By Cocer Peptides 
Watanni 1 da suka gabata
DUKKANIN LABARI DA BAYANIN KYAUTATAWA DA AKE BAYAR A WANNAN SHAFIN KAWAI DOMIN WATSA BAYANI NE DA MANUFOFIN ILIMI.
Kayayyakin da aka bayar akan wannan gidan yanar gizon an yi niyya ne kawai don binciken in vitro. Binciken in vitro (Latin: *a cikin gilashi*, ma'ana a cikin gilashin gilashi) ana gudanar da shi a wajen jikin mutum. Waɗannan samfuran ba magunguna ba ne, Hukumar Abinci da Magunguna ta Amurka (FDA) ba ta amince da su ba, kuma dole ne a yi amfani da su don hanawa, magani, ko warkar da duk wani yanayi na likita, cuta, ko cuta. Doka ta haramta shigar da waɗannan samfuran cikin jikin mutum ko dabba ta kowace hanya.
Dubawa
Tun lokacin da aka gano shi a cikin 1999, ghrelin ya fito a matsayin cibiyar bincike a cikin ilimin kimiyyar rayuwa saboda keɓaɓɓen ayyukan ilimin halittar jiki da kuma tasirin ilimin halitta. Ghrelin yana taka muhimmiyar rawa wajen daidaita sakin hormone girma (GH) kuma yana da hannu a cikin mahimman hanyoyin ilimin lissafi da yawa, gami da ma'aunin makamashi, tsarin ci, aikin gastrointestinal, homeostasis na zuciya da jijiyoyin jini, da neuroprotection.
Hoto na 1 Ghrelin hormone a cikin nau'insa mara aiki (desacyl ghrelin) an canza shi zuwa nau'in aikinsa (acyl ghrelin).
Tsarin da Rarraba Ghrelin
(1) Tsari
Haɗin Sinadarin: Ghrelin polypeptide ne wanda ya ƙunshi amino acid 28, tare da tsarinsa na farko yana nuna babban kiyayewa a cikin nau'ikan nau'ikan daban-daban. A cikin mutane, jerin amino acid na ghrelin shine GSSFLSPEHQRVQQRKESKKPPAKLQPR. Siffar sa ta musamman ita ce gyare-gyaren octanoylation akan ragowar serine a matsayi na 3, wanda ke da mahimmanci don ɗaurin ghrelin ga mai karɓar hormone mai sakin hormone mai girma (GHS-R) da ƙoƙarin aikinsa na nazarin halittu.
Isomers: Baya ga classic octanoylated Ghrelin, akwai kuma Ghrelin deacetylated da sauran isomers. Kodayake Ghrelin deacetylated ba shi da gyare-gyaren octanoylation kuma ba shi da ikon ɗaure GHS-R tare da babban alaƙa, bincike ya nuna cewa yana iya yin tasirin ilimin halitta ta hanyar wasu masu karɓa ko hanyoyin da ba a sani ba.
(2) Rarrabawa
Rarraba nama: Ghrelin an haɗa shi da farko kuma an ɓoye shi ta sel masu ɓoye acid a cikin glandan fundic na ciki kuma ana bayyana shi a cikin kyallen takarda da gabobin da yawa, gami da ƙananan hanji, pancreas, hypothalamus, da glandan pituitary. A cikin sashin gastrointestinal, matakan magana na ghrelin suna raguwa a hankali daga ciki zuwa ƙananan hanji. A cikin tsarin kulawa na tsakiya, ghrelin yana bayyana sosai a cikin yankuna irin su arcuate nucleus da paraventricular nucleus na hypothalamus, waɗanda ke da alaƙa da tsarin ci abinci, makamashi na makamashi, da tsarin neuroendocrine.
Ƙwararren ƙwayar cuta: A cikin ciki, Ghrelin an bayyana shi da farko a cikin kwayoyin endocrin na mucosa na ciki, wanda zai iya gano yanayin abinci mai gina jiki a cikin gastrointestinal tract kuma ya watsa sigina zuwa tsarin juyayi na tsakiya ta hanyar ɓoyewar Ghrelin. A cikin glandar pituitary, Ghrelin na iya yin aiki kai tsaye akan ƙwayoyin hormone girma don daidaita sakin hormone girma.
