Ubururu bwa metilene ku gukomereka k'ubwonko: gusobanukirwa ibimenyetso by'ubushakashatsi bwo mu nyamaswa

Gukubitwa ku mutwe, kuziba k'umutsi utwara amaraso, n'indwara yangiza buhoro buhoro ingirabuzimafatizo z'imyakura byose bishobora kurangirira ku kibazo kimwe: ubwonko ntibuba bugifite ingufu zo gukora umurimo wabwo. Iryo herezo bahuriyeho ni ryo rituma ikinyabutabire kimwe gikomeza kugaragara mu bushakashatsi kuri ibyo bintu uko ari bitatu. Ariko guhurira ku herezo ntibivuga ko ari igitekerezo kimwe. Umuti utanzwe mbere yo gukomereka, umuti utanzwe mu isaha ikurikira gukomereka, n'umuti usuzumwe hashize amezi, bigerageza ibitekerezo bitandukanye, nubwo urushinge rwaba rurimo ya mazi amwe y'ubururu.

Iyi ngingo ikurikirana igice cy'ubwo bushakashatsi kijyanye no gukomereka. Isuzuma icyo gukoresha ubururu bwa metilene ku gukomereka k'ubwonko bisobanura mu igerageza ku nyamaswa, itandukanya gukomereka bitewe n'ihungabana na sitroke ndetse no kwangirika buhoro buhoro kw'ingirabuzimafatizo z'imyakura, kandi igaragaza impamvu igihe ingano y'umuti yatangiwe gisobanura itandukaniro ryinshi hagati y'ubushakashatsi.

Uburyo butatu bwo kwangirika, ikibazo kimwe cyo kubura ingufu

Uburyo bw'imikorere buhuza izi ngero z'igerageza buri muri mitokondiriya. Ubusanzwe, elegitoroni zinyura mu ruhererekane ruzitwara kugira ngo hakorwe ATP, kandi iyo uru ruhererekane rukora neza, rugenzura ubwinshi bw'ubwoko bwa ogisijeni bugira ubukana mu mikoranire y'ibinyabutabire. Nyuma yo gukomereka, bimwe mu bice by'uru ruhererekane biradindira, umusaruro wa ATP ukagabanuka, naho ikorwa ry'uduce tw'ibinyabutabire twitwa radikali twigenga rikiyongera. Isesengura ryo muri Molecular Neurobiology ryo mu 2018 risobanura ubururu bwa metilene nk'ubundi buryo bwo gutwara elegitoroni: bwakira elegitoroni zivuye kuri NADH bukazigeza kuri sitokorome c, ibyo bikongera ibikorwa by'urusobe IV kandi bikagarura ikorwa rya ATP n'igihe igice kibanza cy'urwo ruhererekane cyangiritse.

Imibare yatangajwe irasobanutse. Mu myiteguro y'ingirabuzimafatizo n'uduce tw'inyama twakoreshejwe mu igerageza, ibikorwa by'urusobe IV byiyongereyeho 30 kugeza kuri 100 ku ijana, mu gihe ikoreshwa rya ogisijeni ryiyongereye ku kigero gihuye na byo. Ibyo byerekana ko elegitoroni z'inyongera zakoze umurimo w'ingirakamaro aho gusohoka nk'udukoko twa radikali. Mu buryo bwo kwigana sitroke mu mbeba nini, ikorwa rya ATP mu gace kangiritse ryari hejuru hafi 30 ku ijana nyuma y'amasaha 24 umuti utanzwe, ugereranyije n'inyamaswa zitawuherewe. Isesengura ryo muri Biochemistry (Moscow) ryo mu 2022 ryongeraho ingaruka zikurikiraho: igabanuka ry'ihungabana riterwa n'ubukana bwa ogisijeni, iry'ububyimbirwe mu myakura, n'iry'urupfu rw'ingirabuzimafatizo rugengwa n'imikorere yazo, hamwe n'ingaruka kuri monoamine oxidase, nitric oxide synthase, ikorwa rya mitokondiriya nshya, kwiyogereza kw'ingirabuzimafatizo, no kwikusanya kwa poroteyine zizingiye nabi.

Bityo igitekerezo kiroroshye. Gukomereka kubangamira inzira isanzwe ya elegitoroni, maze ubururu bwa metilene bugatanga indi nzira zinyuramo. Ibikurikiraho byose bireba ubwoko bw'igikomere, igihe umuti utangiwe, n'uburyo ibisubizo bipimwa.

Gukomereka bitewe n'ihungabana si sitroke

Mu buryo bwo kwigana gukomereka k'ubwonko bitewe n'ihungabana, imbaraga zikubita icyarimwe. Ukwangirika kwa mbere guterwa n'imbaraga zikubise: inyama ziracika, imitsi y'amaraso igaturika, kandi urubibi rutandukanya amaraso n'ubwonko rukava ku murongo mu minota mike. Icyo ubururu bwa metilene bushobora kugira icyo buhinduraho ni icyiciro cya kabiri gikurikiraho mu masaha no mu minsi, igihe mitokondiriya zo mu nyama zarokotse zidindira, ububyimbirwe bugakwira, n'amazi agatuma habaho kubyimba. Ibipimo by'ibisubizo muri ubwo bushakashatsi bikurikiza uko ibyo bigenda bikurikirana: ingano y'agace kangiritse, amazi ari mu bwonko, kurokoka kw'ingirabuzimafatizo z'imyakura hafi y'ahakubiswe, n'imyitwarire yo nyuma nko gusubirana ubushobozi bwo kugenda cyangwa kwiga inzira zo mu mwanya urimo inzitane.

Mu buryo bwo kwigana sitroke cyangwa ibura ry'amaraso mu bwonko bwose, ikibitera kiba giteye ukundi. Urujya n'uruza rw'amaraso rurahagarara, kubura ingufu bigakurikiraho mu minota mike, kandi kongera gutemba kw'amaraso kukazana ukwako kwangirika guterwa no kugaruka kwayo. Aha, igihe umuti utangiwe gishingira ku byabaye mu mutsi w'amaraso, akenshi mu minota mike ikurikira kuziba kwawo cyangwa kugaruka kw'amaraso. Ibipimo by'ibisubizo bigaragaza uko inyama zimeze mu masaha kugeza ku munsi umwe cyangwa ibiri: ingano y'agace kapfuye kubera kubura amaraso, urujya n'uruza rw'amaraso, n'isubirana rya mbere ry'ubushobozi bwo gukora. Bumwe mu buryo bukoreshwa mu bushakashatsi kuri sitroke ni ugutanga umuti mbere, inyamaswa zikawuhabwa mbere y'uko umutsi uzibwa. Ibyo bigerageza gukumira mu buryo nta gerageza ryo gukomeretsa umutwe ryakwigana mu bantu ryubahiriza amahame mbwirizamuco.

Ibisubizo kuri sitroke ni byo bifite ibimenyetso bikomeye kurusha ibindi mu bushakashatsi ku gukomereka, kandi birimo n'urugero rusobanutse kurusha izindi rw'aho nta nyungu yabonetse. Imbeba nini zahawe ubururu bwa metilene igihe amaraso yagarukaga nyuma y'isaha imwe umutsi wo hagati utwara amaraso mu bwonko uzibye, ku munsi wa 2 zari zifite uduce twapfuye duto ho 30 ku ijana, kandi igice kinini kurushaho cy'agace ko hagati kari mu kaga n'akaruzengurutse cyararokotse (Shen, 2013). Ubushakashatsi bwakoresheje kuziba kudakurwaho bwagaragaje ko inyama zari mu kaga zagendaga zihinduka izipfuye buhoro kurushaho, ariko nta kugabanuka kwabaye ku ngano ya nyuma y'agace kapfuye nyuma y'amasaha 24, kuri buri ngano y'umuti muri ebyiri zageragejwe (Rodriguez, 2014). Ubushakashatsi bwa gatatu ku kuziba bwagabanyije ingano y'agace kapfuye hafi kimwe cya kabiri ku ngano y'umuti yo hagati, kandi bwitegereza mu buryo butaziguye imiterere y'utuntu duto tugize mitokondiriya n'uko ingirabuzimafatizo zikuraho mitokondiriya zangiritse mu bwonko bwabuze amaraso. Bwanatangaje ikintu kitari cyitezwe: urupfu rw'ingirabuzimafatizo rugengwa n'imikorere yazo rwapimwe rwariyongereye, mu gihe urupfu rwazo rutagenzurwa rwagabanutse (Di, 2015). Naho mu ibura ry'amaraso mu bwonko bwose, guhabwa ubudahwema ingano nto y'umuti binyuze mu mutsi byagaruye ibikorwa bya sitokorome c oxidase, urugero rwa ATP, n'itandukaniro ry'umuriro w'amashanyarazi ku gihu cya mitokondiriya mu gace ka CA1 ka hipokampe gakangirika byoroshye, birinda izo ngirabuzimafatizo z'imyakura, kandi birinda ubushobozi bwo kwibuka ahantu (Lu, 2016). Icyo gipimo cya CA1 gikwiye kwitabwaho: ni amakuru apimwe mu buryo butaziguye kuri ATP no ku ruhererekane rw'imikorere yo guhumeka imbere mu bwonko bwakomeretse, ibintu ubushakashatsi kuri TBI akenshi buvuga bushingiye ku bindi bimenyetso aho kubipima.

Kwangirika buhoro buhoro kw'ingirabuzimafatizo z'imyakura bitandukanye n'ibyo byombi. Mu buryo bwo kwigana indwara za Alzheimer, Parkinson na Huntington, inyamaswa zihabwa umuti mu byumweru cyangwa amezi, hagapimwa kwikusanya kwa poroteyine, uko dopamine ikoreshwa, cyangwa igabanuka rigenda buhoro ry'ubushobozi bwo gutekereza no gusobanukirwa. Ibyo bipimo hafi nta cyo bihuriyeho n'agace kangiritse gapimwe nyuma y'iminsi mike habaye gukubitwa. Abasomyi bafata igisubizo cyo mu cyiciro kimwe bakakijyana mu kindi baba bambukije ibyabonetse urubibi amagerageza atigeze yambuka. Inyandiko yacu iyobora mu bushakashatsi ku kwangirika kw'ingirabuzimafatizo z'imyakura igumisha ubwo bushakashatsi bw'igihe kirekire mu rwego bwabwo, kandi igereranya n'ibimenyetso bireba sitroke gusa ritandukanya mu buryo burambuye amagerageza yo kuziba imitsi n'ayo gukubita.

Ibyakozwe koko mu buryo bwo kwigana TBI

Nta gerageza ku bantu ryerekeye ubururu bwa metilene mu gukomereka k'ubwonko bitewe n'ihungabana ryatangajwe. Ibyanditswe byose kuri TBI ni ubushakashatsi ku nyamaswa, cyane cyane imbeba nini n'into, kandi byibanda ku itsinda rito ry'amagerageza akwiriye kuvugwa mu mazina, kuko arimo itandukaniro incamake zikunda gusibanganya.

Ubushakashatsi bwa mbere bwo gukubita igice cyo hanze cy'ubwonko mu buryo bugenzurwa bwahaye imbeba nini 1 mg/kg binyuze mu mutsi w'amaraso nyuma y'isaha imwe zikubiswe ku buryo bworoheje, hanyuma 0.5 mg/kg nyuma y'amasaha atatu (Watts, 2014). Ingano y'agace kangiritse yagaragajwe na MRI yakomeje kuba nto kurushaho mu nyamaswa zahawe umuti mu byumweru bibiri zo zakurikiranwe. Gushyira ibirenge aho bitagomba kujya mu igerageza ryo kugenda byagabanutse ku buryo bufite agaciro mu ibarurishamibare ku minsi ya 1, 2 na 7, ariko ntibyabaye ku munsi wa 14. Mu byitegerejwe na mikorosikopi ku munsi wa 14, ingirabuzimafatizo z'imyakura zangirikaga mu gice cyo hanze cy'ubwonko cyakomeretse zabazwe ari 270 ugereranyije na 368 muri buri gace karebwaga, naho izagaragazaga ibara rya Nissl ridasanzwe zari 41 ugereranyije na 73. Mu yandi magambo, habaye kurindwa hakiri kare, ariko akarushyo ku myitwarire kagenda kayoyoka mu cyumweru cya kabiri.

Igerageza ry'igikomere gikwirakwira ryakoresheje mu mbeba nto umuvuduko w'amazi ukubitishwa hagati ku mutwe, hamwe n'ingano imwe ya 2 mg/kg y'umuti yatanzwe mu mutsi w'amaraso mu gihe kitageze ku gice cy'isaha (Fenn, 2015). Inyamaswa zahawe umuti zagaragaje imikorere y'ingirabuzima fatizo igenga ububyimbirwe yagabanutse, ingirabuzimafatizo za microglia ziri mu bub yimbirwe nke kurushaho, kubyimba guke kwagaragaraga, kandi nta myitwarire isa n'iy'agahinda gakabije ku munsi wa 7. Ibyo umuti utahinduye na byo bifite akamaro kangana: igikomere ubwacyo cyongereye amazi yo mu bwonko ku rugero ruto gusa, kandi ubururu bwa metilene ntibwakuyeho kugabanuka kw'ibiro cyangwa intege nke mu guhuza ingendo z'umubiri. Kugabanya ububyimbirwe si kimwe no kurinda mu buryo bwuzuye.

Ubushakashatsi bubiri ku mbeba nto bwakoresheje gahunda imwe: 1 mg/kg nyuma y'isaha imwe, 0.5 mg/kg nyuma y'amasaha atandatu, hanyuma umuti buri munsi mu minsi itatu, kandi bwaguye ibyamenyekanye ku buryo bw'imikorere. Mu buryo bwo gukubita igice cyo hanze cy'ubwonko, umuti wagabanyije ingano y'agace kangiritse nyuma y'amasaha 24, amasaha 72, no ku munsi wa 14, ari na ko urinda ingirabuzimafatizo z'imyakura kandi ukongera ibimenyetso byo kwiyogereza kw'ingirabuzimafatizo (Zhao, 2016). Mu buryo bwo gukubita hakoreshejwe umuvuduko w'amazi, wagabanyije urupfu rw'ingirabuzimafatizo z'imyakura rugengwa n'imikorere yazo, ukomeza urubibi rw'amaraso n'ubwonko rwacagamo ibintu, kandi uzamura amanota y'isuzuma ry'imikorere y'imyakura mu byumweru bibiri (Shen, 2019). Ariko amazi yo mu bwonko ntiyagaragaje itandukaniro nyuma y'amasaha 72 mu bushakashatsi bwa Zhao, kandi ubushobozi bwo kuguma ku nkoni izunguruka ya rotarod ntibwagaragaje itandukaniro ku minsi ya 1 na 3 mu bushakashatsi bwa Shen. Ibipimo by'agace kangiritse no kurokoka kw'ingirabuzimafatizo byarahindutse; ibyerekeye kubyimba n'ubushobozi bwa mbere bwo kugenda si ko buri gihe byahindukaga na byo.

Igerageza ryagaragaye cyane ku byerekeye igihe ni iryatinze gutanga umuti (Watts, 2016). Ryakoresheje bwa buryo bumwe bwo gukubita, ariko ingano ya mbere y'umuti ntiyatanzwe kugeza nyuma y'amasaha 24 hakomeretse. Ku munsi wa 2, itsinda ryahawe umuti ritinze ryagaragaje igabanuka ry'agace kangiritse rigereranywa n'iry'inyamaswa zahawe umuti mu masaha ya mbere, kandi iryo gabanuka ryakomeje ku minsi ya 7 na 14. Ikimenyetso ku myitwarire cyari gifite imbaraga nke kurushaho: kugabanuka kw'amakosa yo gushyira ibirenge aho bitagomba kujya mu itsinda ryahawe umuti ritinze kwari icyerekezo kitageze ku rwego rw'agaciro mu ibarurishamibare. Laboratwari imwe, uburyo bumwe bw'igerageza, igihe kimwe cy'amasaha 24. Ibyo ni ibimenyetso nyakuri by'uko igihe umuti ushobora gutangwamo kirenga amasaha ya mbere, ariko ni na byo bimenyetso byose bishyigikira icyo gitekerezo. Mwitondere umutego uri mu ijambo gutinda mu zindi nyandiko: urukurikirane rw'ubushakashatsi bwo mu Burusiya rwari rufite umutwe werekeye kurinda imyakura gutinze rwatangaga umuti nyuma y'iminota 30, kandi rwakoreshaga gutinda rushaka kuvuga ibisubizo biramba, atari gutangira gutanga umuti bitinze.

Ubushakashatsi buto ku gikomere kiri hamwe mu mbeba nini bwuzuza ishusho y'igihe umuti utangirwa buvuye ku rundi ruhande: gutanga umuti ako kanya mbere yo gukomereka no kuwutanga nyuma y'iminota 30 byombi byagabanyije imikorere mibi y'amaboko n'amaguru (Stelmashook, 2019). Gutanga umuti mbere bikora muri laboratwari neza na neza kubera ko ari yo iteganya igihe cyo gukomereka.

Kwita ku ngano y'umuti ni ingenzi hano. Amasesengura asobanura ko ingano nto zitera imbaraga imikorere yo guhumeka ya mitokondiriya, naho ingano nini zikayibuza gukora, ari yo miterere y'ibice bibiri igaragara mu mikorere y'ubururu bwa metilene muri rusange. Ni yo mpamvu ibisubizo bidashobora gusobanurwa ngo uko ubururu bwiyongera ni ko gusubirana byiyongera. Buri bushakashatsi bugerageza ingingo imwe ku murongo ugaragaza iyo mikorere. Inyandiko isobanura uko igisubizo gihinduka bitewe n'ingano y'umuti ikurikirana uwo murongo mu buryo butandukanye bw'igerageza, naho isuzuma ry'umutekano n'ingaruka mbi rikagaragaza ibyo ingano nini zikora aho gutanga izo nyungu.

Soma iyo mbonerahamwe ugereranya ibyiciro: ikinyabutabire kimwe, ibihe bitatu bitandukanye. Gukumira biri mu murongo wo hagati, kuvura ako kanya mu mirongo ibiri ya mbere, naho ibisubizo bigaragara nyuma biri mu murongo wa mbere n'uwa gatatu.

Gukumira, kuvura ako kanya, ibisubizo bigaragara nyuma

Gukumira ni cyo gitekerezo cyoroshye gusobanura nabi kurusha ibindi. Mu buryo bwo kwigana ibura ry'amaraso, inyamaswa zahawe umuti mbere y'uko umutsi uzibwa zigira ibisubizo byiza kurushaho. Ibyo bisubizo rimwe na rimwe bivugwa nk'aho ubururu bwa metilene burinda ubwonko ubwo ari bwo bwose ikintu cyose cyazabwangiza. Nta kintu nk'icyo bugaragaza. Bugaragaza ko mitokondiriya zateguwe hakoreshejwe indi nzira ya elegitoroni zihanganira neza kurushaho ibura ry'amaraso ryateganyijwe. Nta muntu uteganya gukomereka umutwe.

Kuvura ako kanya ni ho ibimenyetso kuri TBI byibanda. Gutanga umuti mu masaha akurikira gukubitwa byibasira uruhererekane rw'ukwangirika gukurikiraho rukiri kuba: kubura ingufu, ihungabana riterwa n'ubukana bwa ogisijeni, ububyimbirwe, no kubyimba. Ibipimo by'agace kangiritse n'iby'amazi atera kubyimba bigenda neza aha ni ingaruka nyakuri z'umuti, ariko ni ukuvura uruhererekane rw'ibiba, si ugusubiza inyuma ugucika kw'inyama.

