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.
Dermorphin yog ib qho muaj zog opioid peptide cais tawm ntawm daim tawv nqaij ntawm qee hom qav.
Lub Mechanism ntawm Dermorphin's Analgesic Effects
Kev sib tham nrog Opioid Receptors
Dermorphin feem ntau siv nws cov teebmeem analgesic los ntawm kev cuam tshuam nrog μ-opioid receptor (MOP). Lub μ-opioid receptor yog tus tswv cuab tseem ceeb ntawm tsev neeg opioid receptor thiab ua lub luag haujlwm tseem ceeb hauv kev kho mob. Dermorphin thiab nws cov analogues tshwj xeeb tuaj yeem khi rau MOP receptor, zoo ib yam li qhov tseem ceeb haum rau hauv lub xauv, yog li ua kom cov kev taw qhia hauv qab. [Cys (ATTO 488) 8] Dermorphin - NH₂ (DermATTO488), ib qho tshiab fluorescent Dermorphin analog raws li ATTO488, khi rau HEK thiab CHO hlwb qhia txog tib neeg MOP receptors thiab nthuav tawm cov yam ntxwv zoo sib xws rau Dermorphin. Nws stimulates G protein binding, txhawb GTPγ [35S] khi, yog li ua kom muaj feem cuam tshuam cov teeb liab, thiab thaum kawg inhibits qhov mob teeb liab kis tau tus mob. Dermorphin kuj tseem txhawb nqa ERK1/2 phosphorylation, ntxiv rau kev cuam tshuam rau cov txheej txheem lom neeg hauv lub cev thiab koom nrog kev tswj hwm ntawm cov teebmeem analgesic.
Inhibition ntawm mob teeb liab kis tau tus mob ntawm tus txha caj qaum theem
Cov kev tshawb fawb sim tau pom tias Dermorphin cuam tshuam qhov mob teeb liab kis ntawm tus txha caj qaum. Hauv kev sim, kev txhaj tshuaj ntawm 0.16 mg / kg Dermorphin ua rau muaj qhov tseem ceeb thiab muaj kev txhawb nqa ntawm qhov pib ntawm nociceptive flexion reflex qhov pib hauv cov neeg ua haujlwm noj qab haus huv, thiab cov txiaj ntsig no tau tshaj tawm zoo sib xws hauv cov neeg mob uas muaj kev puas tsuaj rau tus txha caj qaum, qhia tias Dermorphin feem ntau cuam tshuam qhov kev hloov pauv ntawm noci. Cov txheej txheem ntawm kev txiav txim no yuav cuam tshuam nrog Dermorphin txoj cai ntawm kev tso tawm neurotransmitter nyob rau hauv tus txha caj qaum lossis nws qhov kev txiav txim ncaj qha ntawm tus txha caj qaum neurons. Tus txha caj qaum ua haujlwm yog qhov chaw tseem ceeb rau qhov mob kis tau tus mob, thiab Dermorphin qhov kev hloov kho ntawm nws txoj haujlwm ua haujlwm tau zoo cuam tshuam qhov kev sib kis ntawm qhov mob mus rau lub hlwb, yog li ua tiav cov teebmeem analgesic.
Cov yam ntxwv tshwj xeeb receptor kev ua haujlwm
Txawm hais tias naloxone tuaj yeem cuam tshuam tag nrho cov teebmeem ntawm morphine thiab opioid analogs, nws tuaj yeem tsuas yog qee qhov (kwv yees li 50%) thim rov qab Dermorphin cov nyhuv inhibitory ntawm nociceptive spinal reflexes. Qhov no qhia tau hais tias Dermorphin cuam tshuam nrog ntau pawg ntawm spinal opioid receptors thaum inducing analgesia, thiab nws cov txheej txheem ntawm kev ua txawv ntawm cov tshuaj opioid tshuaj. Hom kev ua no muaj qee qhov zoo hauv kev siv tshuaj tua kab mob, xws li txo cov kev mob tshwm sim uas cuam tshuam nrog cov tshuaj opioid.
Analgesic Performance of Dermorphin nyob rau hauv Tsiaj Experiments
Cov nyhuv analgesia nyob rau hauv ntau yam tsiaj qauv
Hauv ntau hom tsiaj mob, Dermorphin tau pom tias muaj zog ua kom muaj zog. Hauv kev sim xws li tail-flick, kub phaj, tail pinch, formalin, thiab acetic acid writhing tests, intraperitoneal kev tswj hwm ntawm Dermorphin thiab nws cov peptides cuam tshuam txo cov tsiaj rhiab heev rau qhov mob thiab nce lawv qhov mob. Cov kev sim no simulated qhov mob ntawm ntau qib thiab hom, ua kom paub tseeb tias Dermorphin lub peev xwm analgesic. Hauv kev sim ntsuas kub, tom qab muab Dermorphin rau cov tsiaj, lub sij hawm latency rau licking lawv paws lossis dhia tau ntev heev, qhia txog qhov mob tsis muaj zog rau cov thermal stimulation, yog li qhia tau hais tias Dermorphin cov nyhuv analgesic zoo heev.
Sib piv qhov zoo dua lwm cov tshuaj analgesic
Piv nrog rau cov tshuaj analgesic ib txwm muaj xws li morphine, Dermorphin nthuav tawm cov txiaj ntsig tseem ceeb hauv qee yam. Hauv cov qauv tsiaj, tom qab kev tswj hwm intracerebroventricular, Dermorphin nthuav tawm ntau yam kev xaiv thiab muaj zog ua kom muaj zog tshaj li morphine, nrog rau lub sijhawm ntev ntawm kev ua. Qee qhov kev sib xyaw ua ke Dermorphin tetrapepetides kuj tau pom tias muaj kev ua xua rau cov tshuaj tua kab mob siab, nrog rau cov tshuaj tua kab mob muaj zog li ntawm 1,500 zaug thiab 17 npaug ntawm cov tshuaj morphine tom qab intracerebroventricular lossis subcutaneous tswj hauv cov nas, feem. Cov txiaj ntsig zoo no muaj kev cia siab rau kev siv tshuaj kho mob ntawm Dermorphin hauv kev ua kom mob plab, muaj peev xwm hais txog qhov tsis zoo ntawm cov tshuaj analgesic, xws li kev ua kom tsis muaj zog lossis lub sijhawm ntev.
Kev tshawb fawb thiab kev tshawb fawb ntawm Dermorphin hauv tib neeg
Cov txiaj ntsig kev sim thaum ntxov
Hauv xyoo 1985, qhov kev sim tshuaj ntsuam xyuas cov placebo tswj tau los ntawm kev siv Dermorphin rau qhov mob tom qab ua haujlwm tau pom tias Dermorphin tau tswj hwm los ntawm kev txhaj tshuaj intrathecal tau ua tau zoo dua cov placebo thiab morphine (siv raws li kev siv tshuaj sib xyaw) hauv cov ntsiab lus ntawm kev ua kom zoo. Txoj kev tshawb nrhiav thaj av no tau muab pov thawj tseem ceeb rau kev siv tshuaj kho mob ntawm Dermorphin hauv kev ua xua, qhia txog nws qhov peev xwm loj heev hauv kev tswj xyuas qhov mob tom qab.
Muaj peev xwm thov Scenarios
Kev Tswj Kev Mob Tom Qab: Kev phais mob tuaj yeem ua rau mob hnyav tom qab phais mob, cuam tshuam rau cov neeg mob rov zoo thiab lub neej zoo. Dermorphin tau pom tias muaj txiaj ntsig zoo hauv kev txo qhov mob tom qab phais hauv kev sim tshuaj thaum ntxov ua rau nws yog qhov kev xaiv tshiab rau kev mob ntshav qab zib analgesia. Piv nrog rau cov tshuaj kho mob tom qab phais tas, nws cov txheej txheem tshwj xeeb ntawm kev ua thiab qhov zoo-xws li txo kev pheej hmoo ntawm kev mob siab rau thiab kev vam khom-ua rau cov neeg mob muaj kev nyab xeeb dua thiab muaj txiaj ntsig zoo tshuaj tiv thaiv.
Kev kho mob ntev: Rau cov neeg mob uas mob ntev, tshwj xeeb tshaj yog cov neeg uas muaj cov lus teb tsis zoo rau cov tshuaj analgesic ib txwm muaj lossis muaj kev phiv loj heev, Dermorphin tuaj yeem ua txoj kev kho mob tseem ceeb. Hauv kev tswj cov mob ntev hauv cov neeg mob qog noj ntshav, txoj kev kho tam sim no tseem muaj qee yam kev txwv. Qhov tshwm sim ntawm Dermorphin coj kev cia siab tshiab rau cov neeg mob no. Nws cov teebmeem analgesic ntev ntev tuaj yeem tswj tau qhov mob tsis tu ncua hauv cov neeg mob qog noj ntshav thiab txhim kho lawv lub neej zoo.
Palliative care: Hauv cov chaw kho mob palliative, alleviating cov neeg mob qhov mob yog qhov tseem ceeb tshaj plaws. Dermorphin cov khoom muaj zog ua kom muaj zog ua rau nws yog ib tus neeg sib tw zoo rau kev txo qis qhov mob kawg ntawm lub neej hauv kev saib xyuas palliative. Los ntawm cov kev tswj hwm tsim nyog thiab kev hloov tshuaj, nws tuaj yeem pab cov neeg mob txo kev txom nyem thiab txhim kho kev nplij siab thaum lub sijhawm kawg ntawm lub neej.
Xaus
Raws li ib yam khoom uas muaj ib qho tshwj xeeb analgesic mechanism thiab cov teebmeem analgesic tseem ceeb, Dermorphin tuav cov ntawv cog lus hauv kev tswj qhov mob.
Qhov chaw
[1] Giakomidi D, Bird MF, McDonald J, et al. Kev ntsuam xyuas ntawm [Cys(ATTO 488)8]Dermorphin-NH2 raws li cov cuab yeej tshiab rau kev kawm ntawm μ-opioid peptide receptors[J]. Plos Ib, 2021,16(4):e250011.DOI:10.1371/journal.pone.0250011.
[2] Hesselink J, Schatman M. E. Kev tshawb pom ntawm cov tshuaj qub: cov ntaub ntawv tsis nco qab ntawm dermorphin rau kev mob tom qab phais thiab palliation [J]. Phau ntawv Journal of Pain Research, 2018,11:2991-2995.DOI:10.2147/JPR.S186082.
[3] Guzevatykh LS, Voronina TA, Emel'Ianova TG, et al. Kev sib piv ntawm cov kev ua ub no ntawm dermorphin, [DPro6]-dermorphin, thiab lawv C-terminal tripeptides [J]. Izv Akad Nauk Ser Biol, 2007(5): 577-582. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18038625&query_hl=1
[4] Sandrini G, Degli UE, Salvadori S, et al. Dermorphin inhibits spinal nociceptive flexion reflex hauv tib neeg [J]. Brain Research, 1986,371(2):364-367.DOI:10.1016/0006-8993(86)90376-8.
[5] Salvadori S, Marastoni M, Balboni G, et al. Synthesis thiab opioid kev ua ntawm dermorphin tetrapeptides bearing D-methionine S-oxide ntawm txoj hauj lwm 2 [J]. Phau ntawv Journal of Medicinal Chemistry, 1986,29(6):889-894.DOI:10.1021/jm00156a003.
Cov khoom muaj rau kev tshawb fawb siv nkaus xwb:
