Site na Cocer Peptides 
ụbọchị 23 gara aga
Edemede na ozi ngwaahịa niile 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.
Ịka nká, dị ka usoro okike a na-apụghị izere ezere n'ime ihe ndị dị ndụ, abụwo ogologo oge isi ihe nyocha sayensị. Ka ihe ndị dị ndụ na-akawanye nká, mkpụrụ ndụ na-eji nwayọọ nwayọọ na-abanye n'ọnọdụ mmetụta uche, na nchịkọta nke mkpụrụ ndụ ndị a nwere ike imetụta ọrụ nkịtị nke anụ ahụ na akụkụ ahụ, na-ebute ọrịa dị iche iche metụtara afọ. FOX04 - DRI bara uru maka ikpochapụ mkpụrụ ndụ senescent.
Nchịkọta
DSIP peptide, Delta-Sleep-Inducing Peptide, bụ ihe na-achịkwa peptide bio-regulator neuro-regulatory. Ọ na-akwalite nhazi ụra. Tụkwasị na nke ahụ, ọ na-emetụta usoro okpomọkụ nke ahụ, ọnụ ọgụgụ obi, ọbara mgbali elu, ọnụ ụzọ mgbu, na usoro ihe na-akpata lymphatic, na mmetụta ndị a na-egosipụta ịdabere n'ụda circadian.
Usoro nke Omume nke DSIP Peptide na Ụra
Iwu Neurotransmitter
5-Hydroxytryptamine (5-HT): 5-HT bụ neurotransmitter dị mkpa nke jikọtara ya na nhazi ụra. Na steeti ehighị ụra nke ọma, dị ka ụdị ụra nke PCPA kpatara, ọkwa 5-HT na-ebelata nke ukwuu. Nnyocha na-egosi na peptides DSIP nwere ike ịbawanye ọkwa 5-HT na anụ ahụ hippocampal, si otú ahụ meziwanye ụra. 5-HT nwere ike ịchịkwa excitability neuronal site n'ime ihe dị iche iche subtypes nnabata, si otú na-emetụta na-ehi ụra okirikiri okirikiri. Ndị na-anabata 5-HT1A agonists nwere ike ịkwalite ụra anya na-adịghị ngwa ngwa (NREM), ebe ndị na-anabata 5-HT2A nwere ike ibelata oge ịmụrụ anya, ma nwekwuo oge ụra zuru ezu. DSIP peptides nwere ike itinye mmetụta nchịkwa ha na ụra site n'ịgbanwe ntọhapụ, reuptake, ma ọ bụ mmekọrịta ya na ndị nabatara 5-HT.
Dopamine (DA): Dopamine na-arụkwa ọrụ dị mkpa na nhazi ụra. N'okpuru ọnọdụ nkịtị, ọrụ nke neurons dopaminergic na-enye aka na ịnọgide na-amụ anya. Enweghị ahaghị nhata na ọkwa dopamine nwere ike ibute nsogbu ihi ụra. N'ụdị ụfọdụ nke ehighị ụra nke ọma, ọkwa dopamine na-ebelata, na peptides DSIP nwere ike iweghachi ọkwa dopamine n'otu akụkụ. Dopamine na-achịkwa akara akwara site na ijikọ ndị na-anabata dopamine dị iche iche. DSIP peptides nwere ike imeziwanye ụra site na imetụta ọrụ nke neurons dopaminergic, na-achịkwa njikọ dopamine, ntọhapụ, ma ọ bụ metabolism. Ọ nwere ike ime ihe na enzymes ndị dị mkpa na-etinye aka na nchịkọta dopamine, dị ka tyrosine hydroxylase, na-emetụta ọnụego nke dopamine njikọ ma si otú ahụ na-emetụta nguzozi nke ụra.
Glutamate (Glu): Glutamate bụ isi neurotransmitter na-akpali akpali na sistemụ ụjọ. N'oge ehighi ura, ọkwa glutamate nwere ike gbanwee. Nnyocha sayensị achọpụtala na peptides DSIP nwere ike ịhazi ọkwa glutamate na anụ ahụ hippocampal, na-abawanye ọkwa glutamate belata na ụdị ụfọdụ. Glutamate na-achịkwa excitability neuronal site na ijikọ ndị na-anabata ionotropic na metabotropic glutamate. DSIP peptides nwere ike idowe nguzozi ike nke neuronal site na ịhazi ọrụ nnabata glutamate ma ọ bụ na-emetụta ntọhapụ glutamate na usoro nnabata, si otú ahụ na-enwe mmetụta dị mma na ụra. Ha nwere ike gbanwee ọrụ nke ndị na-ebu glutamate iji chịkwaa mkpokọta glutamate extracellular, na-egbochi oke ma ọ bụ ezughi oke na-emetụta ụra.
Melatonin (MT): Melatonin bụ amine hormone zoro ezo site na pineal gland nke na-arụ ọrụ dị mkpa n'ịhazi usoro ụra ụra. N'ụdị oke nke ehighị ụra nke ọma, ọkwa melatonin dị na hippocampus belatara nke ukwuu, yana peptide DSIP nwere ike ịbawanye ọkwa melatonin. Melatonin na-achịkwa rhythm circadian na ụra site na ijikọ ndị na-anabata MT1 na MT2. DSIP nwere ike itinye mmetụta nchịkwa ya na ụra site na imetụta njikọ melatonin na nzuzo na gland pineal, ma ọ bụ site n'ịgbanwe okwu na ọrụ nke ndị na-anabata melatonin. Ọ nwere ike ịhazi ọrụ nke isi enzymes na-etinye aka na njikọ nke melatonin, dị ka aromatase N-acetyltransferase (AANAT), si otú ahụ na-emetụta ọkwa njikọ melatonin.
Ọgụgụ 2 Nkwuwapụta FOXO4 n'ime ule ụmụ mmadụ chọpụtara site na ntụpọ immunofluorescent.
Mmetụta na sel neuronal
N'ime ụdị oke ehighị ụra nke ọma na PCPA kpatara, Nchacha HE kpughere na oke otu ụdị ahụ gosipụtara oghere intercellular dị ntakịrị, nha sel pere mpe, morphology na-adịghị ahụkebe, na matriks rụrụ arụ na anụ ahụ hippocampal. N'ụzọ dị iche, otu peptide DSIP na-agwọ ọrịa (dị ka peptide ụra jikọtara ya na otu peptide cell-penetrating P-DSIP) gosipụtara mbelata oghere intercellular, nhazi sel ndị a na-enye iwu, na nkesa otu n'ime anụ ahụ hippocampal. Nke a na-egosi na DSIP peptide nwere ike imeziwanye mmebi nke ụra na-akpata na neurons hippocampal, na-edobe ọdịdị ọdịdị ha na nhazi ha, si otú ahụ hụ na ọrụ physiological ha na-emekarị, ma na-eme ka nhazi ụra dị mfe. Ọdịdị nkịtị nke neurons bụ ntọala maka mgbasa ozi akwara ozi na ntinye aka. Mmetụta nchebe nke DSIP peptide na sel neuronal nwere ike inye aka weghachite ọrụ nkịtị nke ụzọ akwara ozi metụtara nhazi ụra.
DSIP peptides nwere ike imetụta ọrụ electrophysiological neuronal. Neurons na-ebunye ozi site n'ịmepụta ikike ime ihe, na usoro ọrụ eletriki nke neuron na-agbanwe n'oge ụra. DSIP peptides nwere ike na-ahazi ọwa ion na membranes cell neuronal, na-agbanwe nhụsianya neuronal na ịgba egbe, si otú ahụ na-emetụta ọnọdụ ụra. Ha nwere ike ịkwalite ọrụ ụfọdụ ọwa potassium ion, na-eme ka neurons dịkwuo mfe ịbanye n'ọnọdụ izu ike na ịkwalite mmalite nke ụra.
Usoro metụtara mgbochi ụbụrụ ọbara
Ihe mgbochi ụbụrụ ọbara (BBB) bụ ihe mgbochi dị mkpa n'etiti ọbara na anụ ahụ ụbụrụ, na-egbochi ntinye nke ọtụtụ ihe sitere na ọbara banye n'anụ ahụ. Metabolism nke peptides DSIP na mgbochi ụbụrụ ụbụrụ bụ aminopeptidases na-eme ka ọ dị elu. N'ime ụbụrụ ụbụrụ ụbụrụ microvascular endothelial (BBMEC, ụdị mgbochi ụbụrụ ọbara), peptidyl dipeptidase A nwekwara ike metabolize DSIP site n'usoro hydrolyzing dipeptides ma ọ bụ tripeptides site na njedebe carboxy nke nonapeptide a. Site n'ịgbakwụnye peptidyl dipeptidase A inhibitors (dị ka captopril) na aminopeptidase inhibitors (dị ka besartan), DSIP metabolism na BBMEC nwere ike kwụsie ike kpamkpam, na-egosi na site n'ịchịkwa ọrụ nke ndị a enzymes, ọzọ DSIP peptides nwere ike gafere ọbara-ụbụrụ mgbochi na iru ụbụrụ ha na-ehi ụra anụ. Otu ọmụmụ nwara ijikọ peptides DSIP na peptides nwere ike ịgafe mgbochi ụbụrụ ọbara (dị ka CBBBP) iji mepụta peptides DSIP-CBBBP fusion. Ngwakọta peptides ndị a nwere ike ịhazi ọkwa neurotransmitter nke ọma, dị ka 5-HT, glutamate, dopamine, na melatonin, na-ebute mmetụta dị mma na imeziwanye ụra. Site n'ịkwalite ikike nke peptides DSIP ịgafe mgbochi ụbụrụ ọbara, enwere ike ịkwalite mmetụta ha na-achịkwa n'ụra.
Ọrụ DSIP peptides na-emeziwanye ụra
1. Ịbawanye oge ụra zuru oke
N'ime nnwale anụmanụ, peptides DSIP gosipụtara ikike ịbawanye oge ihi ụra n'anụmanụ, n'agbanyeghị ma a na-enye ya site na intravenous ma ọ bụ ụzọ imi. N'ime nnwale na oke bekee na-acha ọcha nke New Zealand, ịgba ọgwụ mgbochi DSIP peptides butere mmụba dị ukwuu na oge ụra zuru oke ma e jiri ya tụnyere otu njikwa saline. Nlekọta intranasal dịkwa irè, yana otu intranasal nke oke bekee ọcha nke New Zealand na-egosipụta ogologo oge ụra zuru oke karịa otu saline. Nke a na-egosi na DSIP peptide nwere ike ịkwalite mmalite nke ihi ụra n'anụmanụ ma nọgide na-ehi ụra ogologo oge. Mmụba oge ụra zuru oke dị oke mkpa maka mgbake anụ ahụ yana idobe ọrụ physiological nkịtị, ebe ọ na-enye ohere akụkụ ahụ na sistemu niile zuru ike nke ọma, na-enyere aka nrụzi anụ ahụ, usoro endocrine usoro na usoro ndị ọzọ.
N'ụdị oke ekpughere hypoxia na-adịghị ala ala (HH), ntinye aka na DSIP peptide phosphorylated (p-DSIP) ka enyere. Dabere na nsonaazụ ya, p-DSIP kwalitere ụra anya mmegharị anya na-adịghị ngwa ngwa (NREM) na ụra mmegharị anya ngwa ngwa (REM) na oke, na-abawanye oge ụra zuru oke. Nke a na-egosi na DSIP peptide na-akwalite ụra n'ofe ọnọdụ ihi ụra dị iche iche, na-eme ka usoro ihi ụra dịkwuo mma na ịkwalite ogo ụra.
2. Na-agbatị oge ụra na-adịghị nwayọọ
Ụra na-agba nwayọọ nwayọọ (SWS), nke a makwaara dị ka ụra miri emi, dị oké mkpa maka mgbake na nrụzi ahụ. DSIP peptide n'ụzọ dị ukwuu na-agbatị ogologo oge ụra na-adịghị nwayọọ n'ime anụmanụ. N'ime nnwale na oke bekee ọcha nke New Zealand, ma nchịkwa intravenous na intranasal nke DSIP mere ka ogologo oge ihi ụra na-adị ogologo oge n'ime ìgwè a na-emeso ya ma e jiri ya tụnyere ndị na-achịkwa saline. N'oge ihi ụra nke na-adịghị ngwa ngwa, ọnụego metabolic na-ebelata, na ihe omume physiological dị ka ọnụọgụ obi na iku ume na-ebelata, na-enye ahụ ahụ ohere itinye aka na nhazi onwe ya na nchekwa ike. DSIP peptides nwere ike ịgbatị oge ihi ụra nke na-adịghị nwayọọ, si otú a na-eme ka ahụ nwee ike mgbake, na-ebelata ike ọgwụgwụ, na-ewusi ike nchebe.
Site n'echiche neurobiological, DSIP peptides nwere ike ịhazi ọkwa neurotransmitter, mụbaa ọkwa 5-HT na melatonin, ma gbochie oke mkpali neuronal na ụbụrụ, si otú ahụ na-akwalite mmalite na mmezi nke ụra nwayọọ nwayọọ. Mmetụta nchebe ya na sel neuronal, na-edobe usoro ha na ọrụ ha, na-enyekwa aka n'ịmepụta gburugburu ebe obibi na-eme ka ụra dị nwayọọ.
3. Imelite omume metụtara ụra
N'ime nnwale omume, dị ka ule oghere oghere, nnwale elu gbakwunyere maze, na ule nkwusioru ọdụ, peptides DSIP gosipụtara mmụba dị ịrịba ama na arụmọrụ omume nke anụmanụ na-ehi ụra. N'ime ule n'ọhịa mepere emepe, oke ndị otu ụdị gosipụtara mbelata nke ukwuu ije ije na oge ọrụ, ebe oke a na-emeso ya na peptide DSIP (dịka ọmụmaatụ, otu P-DSIP) gosipụtara mmụba dị oke anya ije na oge ọrụ, na-egosi na DSIP peptide nwere ike imeziwanye ikike ọrụ nke oke ehighị ụra nke ọma ma belata mgbochi ọrụ kpatara nke ehighị ụra nke ọma kpatara. N'ime ule dị elu gbakwunyere maze, ọnụ ọgụgụ nke oge ụmụ oke ndị nlereanya na-abanye na ogwe aka mepere emepe na oge a na-etinye na ogwe aka mepere emepe belatara nke ukwuu. Otú ọ dị, mgbe nchịkwa nke DSIP peptide, dị ka n'ime ìgwè P-DSIP, ọnụ ọgụgụ nke oge ndị oke na-abanye na ogwe aka na-emeghe na oge a na-etinye na oghere oghere na-abawanye nke ukwuu, na-egosi na DSIP peptide nwere ike imeziwanye nchekasị-dị ka omume na oke ehighị ụra nke ọma. N'ime ule nkwusioru ọdụ, oke oke ndị nlereanya gosipụtara mmụba dị ukwuu na oge enweghị ike imegharị na mbelata dị ukwuu na oge mgba. Otú ọ dị, mgbe nchịkwa nke DSIP peptide (dị ka GABA otu, P-DSIP otu, na DSIP otu), oke gosiri mbelata dị ukwuu na oge na-adịghị na-arụ ọrụ na nnukwu mmụba nke oge mgba, na-egosi na DSIP peptide nwere ike imeziwanye ịda mbà n'obi-dị ka omume na-ehi ụra oke. DSIP peptide nwere ike melite okwu mmetụta uche na nke omume nke ehighị ụra nke ọma kpatara.
Ngwa nke DSIP Peptide na Iwu Ụra
Na nyocha ụlọ ọgwụ, na ụfọdụ nyocha ụlọ ọgwụ dị ntakịrị, mgbe o nyechara usoro DSIP peptide metụtara ndị ọrịa ehighị ụra nke ọma, ogo ihi ụra nke ụfọdụ ndị ọrịa mere ka ọ dịkwuo ogo dị iche iche, dị ka obere oge mmalite ihi ụra, ịba ụba ụra, na ibelata ụra abalị. Na mgbakwunye, enwere ike iji DSIP peptide naanị maka ọgwụgwọ ehighị ụra nke ọma ma ọ bụ yana yana ọgwụ ihi ụra ọdịnala ndị ọzọ. Nnyocha na-egosi na mgbe ejikọtara ya na ụfọdụ ọgwụ anxiolytic ma ọ bụ antidepressant, DSIP peptides na-egosipụta mmetụta synergistic, na-emeziwanye ogo ụra nke ndị ọrịa na ọnọdụ mmetụta uche. Mgbe ejiri ya na benzodiazepines, DSIP peptides nwere ike ibelata usoro onunu ogwu nke benzodiazepines, belata ihe ize ndụ nke mmeghachi omume ọjọọ, ma kwalite nrụpụta ọgwụgwọ.
Mmechi
Dị ka onye na-ahụ maka ihi ụra eke, DSIP peptide na-egosipụta ịdị irè na usoro nhazi ụra, mmetụta nkwalite ụra, na akụkụ ngwa.
Isi mmalite
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[2] Roy K, Chauhan G, Kumari P, et al. Phosphorylated delta sleeping peptide na-eweghachi ebe nchekwa ohere na okwu p-CREB site na imeziwanye ihe owuwu ụra na elu elu[J]. Ndụ sayensị, 2018,209:282-290.DOI:10.1016/j.lfs.2018.08.026.
[3] Augustijns PF, Ng KY, Williams TM, et al. Peptidyl dipeptidase A-catalyzed metabolism nke delta ụra na-akpali peptide n'ime ụbụrụ ụbụrụ microvessel endothelial sel: usoro omenala cell nke mgbochi ụbụrụ ọbara [J]. Nkwukọrịta nyocha nke biochemical na Biophysical, 1995,210(3):987-994.DOI:10.1006/bbrc.1995.1754.
[4] Yehuda S, Carasso R L. DSIP - ngwá ọrụ maka nyocha usoro mmalite ụra: nyocha [J]. Akwụkwọ akụkọ International nke Neuroscience, 1988,38 (3-4): 345-353.DOI: 10.3109/00207458808990695.
[5] Obál FJ, Kovalzon VM, Kalkevich VN, et al. Mmekọrịta-mmekọrịta ihe nhazi na mmetụta nke delta-ụra na-ebute peptide (DSIP) na ụra oke[J]. Pharmacology Biochemistry na Omume, 1986,24(4):889-894.DOI:10.1016/0091-3057(86)90432-6.
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