Research Ubushakashatsi bwa Dermorphine
Ni ubuhe bushakashatsi bwakozwe na Dermorphine?
Ubushakashatsi bwibintu bikomoka ku binyabuzima: Kuva mu myaka ya za 70, abahanga bitangiye gushakisha ibintu bifite ibikorwa byihariye bya fiyologiki biva mu binyabuzima. Abantu bamenye buhoro buhoro ko mugihe kirekire cyubwihindurize, inyamaswa zizabyara ibinyabuzima bitandukanye bidasanzwe kugirango bihuze nibidukikije kandi bikomeze ibikorwa byubuzima, kandi izo molekile zishobora kugira indangagaciro zubuvuzi.
Umwihariko wuruhu rwa Amphibian: Uruhu rw amphibian rufite imirimo myinshi, nko guhumeka, kurinda, no gusohora. Imvubura zuruhu za amphibian zirashobora gusohora ibintu byinshi bioaktique, bigira uruhare runini mukurinda abanzi karemano no guhuza ibidukikije. Ururenda rwuruhu rwinshi rwa amphibian rurimo ibintu bya peptide bikungahaye, bifite imiterere itandukanye nibikorwa bitandukanye byibinyabuzima, bikurura abahanga benshi.
Ivumburwa rya Dermorphine: Mu 1981, abahanga bo mu Butaliyani batandukanije bwa mbere Dermorphine mu ruhu rw’ibikeri by’ibiti byo muri Amerika yepfo (Phyllomedusa sauvagii). Binyuze mu isesengura ryibigize ururenda rwuruhu rwibikeri no kumenya ibikorwa byibinyabuzima, byagaragaye ko Dermorphine yarimo yagize ingaruka zikomeye zo gusesengura no gukundana cyane na reseptor ya opioid. Ubu buvumbuzi bwafunguye icyerekezo gishya cyubushakashatsi mubijyanye no kuvura ububabare.
Ni ubuhe buryo bwo gukora bwa Dermorphine?
1. Guhambira Abakira Opioid
Dermorphine ni opioide ikomeye isa na peptide ishobora guhitamo guhuza reseptor ya μ-opioid. Uku guhambira gukora reseptors, bikavamo urukurikirane rwingaruka zumubiri [1, 2] . Kurugero, mubushakashatsi bwinyamaswa, bwerekanye ingaruka zikomeye zo gusesengura [1, 2] . Ingaruka zayo zo gusesengura zishobora kugerwaho muguhagarika kwanduza ibimenyetso byububabare. Iyo ibimenyetso byububabare byandujwe muri neuron, bizatera umunezero no kurasa kwa neuron. Dermorphine imaze guhuza reseptor ya μ-opioide, irashobora kubuza kwishima kwa neuron, bityo bikagabanya kwanduza ibimenyetso byububabare.
2. Ingaruka kuri Sisitemu Nervous
Ingaruka kurwego rwumugongo
Mu bushakashatsi bwakozwe n'abantu, byagaragaye ko kwinjiza dermorphine mu mitsi bishobora gutera kwiyongera gukomeye kandi guhoraho mu ntera ya nociceptive flexor reflex yinjira mu bakorerabushake bafite ubuzima bwiza [2] . Ibi byerekana ko dermorphine ishobora kubuza kwanduza ibimenyetso bya nociceptive kurwego rwumugongo. Izi ngaruka zigaragara no mubintu bifite ibikomere byuzuye byuruti rwumugongo, bikomeza kwemeza ko dermorphine igira uruhare runini mukurinda kwanduza nociceptive kurwego rwumugongo.
Naloxone irashobora guhindura igice (hafi 50%) ingaruka zo guhagarika dermorphine kuri nociceptive spinal reflex. Ibi birashobora gusobanura ko dermorphine ikorana nabantu batandukanye ba reseptor ya opioid reseptor kugirango itange ingaruka zidasanzwe ..
Ingaruka kuri sisitemu yo hagati
Imiyoborere idasanzwe ya DM itanga ibikorwa birebire birwanya imiti igabanya ubukana [1] . Ibi byerekana ko dermorphine ishobora gukora analgesic ikora kuri sisitemu yo hagati. Nyamara, uburyo bwihariye bwibikorwa bya dermorphine muri sisitemu yo hagati yo hagati ntibirasobanuka neza.
Mu bushakashatsi bwakozwe ninkwavu, nyuma yo gutera inshinge dermorphine, imyitwarire yinkwavu yerekanaga ubwiyongere bugaragara mugihe cyo guceceka no kutimuka, no kugabanuka mubikorwa byubushake, ariko ntibyagize ingaruka kumiterere ninshuro za electroencephalogramu ya hippocampal [3] . Ibi byerekana ko dermorphine ishobora kugira ingaruka kumyitwarire imwe n'imwe ya sisitemu y'imitsi.
3. Ingaruka ku Gice cya Gastrointestinal
Dermorphine igira ingaruka ku mara yo mu nda. Ugereranije na morphine, inshinge za intracerebroventricular ziterwa na dermorphine zibuza umuvuduko w'amara nka morfine, kandi ibikorwa byayo bikubye inshuro 143 ibya morfine [4] . Ingaruka ya antagonistique ya naloxone kuri dermorphine ntabwo ikora neza kuruta iyo kuri morphine. Ubuyobozi bwa intracerebroventricular ya naloxone ya quaternised irashobora kurwanya ingaruka za dermorphine intracerebroventricular dermorphine kumara, mugihe inshinge za intraperitoneal zifite akamaro gusa mukigereranyo cya 8mg / kg. Dermorphine yatanzwe mu buryo butemewe ntigikora rwose ku kigero kinini (microgramu 0.56 kuri imbeba). Kongera igipimo cyo guterwa intraperitoneal ya dermorphine (kuva kuri microgramu 12 kugeza 6400 kuri kilo) bigira ingaruka mbi kubitera amara bidashingiye kumupanga, ariko ntibigera birenga 50%. Gusa urugero rwinshi rwa naloxone (30mg / kg, inshinge za intraperitoneal) zirashobora kurwanya ingaruka zatewe no guterwa intraperitoneal. Ibi byerekana ko ingaruka za dermorphine ku mara zishobora kuba zirimo ibice byo hagati ndetse na periferiya.
4. Ingaruka ku mitsi
Igikorwa cya Dermorphine cyakorewe ku gice cyambukiranya imitsi y igikeri nigikonoshwa [5] . Ibisubizo byubushakashatsi byerekana ko dermorphine (10 (-5) -10 (-8) M) ishobora guhagarika ibikorwa bya acetyloline, ibikorwa byizana, no kwikuramo imitsi biterwa no gukurura amashanyarazi. Izi ngaruka zose ziragoye guhinduka. Niba dermorphine yatewe mumashanyarazi mugihe cya K (+) depolarisiyasi (KCl - 100mM) yimitsi, ntishobora guhagarika ibikorwa byizana kandi biterwa. Kubwibyo, dermorphine igira ingaruka ziterwa na voltage kandi irashobora gukora kumuyoboro wa Ca (2+) uva mumitsi ya selile.
5. Isano iri hagati yimiterere ya molekulari nuburyo bukoreshwa
Ibikoresho bya molekuline bigereranywa byakozwe kuri dermorphine (Pattabiraman N, 1986). Ubushakashatsi bwerekana ko D-Ala2 kuri N-terminus hamwe n’ibisigisigi bya L-Pro6 kuri C-terminus mu ruhererekane rwa dermorphine byerekana ko hashobora kubaho β-guhinduka. Urebye kuri stereochemiki, hashobora kubaho ubwoko butatu (II ', III', na V ') bwa β-guhinduka kuri N-terminus ya peptide, nubwoko bubiri (I na III) bwa β-guhinduka kuri C-terminus. Mu mibare ya molekulike yo kubara, itandatu ihujwe hamwe nimwe yagutse yahinduwe kugirango isuzume isano iri hagati ya dermorphine. Muri byo, ibice bitatu byahujwe bifite ingufu nke kandi bifite ibimenyetso rusange bikurikira: ingufu zisa, imigozi itatu ya hydrogène, igice kimwe cya kabiri β-urupapuro, hamwe n’imikoranire myiza ya Tyr1-Tyr5. Kubaho β -urupapuro rwimiterere birashobora kugira uruhare mubikorwa byo guhitamo hagati ya dermorphine na μ-reseptor.
Ni ubuhe buryo bukoreshwa na Dermorphine?
Yifashishijwe mu gucunga ububabare bwa nyuma yo kubagwa: Ubushakashatsi bwateganijwe, bugenzurwa na platbo mu 1985 bwerekanye ko Dermorphine yatanzwe binyuze mu nzira ya intrathecal yakoraga neza cyane kuruta umwanya wa platbo hamwe na morphine ikoreshwa mu gucunga ububabare nyuma yo kubagwa [6, 7] . Ibi byerekana ko Dermorphine ishobora kuba ifite imbaraga nyinshi zo kugabanya ububabare nyuma yo kubagwa. Ku barwayi nyuma yo kubagwa, gucunga neza ububabare ntibishobora guteza imbere ihumure ry’abarwayi gusa ahubwo binafasha abarwayi gukira no gusubira mu buzima busanzwe.
Gusaba ubuvuzi bwa Palliative: Urebye ingaruka nziza zidasanzwe zo kuvura, Dermorphine yanasabwe gukoreshwa mu kuvura indwara zanduza abarwayi bateye imbere [6, 7] . Mu buvuzi bwa palliative, kugabanya ububabare bw’abarwayi nintego yingenzi, kandi Dermorphine, hamwe ningaruka zayo zikomeye zo kuvura no kugabanya ingaruka mbi, itanga uburyo bushoboka bwo kugabanya ububabare bw’abarwayi bateye imbere.
Ingaruka zibuza ububabare bw'umugongo: Ubushakashatsi bwerekanye ko Dermorphine ishobora kubuza kwanduza nociception mu ruti rw'umugongo. Mu bakorerabushake bafite ubuzima bwiza, kwinjiza imitsi ya 0.16mg / kg ya Dermorphine birashobora kandi ku buryo budasubirwaho kongera urwego rwa nociceptive flexor reflex [8] . Ingaruka nkizo zagaragaye no mubintu bifite ibikomere byuzuye byumugongo, byerekana ko Dermorphine ikora cyane kurwego rwumugongo kugirango ibuze kwanduza ububabare. Izi ngaruka zo kubabaza umugongo zitanga ibyiringiro bishya byo kuvura abarwayi barwaye indwara zifata uruti rwumugongo.
Mu gusoza, Dermorphine ni peptide ikomeye ya opioide ishobora guhuza na reseptor ya μ-opioid, ikerekana ingaruka zikomeye zo kubabaza no kubuza kwanduza ibimenyetso bya nociceptive mu ruti rw'umugongo. Ifite uburyo bushoboka muburyo bwo kubabara nyuma yubuvuzi, kuvura palliative, nibindi, kuzana ibitekerezo bishya byo kuvura ububabare.
Ibyerekeye Umwanditsi
Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.
Umwanditsi w'ikinyamakuru
Giuliano Fontani ni umushakashatsi ufitanye isano na kaminuza ya Siena, mu Butaliyani, yibanda kuri neurosciences na physiologiya. Yize ku ngaruka za dermorphine, peptide isanzwe ibaho, ku myitwarire ndetse n’ibikorwa by’amashanyarazi ya hippocampal mu nkwavu, agira uruhare mu gusobanukirwa imikorere ya reseptor ya opioid. Igikorwa cye kandi kigaragaza isano iri hagati yibikorwa byubwonko nimyitwarire, hamwe nibisohoka mubinyamakuru nka Life Science. Giuliano Fontani yanditse ku rutonde rw'ibisobanuro [3].
