Ghrelin bụ onye na-ewepụta hormone na-eto eto nke na-arụ ọrụ ozugbo na mkpụrụ ndụ hormone na-eto eto na gland pituitary, na-akwalite njikọ na ntọhapụ nke hormone na-eto eto site na ụzọ mgbaàmà GHS-R1a. E jiri ya tụnyere hormone na-ewepụta homonụ na-eto eto (GHRH), ghrelin na-akpali ntọhapụ nke hormone uto ngwa ngwa, ha abụọ nwere mmetụta synergistic. N'okpuru ọnọdụ physiological, ghrelin, GHRH, na somatostatin na-ejikọta ọnụ na-achịkwa mmepụta nke homonụ uto, na-ejigide ọkwa hormone uto nkịtị.
Mmetụta na uto: hormone na-eto eto na-ekere òkè dị mkpa n'ịkwalite uto na mmepe nke anụ ahụ. Ghrelin na-emetụta uto na-apụtaghị ìhè site n'ịkwalite ntọhapụ nke hormone ibu. N'oge nwata na n'oge uto, nzuzo nkịtị nke Ghrelin dị oke mkpa maka usoro dịka uto skeletal na mmepe akwara. N'ime ndị ọrịa nwere ụkọ homonụ na-eto eto, ọkwa nzuzo ghrelin na-adịkarị ala. Nlekọta nke ghrelin ma ọ bụ analogues ya nwere ike ịbawanye ọkwa hormone uto nke ọma ma kwalite uto na mmepe.
(2) Iwu nke Metabolism Energy
Iwu agụụ: Ghrelin, nke a maara dị ka 'hormone agụụ,' bụ ihe dị mkpa na-egosi molekul na-achịkwa agụụ. Na arcuate nucleus nke hypothalamus, ghrelin na-ejikọta GHS-R1a ndị na-anabata ya na neuropeptide Y (NPY) / protein metụtara neuropeptide (AgRP), na-akpali ntọhapụ nke NPY na AgRP, si otú ahụ na-amụba agụụ na ịkwalite oriri nri. Ghrelin na-emetụtakwa agụụ n'ụzọ na-edoghị anya site n'ịhazi ọrụ nke corticotropin na-ahapụ hormone (CRH) neurons na paraventricular nucleus nke hypothalamus. N'oge ibu ọnụ, ọkwa ghrelin na-ebili, na-ebute agụụ; mgbe ị risịrị nri, ọkwa ghrelin na-ebelata ngwa ngwa, na-eme ka mmetụta nke afọ ju.
Usoro nguzozi ike: Ghrelin na-ekerekwa òkè na nhazi nke metabolism ike, na-ejigide nguzozi ike nke ahụ. Ghrelin na-akwalite lipolysis, na-abawanye oxidation fatty acid, ma na-eme ka ahụ ike nweta ume. Ghrelin na-egbochi mmepụta insulin, na-ebelata nnabata anụ ahụ dị n'akụkụ na ojiji nke glucose, ma na-ebuli ọkwa glucose ọbara, na-enye ahụ ahụ ike ọzọ. Ngosipụta dị elu nke ghrelin na-adịte aka nwere ike iduga oke ike oriri, mkpokọta abụba, yana nsogbu metabolic dị ka oke ibu.
(3) Mmetụta na ọrụ eriri afọ
Ihe nzuzo nke acid gastric na motility eriri afọ: N'ime tract gastrointestinal, ghrelin na-arụ ọrụ nhazi dị mkpa na nzuzo acid gastric na motility eriri afọ. Ghrelin na-akpali sel mucosal mucosal parietal nke eriri afọ iji zoo acid gastric, na-achịkwa gburugburu acidic n'ime afọ, nke na-enyere aka mgbari nri na nnabata. Ghrelin na-akwalite peristalsis nke eriri afọ, na-eme ka mmegharị ahụ na-akpali akpali na tract gastrointestinal na-eme ka mwepụ nke nri si na eriri afọ. N'ụfọdụ nsogbu eriri afọ, dị ka dyspepsia na-arụ ọrụ na gastroparesis, ọkwa Ghrelin na-adịghị mma nwere ike ibute mmebi na secretion acid gastric na motility eriri afọ.
Nchedo nke Mucosa Gastrointestinal: Ghrelin nwere mmetụta nchebe na mucosa eriri afọ. Ọ na-akwalite mmụba na mmezi nke mkpụrụ ndụ mucosal eriri afọ, na-eme ka ọrụ mgbochi mucosal dịkwuo mma, na-echebekwa mmebi nke ihe ndị na-emerụ ahụ dị ka gastric acid na Helicobacter pylori kpatara. N'ụdị ọrịa dịka ọnya afọ na ọnya duodenal, nchịkwa exogenous nke ghrelin na-eme ka ọgwụgwọ ọnya dị ngwa ma na-ebelata oke mmebi nke mucosal.
(4) Nhazi usoro obi obi
Usoro ọrụ obi obi: A na-egosipụta Ghrelin n'ọtụtụ ebe n'ime obi ma na-arụ ọrụ nchịkwa dị mkpa na ọrụ obi. Ghrelin na-akwalite myocardial contractility, na-abawanye mmepụta obi, ma na-eme ka ọrụ mgbapụta obi dịkwuo mma. N'ụdị mmerụ ahụ nke myocardial ischemia-reperfusion, ghrelin na-ebelata apoptosis cell myocardial apoptosis na necrosis, na-ebelata nha infarct, ma na-arụkwa mmetụta cardioprotective. Usoro ya nwere ike jikọta ya na ịgbalite ụzọ akara intracellular intracellular, dị ka ụzọ akara ngosi phosphoinotide 3-kinase (PI3K)/protein kinase B (Akt).
Usoro nchịkwa akwara vaskụla: Ghrelin na-achịkwa esemokwu vaskụla ma na-edobe ọbara mgbali elu. Ọ na-arụ ọrụ na mkpụrụ ndụ anụ ahụ dị nro nke vaskụla iji gbochie mmetụta nke vasoconstrictive bekee dị ka angiotensin II, na-akpata vasodilation, na-ebelata nguzogide vaskụla, ma si otú a na-ebelata ọbara mgbali. Ghrelin na-egbochikwa okwu nke vaskụla endothelial cell adhesion molecules, na-ebelata adhesion na ntinye nke mkpụrụ ndụ mkpali, na-emepụta mmetụta nchebe vaskụla, na igbochi mmepe nke atherosclerosis.
(5) Mmetụta neuroprotective
Ịlanarị Neuronal na mmụba: Na usoro ụjọ ahụ, ghrelin nwere mmetụta nchebe na neurons. Ọ na-akwalite mmụba na ọdịiche nke mkpụrụ ndụ sel akwara, na-eme ka ọnụ ọgụgụ nke neurons dịkwuo elu, ma na-eme ka mmepe nkịtị na ọrụ nke usoro ụjọ ahụ. N'ụdị nke ọrịa neurodegenerative dị ka ọrịa Alzheimer na ọrịa Parkinson, ghrelin nwere ike igbochi apoptosis neuronal, belata nzaghachi neuroinflammatory, ma melite ọrụ ọgụgụ isi na moto. Usoro neuroprotective ya nwere ike jikọta ya na ịhazi nzaghachi nrụgide oxidative intracellular, na-egbochi ụzọ akara apoptosis, na ịkwalite ntọhapụ nke neurotransmitters.
Iwu Neuroendocrine: Dị ka ihe na-achịkwa neuroendocrine, Ghrelin na-ekere òkè n'ịhazi ọrụ nke hypothalamic-pituitary-adrenal axis (HPA axis). N'okpuru ọnọdụ nrụgide, ọkwa ghrelin dị elu na-egbochi oke ịgbalite axis HPA, na-ebelata ihe nzuzo corticosteroid ma si otú a na-ebelata mmebi ahụ na-akpata nchekasị. Na mgbakwunye, ghrelin na-achịkwa hypothalamic-pituitary-thyroid axis (HPT axis) na hypothalamic-pituitary-gonadadal axis (HPG axis), na-ejigide homeostasis nke sistemụ neuroendocrine.
(6) Mmetụta physiological ndị ọzọ
Usoro mgbochi ọrịa: Ghrelin na-ekerekwa òkè na usoro ahụ ji alụso ọrịa ọgụ. Ọ nwere ike ịhazi ọrụ nke mkpụrụ ndụ na-alụso ọrịa ọgụ, kwalite mmụba na ọdịiche nke lymphocytes, ma kwalite ikike nzaghachi nke ahụ. Na steeti ndị na-egbuke egbuke, ghrelin nwere ike igbochi ntọhapụ nke cytokines na-egbuke egbuke, dị ka tumor necrosis factor-α (TNF-α) na interleukin-6 (IL-6), si otú ahụ na-ebelata nzaghachi mkpali ma na-eme immunomodulatory na mgbochi mkpali mmetụta.
Iwu Metabolism Ọkpụkpụ: Ghrelin nwere mmetụta nchịkwa na metabolism ọkpụkpụ. Ọ na-akwalite mmụba na ọdịiche nke osteoblasts, na-egbochi ọrụ nke osteoclasts, si otú ahụ na-amụba ọkpụkpụ ọkpụkpụ na ịkwalite ọkpụkpụ ọkpụkpụ. N'ime ndị ọrịa nwere osteoporosis, ọkwa ghrelin na-ebelatakarị, na-atụ aro na ghrelin nwere ike jikọta ya na mmepe osteoporosis. Nlekọta nke ghrelin ma ọ bụ analogues ya nwere ike inye usoro ọgwụgwọ ọhụrụ maka osteoporosis.
Ngwa nke peptide na-ewepụta Hormone Uto
(1) Ngwa ọgwụgwọ Clinical
Mmụba Hormone Uto: Maka ndị ọrịa nwere ụkọ homonụ na-eto eto, Ghrelin na analogues ya nwere ike bụrụ ndị nnọchi anya ọgwụgwọ. Site n'ịkwalite ntọhapụ nke hormone na-eto eto, ha na-akwalite uto na mmepe na ndị ọrịa. Tụnyere usoro ọgwụgwọ nnọchi homonụ uto ọdịnala, Ghrelin na analogues ya na-enye nchekwa na nnabata ka mma, ma nwee ike ịkwalite uto n'ụzọ dabara adaba n'ụzọ anụ ahụ site na ịhazi nzuzo nke homonụ uto endogenous.
Ọgụgụ 3 Usoro Endocrine nke GH na mgbochi ọgwụgwọ.
Ọrịa Metabolic
Oke ibu na ọrịa shuga: Na ọgwụgwọ oke ibu, ọ bụ ezie na a na-akpọ Ghrelin dị ka 'hormone agụụ na-agụ,' ịchịkwa ọkwa Ghrelin ma ọ bụ ụzọ mgbaàmà ya nwere ike imeziwanye metabolism ume, belata agụụ, ma nweta ibu ibu. Ịzụlite ndị na-anabata Ghrelin iji gbochie njikọ Ghrelin na ndị na-anabata ya nwere ike igbochi agụụ ma belata oriri. Maka ndị ọrịa nwere ọrịa shuga, Ghrelin nwere ike inwe mmetụta bara uru na ọkwa glucose ọbara site na usoro dị ka ịhazi insulin secretion na ịkwalite nguzogide insulin. Nlekọta nke Ghrelin dịpụrụ adịpụ na-eme ka njikwa glucose ọbara dịkwuo mma yana mmetụta insulin na oke ndị na-arịa ọrịa shuga, na-enye nghọta ọhụrụ maka ọgwụgwọ ọrịa shuga.
Ọrịa Metabolic: Ọrịa Metabolic bụ otu ọrịa nke oke ibu, ọbara mgbali elu, hyperglycemia, na dyslipidemia mara. N'ihi ọrụ ya na metabolism ike na nhazi nke obi, ghrelin nwere ike bụrụ ebumnuche enwere ike ịgwọ ọrịa metabolic syndrome. Site n'ịhazi ọkwa ghrelin, ọ ga-ekwe omume n'otu oge iji kwalite ọtụtụ ihe mgbaàmà nke ọrịa metabolic na ndị ọrịa nwere ọrịa metabolic, dị ka mbelata ibu, mbelata ọbara mgbali, na mmụba nke glucose ọbara na mmebi lipid.
Ọrịa Gastrointestinal:
Dyspepsia na-arụ ọrụ na gastroparesis: Maka ndị ọrịa nwere dyspepsia na-arụ ọrụ na gastroparesis, ghrelin na analogues ya nwere ike imezi mgbaama mgbaze ma mee ka mkpofu gastric dịkwuo elu site na ịkwalite motility eriri afọ na ịba ụba secretion acid gastric. Ojiji nke ghrelin analogues nwere ike belata mgbaàmà dị ka mgbu afọ na elu na afọ ọsịsa na ndị ọrịa nwere dyspepsia na-arụ ọrụ, si otú a na-emeziwanye ndụ ha.
Ọnya afọ: N'ihi mmetụta nchebe Ghrelin na mucosa eriri afọ, ọ nwere ike ịkwalite ọgwụgwọ ọnya ma si otú ahụ nwee uru ngwa ngwa na ọgwụgwọ ọnya afọ. Ịchịkọta Ghrelin ma ọ bụ ihe analogues ya nwere ike ime ka usoro nrụzi ọnyá ahụ dịkwuo ngwa ma belata nlọghachi ọnya.
Ọrịa obi:
Myocardial ischemia-reperfusion mmerụ: Na ọgwụgwọ nke myocardial ischemia-reperfusion mmerụ, Ghrelin, n'ihi na ya cardioprotective mmetụta, na-ekwe nkwa dị ka a akwụkwọ akụkọ na-ahụ maka ọgwụgwọ. Site n'inye Ghrelin ma ọ bụ analogues ya tupu ma ọ bụ n'oge myocardial ischemia-reperfusion, ọ nwere ike ibelata mmebi mkpụrụ ndụ myocardial, belata nha infarct, ma melite ọrụ obi. Nnwale anụmanụ na nsonaazụ nyocha ụlọ ọgwụ egosila nsonaazụ na-ekwe nkwa, na-enye usoro ọhụụ maka ọgwụgwọ nke myocardial ischemia-reperfusion mmerụ ahụ.
Obi mgbawa: N'ime ndị ọrịa nwere nkụda mmụọ, ọkwa Ghrelin na-ebelatakarị ma na-ejikọta ya na oke nkụda obi. Ịgbakwunye Ghrelin ma ọ bụ analogues ya nwere ike imeziwanye ọrụ obi na ndị ọrịa nkụda mmụọ site n'ịkwalite myocardial contractility, imeziwanye ike nke obi obi, na igbochi apoptosis cell myocardial, si otú ahụ na-eme ka ndụ ndị ọrịa dịkwuo mma na ọnụego ndụ.
Ọrịa Neurodegenerative:
Ọrịa Alzheimer na Ọrịa Parkinson: Nyere Ghrelin si neuroprotective mmetụta, ọ na-ejide uru ngwa ngwa na ọgwụgwọ nke neurodegenerative ọrịa dị ka ọrịa Alzheimer na ọrịa Parkinson. Site na iji Ghrelin ma ọ bụ analogues ya, ọ nwere ike igbochi apoptosis neuronal, belata nzaghachi neuroinflammatory, ma melite ọrụ ọgụgụ isi na moto nke ndị ọrịa.
Ọrịa strok na mmerụ ahụ ụbụrụ: N'ime nnukwu mmerụ ahụ akwara dị ka ọrịa strok na mmerụ ahụ ụbụrụ, Ghrelin nwere ike ịkpata mmetụta neuroprotective site na usoro gụnyere ibelata mmebi neuronal na ịkwalite mmeghari akwara. Nnyocha egosiwo na n'ụdị anụmanụ nke ọrịa strok ma ọ bụ mmerụ ahụ ụbụrụ na-akpata, iji Ghrelin nwere ike ibelata ogo infarct ma ọ bụ belata oke mmebi ụbụrụ, si otú ahụ na-eme ka ọrụ nke akwara ozi dịkwuo mma. Ghrelin nwere ike bụrụ ọgwụgwọ mgbakwunye maka ọrịa strok na mmerụ ahụ ụbụrụ, na-eme ka nsonaazụ mweghachi nke ndị ọrịa na-aga n'ihu.
Mkpebi
Dị ka peptide multifunctional endogenous, Ghrelin na-arụ ọrụ dị mkpa na usoro physiological dị iche iche, gụnyere uto na mmepe, ike metabolism, ọrụ eriri afọ, usoro obi obi homeostasis, na neuroprotection.
Isi mmalite
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[4] Brahmkhatri V, Prasanna C, Atreya H. Insulin-dị ka Sistemụ Ihe Na-akpata Uto na Ọrịa Cancer: Usoro ọgwụgwọ Ezubere Ezubere [J]. Biomed Research International, 2014,2015.DOI:10.1155/2015/538019.
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