Twese tuzi ko guhangayika igihe kirekire bishobora gutera ibibazo byinshi byubuzima bwumubiri nubwenge, nko guhangayika, kwiheba nandi marangamutima mabi, hamwe no kubura ubushake bwo kurya, kurwara ibiro nibindi bibazo bya metabolike. Abantu benshi bahangayitse, bazerekana kurya amarangamutima (kurya amarangamutima), ni ukuvuga kurya cyane kugirango bagabanye amarangamutima mabi aterwa no guhangayika. Kurya amarangamutima akenshi biherekezwa na karori nyinshi, nikimwe mubitera umubyibuho ukabije. None, ni ubuhe buryo bukoreshwa mu guhangayika bitera ikibazo cyo kurya? Ni irihe sano riri hagati ya metabolism ya tryptophan no kurya amarangamutima? Kugira ngo ibyo bibazo bikemuke, abashakashatsi bakoze ubushakashatsi burambuye.

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Tryptophan nimwe mubintu byingenzi bya aside amine mumubiri wumuntu kandi bibanziriza neurotransmitter 5-hydroxytryptophan (5-HT, izwi kandi nka serotonine) mubwonko. Umubare munini wubushakashatsi bwerekanye ko indwara ya tryptophan metabolism ihura cyane nindwara zitandukanye zo mumutwe, nko kwiheba, guhangayika, sikizofreniya nibindi. Muri icyo gihe, tryptophan na metabolite yayo 5-HT nayo igira uruhare mu kugenzura ubushake bwo kurya no kuringaniza ingufu. Noneho, mubihe bidakira, imitekerereze ya tryptophan ihinduka? Ese iyi mpinduka ifitanye isano nimyitwarire idasanzwe yo kurya? Hamwe nibi bibazo, abashakashatsi bakoze urukurikirane rwubushakashatsi burambuye.

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Ubwa mbere, abashakashatsi bifashishije imbeba kugirango batezimbere uburyo bwo kurya bwamarangamutima (CMS). Bakoresheje imbeba imihangayiko itandukanye yoroheje idateganijwe, nko guhagarika umutima, kunyeganyega, no koga amazi akonje, muminsi 21 ikurikiranye kugirango bigane imihangayiko ikomeje, itandukanye mubuzima busanzwe. Ibisubizo byerekanye ko nyuma yiminsi 21 yumubabaro udashira, imbeba zagaragaje guhangayika cyane nimyitwarire isa nihungabana. Mu bushakashatsi bwakorewe mu murima (OFT), igihe imbeba zo mu matsinda ya CMS zagumye mu gice cyo hagati cy’umurima wafunguye zagabanutse cyane, byerekana ko impungenge zabo zariyongereye. Mu igeragezwa ryo kumanika umurizo (TST), igihe cyo guhangana nimbeba mu itsinda rya CMS cyaragabanutse cyane, byerekana ko twongerewe ibyiringiro. Muri icyo gihe, ibiryo by’imbeba mu itsinda rya CMS byiyongereye ku buryo bugaragara, ariko ibiro byagabanutse ku buryo bugaragara, byerekana ko ubushake bwabo na metabolisme byahungabanye.

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Nyuma, abashakashatsi bakoze isesengura ryibanze rya metabolomic yinzira ya tryptophan metabolike inzira ya serumu yimbeba. Ibisubizo byerekanye ko serumu tryptophan yibiri mu mbeba zo mu matsinda ya CMS yagabanutse ku buryo bugaragara, mu gihe metabolite yo hepfo 5-hydroxytryptamine (5-HT) n'ibirimo kynurenine yariyongereye ku buryo bugaragara. Isesengura ryakozwe ryerekanye ko imvugo ya mRNA ya tph1, enzyme yingenzi muri synthesis ya 5-hydroxytryptamine, yagenzuwe cyane mubice byimitsi yimbeba mumatsinda ya CMS, kandi ibikubiye muri 5-HT muri colon nabyo byagaragaje inzira yo kumanuka. Ibi byerekana ko imihangayiko idakira ihungabanya homeostasis yinzira ya tryptophane-5-HT ya metabolike yinzira yo mu mara yimbeba, bikavamo ubusumbane bwurwego rwa 5-HT.

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Nubwo tryptophan idashobora kurenga imbogamizi yubwonko bwamaraso, metabolite yayo 5-HT igira uruhare runini nka neurotransmitter muri sisitemu yo hagati yo hagati kandi igira uruhare mukugenzura imikorere myinshi yumubiri nkimyumvire, kumenya no kurya. Abashakashatsi bakomeje gusesengura impinduka mu mvugo ya neuropeptide nyinshi hamwe na 5-HT yakira uruhare mu kugaburira ubushake bwo kurya muri hypothalamus. Ibisubizo byagaragaje ko imihangayiko idakira yagenzuye cyane imvugo ya apetitepromoting neuropeptides nka AgRP na OX1R, mugihe yagabanije imvugo yibintu byangiza nka LEPR, MC4R na 5-HT1B. Ibi birerekana ko ihungabana ryinzira ya tryptophane-5-HT ishobora kuganisha ku myitwarire idasanzwe yo kugaburira bigira ingaruka kuri hypothalamic neural circuit.

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Noneho, kuzuza hamwe na tryptophan birashobora kugabanya umutima uterwa no guhangayika no kurya imyitwarire idasanzwe? Ingano ebyiri za tryptophan (100mg / kg na 300mg / kg) zahawe imbeba za CMS na gavage ya buri munsi muminsi 21. Ibisubizo byerekanye ko nyuma yiminsi 21 yo gutabarwa hamwe nigipimo kinini cya tripitofani (300mg / kg), guhangayika no kwiheba nk’imbeba mu bushakashatsi bwakorewe mu murima hamwe n’ubushakashatsi bwo guhagarika umurizo byateye imbere ku buryo bugaragara, kandi kongera ibiryo bidasanzwe no gufata ibiro byakosowe. Ubundi bushakashatsi bwerekanye ko interineti ikabije ya tryptophan ishobora kubuza kugenga ibyifuzo byo kurya cyane nka AgRP na OX1R muri hypothalamus iterwa no guhangayika karande, mugihe ugarura imvugo yibuza kurya nka LEPR, MC4R, 5-HT1B na 5-HT2C. Twabibutsa ko nubwo igipimo gito cya tryptophan (100mg / kg) kitagaragaje iterambere ryinshi mubipimo byimyitwarire, habaye impinduka zimpinduka ziterwa na hypothalamic appetit zijyanye na gene imvugo ya molekile.

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Ubundi bushakashatsi bwakozwe na molekile bwerekanye ko 5-HT, muguhuza reseptor 5-HT1B na 5-HT2C kuri hypothalamic POMC, AgRP nizindi neuron, ikabuza neurone ya AgRP / NPY itera ubushake bwo kurya, ikora neurone ya POMC ibuza ubushake bwo kurya no guteza imbere ingufu, hanyuma ikagira uruhare mukugenzura ubushake nuburemere. Ibi bitanga uburyo bukomeye bwa molekuline yo gushyigikira kunoza ibiryo byamarangamutima ukoresheje inzira ya tryptophan-5-HT.

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Abashakashatsi bifashishije kandi imbeba hypothalamic neuron selile umurongo GT1-7 kugirango barusheho kugenzura ingaruka zigenga 5-HT kuri appetit zijyanye na neuropeptides. Bavuzaga selile GT1-7 hamwe na 10μM ya corticosterone (CORT) amasaha 24 kugirango bigane ibihe bidakira. Ibisubizo byerekanye ko imvugo yo kurya itera genes nka AgRP na OX1R yagenzuwe cyane nubuvuzi bwa CORT, mugihe imvugo yo kurya ihagarika ingirabuzimafatizo nka MC4R, 5-HT1B na 5-HT2C yagenzuwe nabi. Nyuma yo kwitegura hamwe na 0.1μM 5-HT mumasaha 2, imvugo idasanzwe ya CORt iterwa na AgRP nizindi genes zishobora guhinduka cyane, kandi imvugo ya MC4R, 5-HT1B na 5-HT2C irashobora kugarurwa. Ibi byashimangiye kandi ingaruka zitaziguye za 5-HT kuri hypothalamic neuron.

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Incamake yamakuru:

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Ingaruka zo guhangayika karande kuri tryptophan metabolism homeostasis yimbeba: Guhangayika karande byatumye serumu tryptophan igabanuka (P

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Ingaruka za tripitofani ku byifuzo byo kurya no kwiheba biterwa no guhangayika karande: Kwiyongera cyane kwa tripitofani byagaruye imyitwarire idasanzwe yo kurya no gutakaza ibiro biterwa no guhangayika karande (P

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Ingaruka zo kongeramo tryptophan kuri hypothalamic igaburira neuron hamwe nubushakashatsi bwinshyi mu mbeba zidakira: Immunohistochemic irangi yerekanaga ko imvugo ya c-fos na AgRP mukarere ka ARC ka hypothalamus mumatsinda yibibazo byigihe kirekire yariyongereye cyane, mugihe imvugo ya LEPR yagabanutse cyane (P