Tsarin Ayyukan Ci gaban Hormone-Sakin Peptide
(1) Daure ga masu karba
Hanyar sigina mai tsaka-tsaki ta GHS-R: Babban tasirin ilimin halitta na Ghrelin yana samuwa ta hanyar ɗaure ga mai karɓar hormone mai sakin hormone 1a (GHS-R1a). GHS-R1a mai karɓa ne mai haɗin furotin G wanda aka rarraba a cikin glandar pituitary, hypothalamus, da sauran kyallen takarda. Bayan ɗaure zuwa GHS-R1a, ghrelin yana kunna sunadaran G, wanda hakanan yana kunna phospholipase C (PLC) -inositol trisphosphate (IP3) - hanyar siginar siginar ion (Ca⊃2; ⁺) hanyar siginar siginar, yana haifar da haɓakar Ca⊃2 na intracellular;
Hanyoyin da ba GHS-R ba: Baya ga GHS-R1a, bincike ya nuna cewa ghrelin na iya yin tasirin ilimin halitta ta hanyar hulɗa tare da wasu masu karɓa ko sunadarai na membrane.
Hoto 2 Ghrelin yana yin tasirin sa a cikin hypothalamus ta hanyoyi daban-daban guda uku.
(2) Ka'idar magana ta kwayoyin halitta
Hypothalamic-pituitary axis-genes: Ghrelin na iya daidaita maganganun kwayoyin halitta da yawa a cikin axis hypothalamic-pituitary. A matakin pituitary, ghrelin na iya daidaita fassarar kwayar halittar hormone girma, inganta haɓakawa da sakin hormone girma. A cikin hypothalamus, ghrelin zai iya rinjayar bayyanar hormone mai sakin hormone girma (GHRH) da somatostatin (SS), a kaikaice yana daidaita sakin hormone girma ta hanyar daidaita siginar GHRH da SS. Musamman, ghrelin na iya tayar da siginar GHRH yayin da yake hana ɓarnar SS, ta haka yana haɓaka sakin hormone girma.
Kwayoyin da ke da alaƙa da makamashi na makamashi: A cikin adipose nama da hanta, ghrelin yana sarrafa maganganun kwayoyin halittar da ke da alaƙa da makamashin makamashi. Alal misali, ghrelin na iya haɓaka maganganun mai karɓar mai karɓa na peroxisome proliferator γ (PPARγ), yana inganta bambancin adipocyte da lipogenesis; a lokaci guda, a cikin hanta, ghrelin yana sarrafa bayanin kwayoyin halittar da ke da alaƙa da gluconeogenesis, yana rinjayar homeostasis na matakan glucose na jini.
Tasirin jiki na peptide mai sakin hormone girma
(1) Inganta sakin hormone girma
Ayyukan kai tsaye a kan glandar pituitary: Ghrelin wani wakili ne mai girma na haɓakar hormone wanda ke aiki kai tsaye a kan kwayoyin hormone girma a cikin glandar pituitary na gaba, yana inganta haɓakawa da sakin hormone girma ta hanyar GHS-R1a-tsakanin hanyar sigina. Idan aka kwatanta da girma hormone-sakin hormone (GHRH), ghrelin stimulates girma hormone saki da sauri, kuma biyu suna da synergistic effects. A ƙarƙashin yanayin ilimin lissafi, ghrelin, GHRH, da somatostatin tare suna daidaita siginar bugun jini na hormone girma, suna kiyaye matakan hormone girma na al'ada.