Ibisubizo bigaragara nyuma ni cyo gitekerezo cya gatatu. Imyitwarire ipimwe nyuma y'ibyumweru hakomeretse, cyangwa imikoreshereze ya poroteyine ipimwe nyuma y'amezi mu buryo bwo kwigana kwangirika buhoro buhoro, isubiza niba kurindwa kwabaye kare kwarakomeje cyangwa niba inzira zigenda buhoro zarahinduye icyerekezo. Agace kangiritse gato nyuma y'amasaha 24, icyerekezo cy'imyitwarire kidafite agaciro mu ibarurishamibare nyuma yo gutanga umuti watinzeho amasaha 24, no kwitwara neza kurushaho mu nzira z'inzitane nyuma y'amezi yo guhabwa umuti igihe kirekire, ni ibitekerezo bitatu bitandukanye bisaba ibimenyetso bitandukanye, kandi ubu icya mbere gusa ni cyo cyujuje ibisabwa inshuro irenze imwe.

Ibyo ibi bimenyetso bidashobora kugaragaza

Buri gisubizo cyavuzwe haruguru gifite urubibi rumwe. Mitokondiriya z'inyamaswa nto zihekenya zisubiza ku bururu bwa metilene mu buryo mitokondiriya z'abantu zishobora kuba zihuriyeho na zo. Ariko imbeba nini ihawe umuti mu mutsi nyuma y'iminota mike ikubiswe n'imbaraga zapimwe si umuntu ugeze mu ishami ry'ubutabazi bwihuse nyuma y'amasaha aguye. Ikinya, kugenzura ubukana bw'igikomere, inyamaswa zikiri nto kandi zifite ubuzima bwiza, n'igihe gito cyo gukurikirana, byose bigabanya ibishobora kwimurirwa ku bantu. Nta bushakashatsi na bumwe bw'ubururu bwa metilene ku bikomere biterwa n'iturika bubaho, bityo ubwoko bw'igikomere bureba cyane abasomyi bo mu gisirikare ni bwo bufite ibimenyetso bike kurusha ubundi.

Nta n'uburyo bwo guhindura ingano z'umuti kugira ngo zikoreshwe mu bantu butangwa hano. Ubushakashatsi ku nyamaswa bukoresha gutera umuti mu mutsi w'amaraso no mu mwanya wo mu nda, ku ngano zatoranyijwe kugira ngo igerageza rigenzurwe, si ibitonyanga binyobwa bigurishwa mu maduka. Nta na kimwe muri ubu bushakashatsi gishyiraho gahunda y'umuti ku bantu, kandi nta na kimwe hano kigerageza ubururu bwa metilene hamwe n'ubuvuzi busanzwe bw'ibikomere byo ku mutwe.

Bityo incamake ivugisha ukuri ijya mu gika kimwe. Mu nyamaswa nto zihekenya, ubururu bwa metilene butanzwe hafi y'igihe ubwonko bukomerekeye bitewe n'ihungabana cyangwa kubura amaraso burinda umusaruro w'ingufu wa mitokondiriya, kandi uko kurindwa gukurikirwa n'uduce twangiritse duto kurushaho n'amanota meza kurushaho y'isubirana. Ubushakashatsi bumwe bwo gukubita bwagumanye igice cy'ingaruka zo kugabanya agace kangiritse n'igihe ingano ya mbere y'umuti yatanzwe itinzeho amasaha 24. Niba hari na kimwe muri ibyo kiba mu bwonko bw'abantu bwakomeretse ntibirageragezwa, kandi ubushakashatsi kuri TBI na sitroke bugerageza ibihe bitandukanye bukoresheje ibipimo by'ibisubizo bitandukanye. Umuntu wese ugurisha icyizere kidashidikanywaho ashingiye kuri ibi bimenyetso aba yongeyemo ikintu amagerageza atigeze agira.