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Ingaruka za tryptophan kumuhanda wa 5-HT metabolike muri hypothalamus yimbeba zidakira: Serum tryptophan na 5-HT byiyongereye cyane nyuma yo kongerwaho na tripitofani (P

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Muri rusange, ubu bushakashatsi bugaragaza ko imihangayiko idakira itera ihungabana rya hypothalamic apetite igenga imiyoboro ihagarika inzira ya metabolike ya tryptophane-5-HT, ari nako itera kurya amarangamutima. Kwiyongera kwa tryptophan ya exogenous, cyane cyane muri dosiye nyinshi (300mg / kg), igarura urwego 5-HT rwagati, ikora hypothalamic 5-HT1B na 5-HT2C, ikabuza neuron ya AgRP / NPY, ikora neurone ya POMC, kandi igateza ibibazo biterwa no guhangayika hamwe n imyitwarire idasanzwe yo kurya.

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Ibisubizo byubushakashatsi bifite akamaro gakomeye. Muri iki gihe cyihuta cyane, ubuzima bukabije, abantu benshi bahura nibibazo biterwa namarangamutima nibibazo byuburemere. Ubushakashatsi bwerekanye ko guhangayika igihe kirekire bituma urwego rwa tryptophan rwumubiri rugabanuka, synthesis ya 5-hydroxytryptamine igabanuka, hanyuma bigatera urukurikirane rwindwara ya neuroendocrine, biganisha ku kwiheba, guhangayika nandi marangamutima mabi, kimwe na hyperappetite, umubyibuho ukabije nibindi bibazo bya metabolike. Ubu bushakashatsi bugaragaza uruhare nyamukuru rwa tryptophan na metabolite yayo 5-hydroxytryptophan mu guhagarika umutima-amarangamutima-ibyifuzo byo gutanga umurongo, bitanga ibitekerezo nuburyo bushya bwo kugabanya imihangayiko no kunoza imitekerereze mibi hamwe nuburwayi.

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Hashingiwe ku byavuye mu bushakashatsi, abashakashatsi batanga inama z’imirire zifasha abantu guhangana n’imihangayiko. Mbere ya byose, inyongera ikwiye y'ibiribwa bikungahaye kuri tripitofani mu ndyo ya buri munsi, nk'amagi, foromaje, imbuto, ibitoki, oati, n'ibindi, birashobora gufasha kuzamura urwego rwa tripitofani mu mubiri, bigateza imbere synthesis ya 5-hydroxytryptophan, bityo bikazamura imiterere y'amarangamutima kandi bikabuza kurya stress. Ariko, twakagombye kumenya ko tryptophan mubiryo idakoreshwa 100% kandi ikoreshwa. Muri icyo gihe, igihe kinini cyongeweho urugero rwa tripitofani (nka 500mg / kg zirenga) zishobora kwangiza impyiko. Kubwibyo, muburinganire bwimirire ya buri munsi, inyongeramusaruro ya tryptophan irashobora kuba, ntugashyigikire gukoresha cyane inyongeramusaruro.

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Byongeye kandi, imyitozo iringaniye nko kwiruka, koga, yoga, nibindi, birashobora kandi gufasha kongera urwego rwa synthesis ya tryptophan na serotonine mumubiri, kugabanya imihangayiko no kunoza umwuka. Gusinzira bihagije, gutsimbataza inyifato nziza kandi yizigira, no kwiga kwerekana amarangamutima mu buryo bushyize mu gaciro ni inzira nziza zo guhangana n'imihangayiko. Iyo uhuye nibibazo bikomeye byamarangamutima nko kwiheba no guhangayika, ni ngombwa gushaka ubuvuzi bwumwuga mugihe.

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Mu gusoza, ubu bushakashatsi bugaragaza uburyo bwo kurya amarangamutima buterwa no guhangayika karande duhereye kuri metabolism ya tryptophan, kandi butanga icyerekezo gishya cyo kugabanya imihangayiko, kunoza imitekerereze idahwitse nuburwayi. Nubwo hakenewe ubundi bushakashatsi bwabaturage kugirango hongerwe urugero nigihe cyinyongera cya tripitofani mumirire, ibyavuye muri ubu bushakashatsi byaduhaye ibitekerezo bishya byo guteza imbere ubuzima bwumubiri nubwenge binyuze mumabwiriza agenga imirire. Twizera ko binyuze mu ndyo yuzuye, imyitozo ngororamubiri, gusinzira neza no guhangana n'amarangamutima meza, dushobora kurushaho gutuza duhura n'ibibazo by'ubuzima kandi tukemera ejo hazaza heza.