Los ntawm Cocer Peptides 
23 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 laus, raws li cov txheej txheem ntuj tsim tsis tau hauv cov kab mob uas muaj sia nyob, tau ntev ua qhov tseem ceeb ntawm kev tshawb fawb tshawb fawb. Raws li cov kab mob muaj hnub nyoog, cov hlwb maj mam nkag mus rau hauv lub xeev senescent, thiab cov pob txha ntawm cov hlwb no tuaj yeem cuam tshuam tsis zoo rau kev ua haujlwm ntawm cov ntaub so ntswg thiab cov kabmob, ua rau muaj ntau yam kabmob ntsig txog hnub nyoog. FOX04 - DRI muaj txiaj ntsig zoo rau tshem tawm cov hlwb senescent.
Txheej txheem cej luam
DSIP peptide, Delta-Pleev-Inducing Peptide, yog ib qho neuro-regulatory peptide bio-regulator. Nws txhawb txoj cai pw tsaug zog. Tsis tas li ntawd, nws cuam tshuam rau lub cev kub tswj, lub plawv dhia, ntshav siab, qhov pib mob, thiab cov kab mob lymphatic, nrog rau cov teebmeem no qhia txog circadian atherosclerosis.
Mechanism of Action of DSIP Peptide on Sleep
Kev cai Neurotransmitter
5-Hydroxytryptamine (5-HT): 5-HT yog ib qho tseem ceeb neurotransmitter ze ze nrog kev tswj kev pw tsaug zog. Hauv cov xeev insomnia, xws li PCPA-induced insomnia qauv, 5-HT qib tau txo qis. Kev tshawb fawb qhia tias DSIP peptides tuaj yeem nce qib 5-HT hauv cov ntaub so ntswg hippocampal, yog li txhim kho kev pw tsaug zog. 5-HT tuaj yeem tswj hwm kev ua kom muaj zog neuronal los ntawm kev ua haujlwm ntawm ntau hom receptor subtypes, yog li cuam tshuam rau lub voj voog pw tsaug zog. 5-HT1A receptor agonists tuaj yeem txhawb nqa lub qhov muag tsis nrawm (NREM) pw tsaug zog, thaum 5-HT2A receptor antagonists tuaj yeem txo lub sijhawm pw tsaug zog, thiab ua kom tag nrho lub sijhawm pw tsaug zog. DSIP peptides tuaj yeem siv lawv cov kev tswj hwm ntawm kev pw tsaug zog los ntawm kev hloov kho qhov tso tawm, rov ua dua, lossis cuam tshuam nrog 5-HT receptors.
Dopamine (DA): Dopamine kuj ua lub luag haujlwm tseem ceeb hauv kev tswj kev pw tsaug zog. Hauv cov xwm txheej ib txwm muaj, kev ua haujlwm ntawm dopaminergic neurons pab txhawb kom muaj kev tsaug zog. Kev tsis sib haum xeeb hauv qib dopamine tuaj yeem ua rau pw tsaug zog tsis zoo. Hauv qee cov qauv insomnia, qib dopamine txo qis, thiab DSIP peptides tuaj yeem rov ua kom dopamine ib nrab. Dopamine tswj cov teeb liab neural los ntawm kev khi rau cov dopamine receptors sib txawv. DSIP peptides tuaj yeem txhim kho kev pw tsaug zog los ntawm kev cuam tshuam cov haujlwm ntawm dopaminergic neurons, tswj dopamine synthesis, tso tawm, lossis metabolism. Nws tuaj yeem ua rau cov enzymes tseem ceeb koom nrog hauv dopamine synthesis, xws li tyrosine hydroxylase, cuam tshuam tus nqi ntawm dopamine synthesis thiab yog li cuam tshuam rau kev pw tsaug zog-tsim tshuav nyiaj li cas.
Glutamate (Glu): Glutamate yog thawj excitatory neurotransmitter hauv nruab nrab paj hlwb. Thaum insomnia, qib glutamate tuaj yeem hloov pauv. Cov kev tshawb fawb tshawb fawb tau pom tias DSIP peptides tuaj yeem tswj cov qib glutamate hauv hippocampal cov ntaub so ntswg, nce qib glutamate hauv qee cov qauv. Glutamate tswj cov neuronal excitability los ntawm kev khi rau ionotropic thiab metabotropic glutamate receptors. DSIP peptides tuaj yeem tswj hwm qhov sib npaug ntawm neuronal excitability los ntawm kev tswj hwm glutamate receptor muaj nuj nqi lossis cuam tshuam rau glutamate tso tawm thiab cov txheej txheem uptake, yog li ua rau muaj txiaj ntsig zoo ntawm kev pw tsaug zog. Lawv tuaj yeem hloov kho cov kev ua ntawm glutamate transporters los tswj cov glutamate extracellular concentrations, tiv thaiv ntau dhau lossis tsis txaus los ntawm kev cuam tshuam rau kev pw tsaug zog.
Melatonin (MT): Melatonin yog amine hormone secreted los ntawm lub caj pas pineal uas ua lub luag haujlwm tseem ceeb hauv kev tswj lub voj voog pw tsaug zog. Hauv cov qauv nas ntawm kev pw tsaug zog, cov qib melatonin hauv hippocampus tau txo qis, thiab DSIP peptide tuaj yeem nce qib melatonin. Melatonin tswj lub circadian atherosclerosis thiab pw tsaug zog los ntawm kev khi rau MT1 thiab MT2 receptors. DSIP tuaj yeem siv nws cov kev tswj hwm ntawm kev pw tsaug zog los ntawm kev cuam tshuam melatonin synthesis thiab tso tawm hauv lub caj pas pineal, lossis los ntawm kev hloov kho qhov kev qhia thiab kev ua haujlwm ntawm melatonin receptors. Nws tuaj yeem tswj hwm cov haujlwm ntawm cov enzymes tseem ceeb koom nrog hauv melatonin synthesis, xws li aromatase N-acetyltransferase (AANAT), yog li cuam tshuam rau qib melatonin synthesis.
Daim duab 2 Kev nthuav qhia ntawm FOXO4 nyob rau hauv tib neeg cov tshuaj ntsuam xyuas los ntawm immunofluorescent staining.
Kev cuam tshuam rau cov hlwb neuronal
Nyob rau hauv PCPA-induced insomnia nas qauv, HE staining qhia tias cov qauv pab pawg nas nthuav tawm cov chaw sib cuam tshuam ntau ntxiv, cov xov tooj me me, tsis xwm yeem morphology, thiab xoob matrix hauv cov ntaub so ntswg hippocampal. Hauv qhov sib piv, DSIP peptide-kho pab pawg (xws li pw tsaug zog peptide ua ke nrog cell-peptide pab pawg P-DSIP) tau pom tias txo qis ntawm cov cellular, kev txiav txim ntau ntawm tes, thiab ntau yam kev faib tawm hauv cov ntaub so ntswg hippocampal. Qhov no qhia tias DSIP peptide tuaj yeem txhim kho kev pw tsaug zog vim kev puas tsuaj rau hippocampal neurons, tswj lawv cov morphology thiab cov qauv, yog li ua kom lawv lub cev muaj zog, thiab pab tswj kev pw tsaug zog. Cov qauv ntawm cov neurons ib txwm yog lub hauv paus rau neural teeb liab kis tau tus mob thiab kev koom ua ke. Kev tiv thaiv cov nyhuv ntawm DSIP peptide ntawm cov hlwb neuronal tuaj yeem pab rov ua haujlwm zoo ntawm cov kab mob neural ntsig txog kev tswj kev pw tsaug zog.
DSIP peptides tuaj yeem cuam tshuam kev ua haujlwm ntawm neuronal electrophysiological. Neurons xa cov ntaub ntawv los ntawm kev ua kom muaj peev xwm ua tau, thiab cov qauv hluav taws xob ntawm cov neurons hloov thaum pw tsaug zog. DSIP peptides tuaj yeem tswj cov ion raws ntawm cov cell membranes, hloov pauv neuronal excitability thiab firing zaus, yog li cuam tshuam rau cov xeev pw tsaug zog. Lawv tuaj yeem txhim kho kev ua haujlwm ntawm qee cov poov tshuaj ion channel, ua rau cov neurons nquag nkag mus rau lub xeev so thiab txhawb qhov pib ntawm kev pw tsaug zog.
