UNat Med. Umbhalo-ngqangi wombhali; ifumaneka kwi-PMC 2011 Mar 16.
Ishicilelwe kwifomu yokugqibela ehleliweyo njenge:
PMCID: PMC3058782
I-NIHMSID: I-NIHMS277755
Uthixo wamaRoma uJanus unobuso obubini, obunye bujonge ngasemva nobunye kubomi obungaphambili. NjengoJanus, sinokujonga emva kule minyaka imbalwa idlulileyo kwaye siyayixabisa into esiyifundileyo malunga neendima ze-orexin neuropeptides kulawulo lokuphaphama nokulala, ulawulo lobunzima bomzimba kunye nemetabolism, kunye nolawulo lwenkuthazo kunye nokulutha.1. Ukujonga phambili, sinokubona kungekudala ukusetyenziswa kwezi zinto zifunyenweyo kuqeqesho lwezonyango.
Kulo mbandela, iBrisbare-Roch okqhubekayo. chaza inoveli, ichiza elilawulwa ngomlomo elivelisa ukozela ngokuthintela okukhethiweyo kokubonakaliswa kwe-orexin2. Ngokunokwenzeka, eli chiza linokuba luncedo eklinikhi ekukhuthazeni ukulala, kwaye, ngokumodareyitha iisekethe zomvuzo, linokuba lunyango olunoveli lokukhotyokiswa ziziyobisi.
I-Orexin-A kunye ne-orexin-B (ekwabizwa ngokuba yi-hypocretin-1 kunye ne-hypocretin-2) ziveliswa liqela lee-neurons kwi-posterior lateral hypothalamus (Ikhiwane. 1). I-orexin neurons inceda ukukhuthaza kunye nokugcina ukuphaphama ngokubonelela nge-excitatory drive kwiindawo ezahlukeneyo zengqondo ezilawula ukuvuswa kunye nokuphaphama. Ukongeza, ii-orexins ziyimfuneko yokulawula ukulala kwe-REM, inqanaba lokulala eliphawulwa ngamaphupha acacileyo kunye nokukhubazeka phantse zonke izihlunu.
Ukubaluleka kwe-orexin kucace ngakumbi kubantu abane-narcolepsy. Aba bantu banelahleko efunyenweyo yee-neurons ezivelisa i-orexin, nto leyo ekhokelela kubuthongo obungapheliyo kunye nokungenelela ekuvukeni kokulala kwe-REM-ezifana neziganeko, kubandakanya nokubona okufana nephupha kunye ne-cataplexy (iziqephu ezibangelwa ngokweemvakalelo zobuthathaka bemisipha obufana nokukhubazeka kokulala kwe-REM.3-5).
IBrisbare-Roch okqhubekayo. ufumanise ukuba umchasi omtsha we-orexin (ACT-078573) uvale ngokukhetha zombini i-orexin receptors (OX).1 kunye ne-OX2) kugxininiso lwe-nanomolar, kodwa yayinobudlelwane obuncinane kwezinye ii-G protein-coupled receptors2. Ichiza lalisebenza ngomlomo kwaye langena ngokukhawuleza ebuchotsheni. Xa kunikwa iigundane ngexesha labo elisebenzayo, kwandisa ukulala kwe-REM kunye ne-non-REM ubuncinane ubuncinane kwiiyure ze-12, kwaye izinja eziphathwa ngayo zichitha ixesha elingakumbi kwindawo yokulala njengoko kuboniswe ngohlalutyo lwevidiyo. Kwinani elincinci labantu abaphathwa ngeziyobisi emini, abaninzi babeziva belele, kwaye, xa bevunyelwe ukuba balale, balala ngokukhawuleza. Uninzi lwee-sedatives lunokuvelisa iimvakalelo zokunxila okanye ukungazinzi, kodwa ezi kunye nezinye iziphumo ebezingalindelekanga zazingaqhelekanga kulo mchasi we-orexin.
Ubuthongo obuveliswa leli chiza kuqinisekisa ukuba ii-orexins zikhuthaza ukuphaphama ebantwini, njengoko kucetyisiwe luphando oluninzi lwezilwanyana. Okubaluleke ngakumbi, eli chiza linokuba nezicelo ezininzi zeklinikhi eziluncedo.
Xa uthi krwaqu nje umntu usenokucinga ukuba umchasi we-orexin unokuba luncedo kukhetho lwangoku lwamachiza okuphuthelwa. Uninzi lwamayeza ngoku asetyenziselwa ukukhuthaza ubuthongo, njenge-benzodiazepines kunye nee-agent ezintsha ezifana ne-zolpidem, ukwandisa ukubonakaliswa nge-GABA.A abamkeli. Olunye ukhetho lubandakanya iGABAB ii-agonists, i-antihistamines kunye ne-melatonin agonists, kodwa izigulane ngamanye amaxesha zifumana amayeza akhoyo ngoku angasebenziyo okanye iziphumo ebezingalindelekanga azinyamezeleki.
Iziphumo zakwangoko ngalo mchasi we-orexin zibonisa ukuba inokukhuthaza ukulala, kodwa ayinguye wonke umntu onengxaki yokulala onokuthi ayifumane iyasebenza. Ababhali babonisa ukuba le khompawundi yayisebenza ngokumodareyitha ekukhuthazeni ukulala xa inikwe iimpuku kunye nezinja ngexesha elisebenzayo, kodwa, ngokungafaniyo ngokumangalisayo nezithomalalisi zendabuko, ayizange ibe nempembelelo xa inikwe ngexesha labo lokuphumla. IiOrexins zikhutshwa ngexesha lokuvuka okusebenzayo kodwa hayi ngexesha lokulala6-8, ngoko eli chiza alinakunceda abantu abaninzi abanengxaki yokuphuthelwa. Kwelinye icala, inokusebenza kakhulu kubasebenzi beshifti okanye abantu abane-jet lag bezama ukulala xa iwotshi yabo yebhayoloji ibonakalisa ukuphaphama.
Kwiimpuku, iimpuku, izinja kunye nabantu, ukuphazamiseka kokubonakaliswa kwe-orexin kubangela i-narcolepsy nge-cataplexy.3-5,9-11. Nangona umchasi omtsha we-orexin evimba ngokupheleleyo umqondiso we-orexin kwaye uvelise ukozela, ngokumangalisayo akubonakali ngathi kuvelisa i-cataplexy. Ngokuyinxenye, oku kunokuba sisiphumo senkcazo yababhali ye-cataplexy eyahlukileyo kwizifundo zangaphambili kwiintonga ze-narcoleptic (apho ipateni ye-EEG ngexesha le-cataplexy ifana naleyo ibonwa kubuthongo be-REM; bona iirefs. 10,12). Kodwa nangona eli chiza lanikwa abantu, akukho cataplexy ecacileyo eyenzekayo.
Oku kunqongophala kwe-cataplexy kusenokuba ngenxa yeemeko zovavanyo: i-cataplexy ebantwini isoloko ibangelwa kukuhleka, kwaye ulonwabo olusuka entliziyweni kunzima kakhulu ukulufumana elebhu. Kwakhona kunokwenzeka ukuba i-cataplexy ikhula kuphela ngelahleko engapheliyo yokubonakaliswa kwe-orexin, ngoko kuya kubaluleka ukuvavanya ngokucophelela ukuba i-cataplexy ikhula emva kweeveki zonyango kunye nomchasi.
Olunye usetyenziso olunokwenzeka lwalo mchasi we-orexin lucetyiswa ngumsebenzi omtsha obonisa ukuba i-orexin neurons idlala indima ebalulekileyo ekumodareyitheni iindlela zomvuzo.13. Izivuseleli ezivuzayo ezifana ne-cocaine, i-morphine kunye nokutya okubangela ukukhutshwa kwe-dopamine kuqikelelo lwe-mesolimbic dopamine, kunye nomsebenzi ogqithisileyo kule ndlela kunokubangela ukuba likhoboka. I-Orexins iphucula ukubonakaliswa kule nethiwekhi yomvuzo, kwaye iimpuku eziswele i-orexins azityi nje kancinci kodwa zikwabonisa isimilo esincinci sokulutha nge-morphine okanye i-amphetamines.14,15. Ke, ngokunciphisa umsebenzi kwiindlela zomvuzo, umchasi we-orexin unokuba luncedo kunyango lokutyeba kakhulu okanye ukuba likhoboka leziyobisi ngokunciphisa ukutya okanye ukunqwenela iziyobisi kunye nomngcipheko wokuphinda ubuyele. Nangona kunjalo, oku kusenokungabi lula njengoko kubonakala: iimpuku kunye nezinja eziphathwe ngumchasi we-orexin zazinobuvila kwaye zihamba kancinci malunga neekheji zazo. Akukacaci nokuba bashukume kancinane ngenxa yokuba besozela okanye ngenxa yokuba iindlela zabo zokuvuza zazingasebenzi (ukunciphisa inkuthazo yabo yokuhamba).
Ke ngoko, umchasi we-orexin unokunceda abantu abanengxaki yokusetyenziswa gwenxa kweziyobisi kuphela ukuba inokunikwa ngedosi ethomalalisa umsebenzi kwiindlela zomvuzo ngaphandle kokuvelisa i-sedation eninzi okanye ukungabikho kwenkuthazo ngokubanzi.
Ubutyebi bophando lwezilwanyana luye lwabonisa ukubaluleka kwe-orexin ekukhuthazeni ukuvuswa, ukulawula umvuzo kunye nokuqhuba ukutya, kwaye lo mchasi omtsha unika ithuba lokuqonda kakuhle imisebenzi ye-orexin ekuziphatheni komntu. Iziphumo zakwangoko ngeli chiza ziyakhuthaza, kodwa kuninzi ekufuneka kwenziwe phambi kokuba liziswe ekliniki. Okokuqala, kuya kuba yimfuneko ukuchaza ukuba zeziphi izigulana ezinokuthi zixhamle kwizenzo zokuthomalalisa eli chiza; emva koko, ukurekhodwa kokulala kuya kufuneka kuhlolwe ngokweenkcukacha ukuze kuqinisekiswe ukuba ukusetyenziswa ngokukhawuleza kunye nokungapheliyo komchasi kuvelisa ubuthongo obuhle ngaphandle kokubangela i-cataplexy xa izigulane zivukile. Kusenokuba luncedo ukuvavanya lo mchasi njengonyango lwenoveli kunyango lokusetyenziswa gwenxa kweziyobisi.
Nangona kunjalo, njengobuso obubini bukaJanus, kuya kubaluleka xa kuvavanywa abachasi be-orexin ukuba balumkele iziphumo zobunye ubuso babo: ukunciphisa inkuthazo eyona nto ibalulekileyo ebomini.
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