Tasiri kan girma: hormone girma yana taka muhimmiyar rawa wajen inganta ci gaban jiki da ci gaba. Ghrelin a kaikaice yana rinjayar girma ta hanyar haɓaka sakin hormone girma. A lokacin ƙuruciya da samartaka, ɓoyayyun Ghrelin na yau da kullun yana da mahimmanci ga matakai kamar haɓakar kwarangwal da haɓakar tsoka. A cikin marasa lafiya da ƙarancin girma na hormone, matakan ɓoye na ghrelin sau da yawa suna da ƙasa. Exogenous gudanarwa na ghrelin ko analogues na iya haɓaka matakan girma girma da haɓaka haɓaka da haɓaka yadda ya kamata.
(2) Ka'idojin Metabolism na Makamashi
Dokokin Ci abinci: Ghrelin, wanda aka sani da 'hormone na yunwa,' muhimmin kwayar sigina ce mai daidaita ci. A cikin arcuate nucleus na hypothalamus, ghrelin yana ɗaure ga masu karɓar GHS-R1a akan neuropeptide Y (NPY) / furotin da ke da alaƙa (AgRP) neurons, yana ƙarfafa sakin NPY da AgRP, ta haka yana haɓaka ci da haɓaka ci abinci. Ghrelin kuma a kaikaice yana rinjayar ci ta hanyar daidaita ayyukan corticotropin-releasing hormone (CRH) neurons a cikin tsakiya na tsakiya na hypothalamus. A lokacin azumi, matakan ghrelin suna tashi, yana haifar da yunwa; bayan cin abinci, matakan ghrelin suna raguwa da sauri, yana inganta jin dadi.
Tsarin ma'auni na makamashi: Ghrelin kuma yana shiga cikin tsarin sarrafa kuzarin makamashi, yana kiyaye ma'aunin kuzarin jiki. Ghrelin yana haɓaka lipolysis, yana ƙara yawan iskar oxygen, kuma yana haɓaka samar da kuzarin jiki. Ghrelin yana hana fitowar insulin, yana rage ɗaukar nama na gefe da amfani da glucose, kuma yana haɓaka matakan glucose na jini, yana ba da jiki ƙarin hanyoyin makamashi. Babban bayyanar da ghrelin na yau da kullun na iya haifar da yawan kuzarin kuzari, tara mai, da rikicewar rayuwa kamar kiba.
(3) Tasiri kan aikin gastrointestinal
Sirrin acid na ciki da motsin ciki: A cikin sashin gastrointestinal, ghrelin yana taka muhimmiyar rawa wajen daidaitawa a cikin ɓoyewar acid na ciki da motsin ciki. Ghrelin yana motsa ƙwayoyin mucosal na parietal na ciki don ɓoye acid na ciki, yana daidaita yanayin acidic a cikin ciki, wanda ke taimakawa cikin narkewar abinci da sha. Ghrelin yana haɓaka peristalsis na gastrointestinal, yana haɓaka motsin motsa jiki a cikin sashin gastrointestinal kuma yana hanzarta fitar da abinci daga sashin gastrointestinal. A wasu cututtuka na ciki, irin su dyspepsia na aiki da gastroparesis, ƙananan matakan Ghrelin na iya haifar da rushewa a cikin ɓoyewar acid na ciki da motsin ciki.
Kariya na Mucosa na Gastrointestinal: Ghrelin yana da tasirin kariya akan mucosa na ciki. Yana inganta haɓakawa da gyaran ƙwayoyin mucosal na ciki, yana haɓaka aikin shinge na mucosal, da kare kariya daga lalacewa daga abubuwa masu cutarwa irin su gastric acid da Helicobacter pylori. A cikin nau'ikan cututtuka irin su ulcers na ciki da duodenal ulcers, exogenous gudanarwa na ghrelin yana hanzarta warkar da miki kuma yana rage girman lalacewar mucosal.
(4) Tsarin tsarin tsarin zuciya
Ka'idojin aikin zuciya: Ghrelin an bayyana shi sosai a cikin zuciya kuma yana taka muhimmiyar rawa wajen daidaita aikin zuciya. Ghrelin yana haɓaka ƙaƙƙarfan ƙwayar zuciya, yana haɓaka fitarwar zuciya, kuma yana haɓaka aikin bugun zuciya. A cikin nau'ikan rauni na ischemia-reperfusion na myocardial, ghrelin yana rage apoptosis na cell myocardial apoptosis da necrosis, yana rage girman infarct, kuma yana yin tasiri na zuciya. Tsarinsa na iya kasancewa yana da alaƙa da kunna hanyoyin siginar rayuwa ta ciki, kamar hanyar siginar phosphoinotide 3-kinase (PI3K)/protein kinase B (Akt).
Ka'idojin Tension na Vascular: Ghrelin yana daidaita tashin hankali na jijiyoyin jini kuma yana kiyaye tsayayyen hawan jini. Yana aiki akan ƙwayoyin tsoka mai santsi na jijiyoyi don hana tasirin abubuwan vasoconstrictive kamar angiotensin II, haifar da vasodilation, rage juriya na jijiyoyin bugun jini, kuma ta haka yana rage karfin jini. Har ila yau, Ghrelin yana hana maganganun ƙwayoyin ƙwayoyin ƙwayoyin ƙwayoyin ƙwayoyin ƙwayoyin ƙwayoyin ƙwayoyin ƙwayoyin ƙwayoyin ƙwayoyin ƙwayoyin cuta, suna rage mannewa da kutsawa na ƙwayoyin kumburi, suna yin tasirin kariya na jijiyoyin jini, da hana ci gaban atherosclerosis.
(5) Tasirin Neuroprotective
Rayuwar Neuronal da Yaduwa: A cikin tsarin juyayi, ghrelin yana da tasiri mai kariya akan ƙwayoyin cuta. Yana haɓaka haɓakawa da bambance-bambancen ƙwayoyin jijiyoyi na jijiyoyi, yana ƙara yawan ƙwayoyin ƙwayoyin cuta, kuma yana kula da ci gaba na al'ada da aiki na tsarin jijiya. A cikin samfuran cututtukan neurodegenerative kamar cutar Alzheimer da cutar Parkinson, ghrelin na iya hana apoptosis neuronal, rage martanin neuroinflammatory, da haɓaka fahimi da ayyukan motsa jiki. Hanyoyin sa na neuroprotective na iya kasancewa da alaƙa da daidaitawa na intracellular oxidative amsawa, hana hanyoyin siginar apoptosis, da inganta sakin masu watsawa.
Dokokin Neuroendocrine: A matsayin tsarin tsarin neuroendocrine, Ghrelin yana shiga cikin daidaita aikin hypothalamic-pituitary-adrenal axis (HPA axis). A ƙarƙashin yanayin damuwa, matakan ghrelin da aka ɗaukaka sun hana wuce kima kunnawa na axis na HPA, rage ƙwayar corticosteroid kuma ta haka yana rage lalacewar da ke haifar da damuwa ga jiki. Bugu da ƙari, ghrelin yana daidaita tsarin hypothalamic-pituitary-thyroid axis (HPT axis) da kuma hypothalamic-pituitary-gonadadal axis (HPG axis), yana kiyaye homeostasis na tsarin neuroendocrine.
(6) Sauran illolin jiki
Tsarin rigakafi: Ghrelin kuma yana taka rawa a cikin tsarin rigakafi. Yana iya daidaita aikin ƙwayoyin rigakafi, inganta haɓakawa da bambance-bambancen lymphocytes, da haɓaka ƙarfin amsawar jiki. A cikin jihohi masu kumburi, ghrelin na iya hana sakin cytokines mai kumburi, irin su ƙwayar cuta necrosis factor-α (TNF-α) da interleukin-6 (IL-6), don haka rage martani mai kumburi da kuma yin tasirin immunomodulatory da anti-mai kumburi.
Ka'idojin Metabolism na Kashi: Ghrelin yana da tasiri mai tasiri akan metabolism na kashi. Yana haɓaka haɓakawa da bambance-bambancen osteoblasts, yana hana ayyukan osteoclasts, don haka ƙara yawan kashi da haɓaka haɓakar ƙashi. A cikin marasa lafiya da osteoporosis, matakan ghrelin sau da yawa suna raguwa, yana nuna cewa ghrelin na iya haɗuwa da ci gaban osteoporosis. Exogenous gudanarwa na ghrelin ko analogues na iya ba da sabbin dabarun warkewa don osteoporosis.
Aikace-aikace na Ci gaban Hormone-Sakin Peptide
(1) Aikace-aikacen Magungunan Magunguna
Karancin Hormone na Ci gaban: Ga marasa lafiya da ƙarancin girma na hormone, Ghrelin da analogues ɗin sa na iya zama wakilai na warkewa. Ta hanyar haɓaka sakin hormone girma, suna haɓaka haɓaka da haɓaka a cikin marasa lafiya. Idan aka kwatanta da maganin maye gurbin hormone girma na al'ada, Ghrelin da analogues ɗin sa suna ba da mafi kyawun aminci da haƙuri, kuma suna iya haɓaka haɓaka ta hanyar da ta dace ta ilimin lissafi ta hanyar daidaita ɓoyayyun hormone girma na endogenous.
Hoto na 3 Tsarin Endocrine na GH da kuma toshewar warkewa.
Cututtukan Metabolic
Kiba da Ciwon sukari: A cikin maganin kiba, kodayake ana kiran Ghrelin a matsayin 'hormone na yunwa,' daidaita matakan Ghrelin ko hanyoyin siginar sa na iya inganta metabolism na makamashi, rage ci, da samun asarar nauyi. Haɓaka antagonists mai karɓar Ghrelin don toshe haɗin Ghrelin ga masu karɓa na iya hana ci da rage cin abinci. Ga masu ciwon sukari, Ghrelin na iya yin tasiri mai fa'ida akan matakan glucose na jini ta hanyoyi kamar daidaita ƙwayar insulin da haɓaka juriya na insulin. Exogenous gudanarwa na Ghrelin yana inganta sarrafa glucose na jini da kuma ji na insulin a cikin berayen masu ciwon sukari, yana ba da sabbin fahimta don maganin ciwon sukari.
Ciwon Metabolic: Ciwon Metabolic rukuni ne na cututtukan da ke da kiba, hauhawar jini, hyperglycemia, da dyslipidemia. Saboda rawar da yake takawa a cikin makamashin makamashi da tsarin tsarin zuciya, ghrelin na iya zama maƙasudin manufa don magance ciwo na rayuwa. Ta hanyar daidaita matakan ghrelin, yana iya yiwuwa a lokaci guda inganta alamun rashin lafiya na rayuwa a cikin marasa lafiya da ke fama da ciwo na rayuwa, kamar asarar nauyi, rage karfin jini, da haɓakawa a cikin glucose na jini da nakasar lipid.
Cututtukan Gastrointestinal:
Dyspepsia na aiki da gastroparesis: Ga marasa lafiya tare da dyspepsia na aiki da gastroparesis, ghrelin da analogues na iya inganta alamun narkewar abinci da haɓaka ɓarna na ciki ta hanyar haɓaka motsin ciki da haɓaka haɓakar acid na ciki. Yin amfani da analogues na ghrelin na iya sauƙaƙe alamun bayyanar cututtuka kamar ciwon ciki na sama da kumburi a cikin marasa lafiya da dyspepsia na aiki, ta haka inganta rayuwarsu.
Ciwon Gastrointestinal: Saboda tasirin kariya na Ghrelin akan mucosa na ciki, yana iya haɓaka warkar da gyambon ciki kuma yana da yuwuwar ƙimar aikace-aikacen a cikin maganin gyambon ciki. Exogenous gudanarwa na Ghrelin ko kwatankwacinsa na iya hanzarta aiwatar da gyaran gyambon ciki kuma ya rage komawar ulcer.
Cututtukan zuciya:
Myocardial ischemia-reperfusion rauni: A cikin jiyya na myocardial ischemia-reperfusion rauni, Ghrelin, saboda ta cardioprotective effects, rike alkawari a matsayin novel warkewa wakili. Ta hanyar gudanar da Ghrelin ko kwatankwacinsa kafin ko lokacin ischemia-reperfusion na myocardial, zai iya rage lalacewar ƙwayoyin cuta na zuciya, rage girman infarct, da haɓaka aikin zuciya. Gwaje-gwajen dabbobi da sakamakon gwaji na asibiti sun nuna sakamako mai ban sha'awa, suna ba da sababbin dabaru don magance raunin ischemia-reperfusion na zuciya.
Rashin gazawar zuciya: A cikin marasa lafiya tare da gazawar zuciya, matakan Ghrelin sau da yawa suna raguwa kuma suna daidaitawa da tsananin gazawar zuciya. Ƙarawa tare da Ghrelin ko kwatankwacinsa na iya inganta aikin zuciya a cikin marasa lafiya na gazawar zuciya ta hanyar haɓaka ƙarfin zuciya na zuciya, haɓaka ƙarfin kuzarin zuciya, da hana apoptosis cell myocardial, don haka haɓaka ingancin rayuwar marasa lafiya da ƙimar rayuwa.
Cututtukan Neurodegenerative:
Cutar Alzheimer da Cutar Parkinson: Idan aka ba da tasirin neuroprotective na Ghrelin, yana da ƙimar aikace-aikacen da za a iya amfani da shi a cikin maganin cututtukan neurodegenerative kamar cutar Alzheimer da cutar Parkinson. Ta hanyar gudanar da Ghrelin ko kwatankwacinsa, yana iya hana apoptosis neuronal, rage martanin neuroinflammatory, da haɓaka fahimi da ayyukan motsa jiki na marasa lafiya.
Stroke and Traumatic Brain Injury: In acute neurological injuries such as stroke and traumatic brain injury, Ghrelin may exert neuroprotective effects through mechanisms including reducing neuronal damage and promoting neural regeneration. Nazarin ya nuna cewa a cikin nau'ikan dabbobi na bugun jini ko raunin kwakwalwa mai rauni, amfani da Ghrelin na iya rage girman infarct ko rage girman lalacewar kwakwalwa, ta haka inganta sakamakon aikin jijiya. Ghrelin na iya zama magani na gaba don bugun jini da rauni na kwakwalwa mai rauni, yana kara haɓaka sakamakon dawo da marasa lafiya.
Ƙarshe
A matsayin peptide na endogenous multifunctional, Ghrelin yana taka muhimmiyar rawa a cikin matakai daban-daban na ilimin lissafin jiki, gami da haɓakawa da haɓakawa, haɓakar kuzari, aikin gastrointestinal, tsarin zuciya da jijiyoyin jini homeostasis, da neuroprotection.
Sources
[1] Basuny A, Aboelainin M, Hamed E. Tsarin da Ayyukan Jiki na Ghrelin[J]. Jaridar Biomedical na Binciken Kimiyya & Fasaha, 2020,31.DOI:10.26717/BJSTR.2020.31.005080.
[2] Ibrahim A M. Ghrelin - Ayyukan Jiki da Ka'ida [J]. Eur Endocrinol, 2015,11 (2):90-95.DOI:10.17925/EE.2015.11.02.90.
[3] Khatib N, Gaidhane S, Gaidhane AM, et al. Ghrelin: ghrelin a matsayin mai kula da Peptide a cikin haɓakar hormone girma. Journal of Clinical and Diagnostic Research : Jcdr, 2014,8 8: MC13-MC17. https://api.semanticscholar.org/CorpusID:25154124.
[4] Brahmkhatri V, Prasanna C, Atreya H. Insulin-Kamar Tsarin Ci gaban Ci gaban Ciwon Kankara: Novel Target Therapies[J]. Biomed Research International, 2014,2015.DOI:10.1155/2015/538019.
[5] Strasser F. Clinical aikace-aikace na ghrelin.[J]. Tsarin Magunguna na Yanzu, 2012,18 31:4800-4812. https://api.semanticscholar.org/CorpusID:7696286.