Ntshav-hlwb barrier-txog mechanisms
Blood-brain barrier (BBB) yog ib qho kev cuam tshuam tseem ceeb ntawm cov ntshav thiab lub hlwb, txwv tsis pub nkag ntawm ntau yam ntawm cov ntshav mus rau hauv lub hlwb. Cov metabolism ntawm DSIP peptides ntawm cov ntshav-hlwb barrier yog catalyzed los ntawm aminopeptidases. Nyob rau hauv kab lis kev cai bovine hlwb microvascular endothelial hlwb (BBMEC, cov ntshav-hlwb barrier qauv), peptidyl dipeptidase A kuj tseem metabolize DSIP los ntawm sequentially hydrolyzing dipeptides los yog tripeptides los ntawm carboxy terminal ntawm no nonapeptide. Los ntawm kev ntxiv peptidyl dipeptidase A inhibitors (xws li captopril) thiab aminopeptidase inhibitors (xws li besartan), DSIP metabolism hauv BBMECs tuaj yeem ua kom ruaj khov, qhia tau hais tias los ntawm kev tswj hwm cov haujlwm ntawm cov enzymes, ntau DSIP peptides tuaj yeem hla cov ntshav-hlwb barrier thiab ncav cuag lawv lub hlwb kev cuam tshuam. Ib txoj kev tshawb nrhiav tau sim fuse DSIP peptides nrog peptides muaj peev xwm hla cov ntshav-hlwb teeb meem (xws li CBBBP) los tsim DSIP-CBBBP fusion peptides. Cov fusion peptides tuaj yeem tswj hwm cov qib neurotransmitter zoo dua, xws li 5-HT, glutamate, dopamine, thiab melatonin, ua rau muaj txiaj ntsig zoo rau kev txhim kho kev pw tsaug zog. Los ntawm kev ua kom zoo dua qhov muaj peev xwm ntawm DSIP peptides hla cov ntshav-hlwb teeb meem, lawv cov kev tswj hwm ntawm kev pw tsaug zog tuaj yeem txhim kho.
Lub luag haujlwm ntawm DSIP peptides hauv kev txhim kho kev pw tsaug zog
1. Ua kom tag nrho lub sijhawm pw tsaug zog
Hauv kev sim tsiaj, DSIP peptides tau pom tias muaj peev xwm ua kom tag nrho cov sij hawm pw tsaug zog hauv cov tsiaj, tsis hais seb puas siv los ntawm txoj hlab ntshav lossis qhov ntswg. Hauv kev sim nrog New Zealand dawb luav, kev txhaj tshuaj ntawm DSIP peptides ua rau muaj qhov nce ntxiv ntawm tag nrho cov sij hawm pw tsaug zog piv rau pawg tswj hwm saline. Intranasal kev tswj hwm tau zoo sib npaug, nrog rau cov pab pawg neeg intranasal ntawm New Zealand dawb luav nthuav tawm lub sijhawm pw tsaug zog ntev dua li pab pawg saline. Qhov no qhia tau hais tias DSIP peptide tuaj yeem txhawb qhov pib ntawm kev pw tsaug zog hauv cov tsiaj txhu thiab tswj kom lub sijhawm pw tsaug zog ntev. Ua kom tag nrho lub sijhawm pw tsaug zog yog qhov tseem ceeb rau lub cev rov qab los thiab kev saib xyuas ntawm lub cev lub cev, vim nws tso cai rau txhua lub cev thiab lub cev kom so kom txaus, pab kho cov ntaub so ntswg, kev tswj hwm endocrine, thiab lwm yam txheej txheem.
Hauv cov qauv nas raug rau cov mob tsis tshua muaj siab hypoxia (HH), kev cuam tshuam nrog phosphorylated DSIP peptide (p-DSIP) tau tswj hwm. Raws li cov txiaj ntsig, p-DSIP txhim kho qhov tsis pom qhov muag nrawm nrawm (NREM) thiab qhov muag nrawm nrawm (REM) hauv cov nas, nce tag nrho lub sijhawm pw tsaug zog. Qhov no qhia tau tias DSIP peptide txhawb kev pw tsaug zog thoob plaws lub xeev pw tsaug zog, txhim kho kev pw tsaug zog thiab txhim kho kev pw tsaug zog zoo.
2. Txuas lub sijhawm pw tsaug zog qeeb qeeb
Kev pw tsaug zog qeeb qeeb (SWS), tseem hu ua pw tsaug zog, yog qhov tseem ceeb rau lub cev rov qab los thiab kho. DSIP peptide txuas ntxiv qeeb-yoj pw tsaug zog ntev hauv cov tsiaj. Hauv kev sim nrog New Zealand dawb luav, ob leeg txhaj tshuaj thiab intranasal kev tswj hwm ntawm DSIP ua rau lub sijhawm pw tsaug zog qeeb qeeb hauv pawg kho mob piv rau pawg tswj hwm saline. Thaum lub sijhawm pw tsaug zog qeeb qeeb, tus nqi metabolic txo qis, thiab kev ua haujlwm ntawm lub cev xws li lub plawv dhia thiab ua pa qeeb, ua rau lub cev tuaj yeem kho tus kheej thiab lub zog cia. DSIP peptides tuaj yeem txuas ntxiv lub sijhawm pw tsaug zog qeeb, yog li ua kom lub cev rov qab muaj peev xwm, txo qhov qaug zog, thiab ntxiv dag zog rau kev tiv thaiv.
Los ntawm kev xav txog neurobiological, DSIP peptides tuaj yeem tswj hwm cov qib neurotransmitter, nce 5-HT thiab melatonin qib, thiab inhibit ntau cov neuronal excitation nyob rau hauv lub hlwb, yog li txhawb qhov pib thiab txij nkawm ntawm kev pw tsaug zog qeeb. Nws cov teebmeem tiv thaiv ntawm cov hlwb neuronal, tswj lawv cov qauv ib txwm muaj thiab ua haujlwm, kuj tseem ua rau tsim kom muaj ib puag ncig neural uas tsim nyog rau kev pw tsaug zog qeeb.
3. Txhim kho tus cwj pwm pw tsaug zog
Hauv kev sim coj tus cwj pwm, xws li kev sim qhib teb, nce ntxiv ntxiv rau qhov kev sim tshawb nrhiav, thiab kev ntsuas tus Tsov tus tw, DSIP peptides pom tau tias muaj kev txhim kho tseem ceeb hauv kev coj cwj pwm ntawm cov tsiaj insomniac. Hauv kev sim qhib, cov qauv pab pawg nas pom tau tias txo qis kev txav mus los thiab lub sijhawm ua haujlwm, thaum cov nas kho nrog DSIP peptide (piv txwv li, pawg P-DSIP) tau nthuav tawm ntau qhov kev txav mus los thiab lub sijhawm ua haujlwm, qhia tias DSIP peptide tuaj yeem txhim kho lub peev xwm ntawm insomniac nas thiab txo qis kev ua haujlwm inhibition los ntawm insomnia. Nyob rau hauv qhov kev ntsuam xyuas ntxiv ntxiv, cov naj npawb ntawm lub sij hawm cov qauv pab pawg nas nkag mus rau hauv qhib caj npab thiab lub sij hawm siv rau hauv qhib caj npab tau txo qis. Txawm li cas los xij, tom qab kev tswj hwm ntawm DSIP peptide, xws li hauv pawg P-DSIP, tus naj npawb ntawm lub sij hawm cov nas nkag mus rau hauv qhov qhib caj npab thiab lub sij hawm siv rau hauv qhov qhib caj npab tau nce ntxiv, qhia tias DSIP peptide tuaj yeem txhim kho kev ntxhov siab zoo li kev coj cwj pwm hauv cov nas insomniac. Nyob rau hauv qhov kev ntsuam xyuas tus Tsov tus tw, cov qauv pab pawg nas pom tias muaj kev nce ntxiv hauv lub sijhawm tsis muaj zog thiab txo qis hauv lub sijhawm tawm tsam. Txawm li cas los xij, tom qab kev tswj hwm ntawm DSIP peptide (xws li pab pawg GABA, P-DSIP pawg, thiab DSIP pawg), cov nas pom qhov txo qis hauv lub sijhawm tsis muaj zog thiab muaj kev nce ntxiv hauv lub sijhawm tawm tsam, qhia tias DSIP peptide tuaj yeem txhim kho kev nyuaj siab zoo li tus nas insomniac. DSIP peptide tuaj yeem txhim kho kev xav thiab kev coj tus cwj pwm teeb meem tshwm sim los ntawm insomnia.
Daim ntawv thov ntawm DSIP Peptide hauv Kev Tswj Pw Tsaug Zog
Hauv kev tshawb fawb soj ntsuam, hauv qee qhov kev soj ntsuam me me, tom qab tswj hwm DSIP peptide-txog cov qauv rau cov neeg mob insomnia, kev pw tsaug zog zoo ntawm qee cov neeg mob tau txhim kho mus rau qhov sib txawv, xws li lub sijhawm pw tsaug zog luv dua, nce pw tsaug zog qhov tob, thiab txo qis thaum hmo ntuj awakenings. Tsis tas li ntawd, DSIP peptide tuaj yeem siv ib leeg rau kev kho mob pw tsaug zog lossis ua ke nrog lwm cov tshuaj pw tsaug zog. Kev tshawb fawb qhia tias thaum ua ke nrog qee yam tshuaj anxiolytic lossis antidepressant, DSIP peptides pom muaj kev sib koom ua ke, txhim kho cov neeg mob pw tsaug zog zoo thiab lub siab lub ntsws. Thaum siv nrog benzodiazepines, DSIP peptides tuaj yeem txo cov tshuaj benzodiazepines, txo qhov kev pheej hmoo ntawm kev phiv tshuaj, thiab txhim kho kev kho mob.
Xaus
Raws li kev tswj hwm kev pw tsaug zog ntuj, DSIP peptide qhia tau hais tias muaj txiaj ntsig hauv kev tswj kev pw tsaug zog, kev pw tsaug zog txhim kho, thiab kev siv cov yam ntxwv.
Qhov chaw
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Cov khoom muaj rau kev tshawb fawb siv nkaus xwb:
