Ubururu bwa metilene no kubona: icyo ubushakashatsi kuri iretine bwerekana n'aho bugarukira

Umusomyi abonye ubushakashatsi bwagaragaje ko ubururu bwa metilene bwarinze iretine, maze akibaza ikibazo cyumvikana: bukwiye gushyirwa mu jisho? Ubushakashatsi ku bururu bwa metilene no kubona ntibusubiza icyo kibazo, kuko nta na bumwe mu bushakashatsi bw'ingenzi bwagerageje ubwo buryo bwo kubukoresha. Bumwe bwateye iryo rangi mu gice cy'ijisho cyuzuyemo ibintu bimeze nk'igikoma kibonerana mu mbeba, hamwe n'uburozi. Ubundi bwabushyize mu ruvange rwari rukikije uturemangingo twatandukanyijwe n'umubiri tukashyirwa mu gikoresho cya laboratwari. Ubundi bwabushyize mu mazi yo kunywa y'imbeba zifite ihinduka mu ngirabuzima. Buri gisubizo kigarukira ku nzira yakoreshejwe no ku buryo bw'igerageza cyabonetsemo.

Iyi nyandiko isobanura ubushakashatsi butatu bwabanjirije igeragezwa ku bantu, ubwoko bubiri bw'uturemangingo twa iretine, n'umupaka uri hagati yo kurinda uturemangingo muri laboratwari no kuvura amaso ku barwayi. Ibyagaragaye birahuye: ubururu bwa metilene bushobora guhindura imihangayiko ya mitokondiriya mu turemangingo twa iretine mu bihe bigenzuwe, kandi ibyo ntibitanga impamvu yo gushyira mu maso ibisukika bibugizwe bigurishwa.

Ubwoko bubiri bw'uturemangingo, indwara ebyiri zitandukanye

Iretine igizwe n'ibice byinshi bigerekeranye, kandi igice kiri kuvugwa gifite akamaro. Urumuri rubanza kugera ku turemangingo turwakira mu gice cy'inyuma cya iretine. Ibimenyetso byatwo binyura mu turemangingo tw'imyakura turi hagati bikagera ku turemangingo twa gangiliyoni mu gice cy'imbere cya iretine; amashami maremare yatwo asohoka anyuze mu mutsi wo kubona. Igishushanyo gikurikira cyerekana ibyo bice uko bikurikirana.

Uturemangingo twa gangiliyoni two muri iretine ni two twibasirwa muri glokoma no mu ndwara z'umutsi wo kubona. Iyo ubushakashatsi bwo kuri interineti buvuga ubururu bwa metilene na glokoma, akenshi buba buvuga iki gice cy'imbere n'amashami maremare y'uturemangingo twacyo. Uturemangingo twakira urumuri ni two twibasirwa n'iyangirika ry'igice cy'inyuma cya iretine. Ni two dukenera ingufu nyinshi kurusha utundi muri iretine, kandi dukorera hafi y'urugero ntarengwa rw'ubushobozi bwatwo bwo guhumeka kw'uturemangingo. Ibyo bituma dusigarana ubushobozi buke bwo kwifashisha igihe komplegisi I ya mitokondiriya idakora neza. Icyagaragaye mu bwoko bumwe bw'uturemangingo ntigihita gikoreshwa ku bundi, kandi ubushakashatsi butatu bukurikira burabitandukanya. Uburyo rusange bwo gutandukanya uburyo bw'igerageza n'imyanzuro busobanurwa mu nyandiko ivuga uko wasoma ubushakashatsi ku bururu bwa metilene.

Uturemangingo twa gangiliyoni mu jisho ry'imbeba ikiri nzima

Mu bushakashatsi bwabanje muri ubu butatu, abashakashatsi biganye indwara y'umutsi wo kubona batera rotenone n'urushinge ruto mu gice cy'ijisho ry'imbeba cyuzuyemo ibintu bimeze nk'igikoma kibonerana, bakoresha irindi jisho nk'iryo kugereranya ryatewe gusa uruvange rutwara icyo kinyabutabire. Rotenone ihagarika komplegisi I ya mitokondiriya, ahinjirira ubutumwa bw'amashanyarazi butwarwa na elegitoroni zivuye kuri NADH zigakomeza ahandi. Imikorere mibi ya komplegisi I ni na yo ihuza ubu buryo bw'igerageza n'indwara y'umutsi wo kubona ya Leber ikomoka ku ruhererekane rw'ibisekuru, indwara yibasira uturemangingo twa gangiliyoni n'umutsi wo kubona.

Nyuma y'amasaha makumyabiri n'ane, igice cy'uturemangingo twa gangiliyoni mu maso yatewe rotenone cyari cyarabaye gito mu mubyimba kandi kirimo uturemangingo duke ugereranyije n'amaso yakoreshejwe mu kugereranya. Igihe ubururu bwa metilene bwaterwaga hamwe na rotenone, uko kwangirika kwarakumiriwe ku buryo bwagenderaga ku ngano yatanzwe; ingano nini kurusha izindi zageragejwe (0.07 mg/kg, iri hasi cyane ya LD50 y'imbeba) yarinze umubyimba n'umubare w'uturemangingo. Ibizamini byakorewe icyarimwe ku ruvange rw'ubwonko bwajanjaguwe byerekanye ingaruka ebyiri: ubururu bwa metilene bwagaruye imihangayiko iterwa n'oksidasiyo yari yatewe na rotenone ku rugero rusanzwe, bunakuraho igabanuka ry'ikoreshwa rya ogisijeni. Abanditsi batanze igitekerezo cy'uburyo bushingiye ku kwangirika guterwa no gukangurwa gukabije kw'uturemangingo tw'imyakura: rotenone yangiza uturemangingo twa amacrine tugenzura ibimenyetso, uturemangingo twa gangiliyoni tugatanga ibimenyetso birenze urugero, maze igikorwa cyo kurwanya oksidasiyo kigahagarika ibyangirika bikurikiraho. Imikorere y'ubutabire yatekerejwe ko itera ubwo burinzi isobanurwa birambuye mu nyandiko ivuga uburyo ubururu bwa metilene bukora muri mitokondiriya.

Ibyo bisubizo bifite imbibi eshatu. Irangi ryatewe hamwe n'uburozi mu jisho ubwaryo, bikaba ari uburyo bwo kurigezayo, atari gahunda y'ubuvuzi. Igihe cyo gukurikirana cyari amasaha 24. Kandi ibipimo bya sitokorome ogisidaze byazamutse mu matsinda yombi yari yakomeretse; abanditsi babifashe nk'ikimenyetso cy'imikorere irenze urugero aho kuba gihamya y'uko uguhumeka kw'uturemangingo kwari kwasubijwe mu iretine ikiri nzima.

Uturemangingo twa gangiliyoni twatandukanyijwe n'umubiri tugashyirwa mu gikoresho cya laboratwari

Ubushakashatsi bwa kabiri ntibwakoresheje ijisho ryose. Abashakashatsi batandukanyije uturemangingo twa gangiliyoni two muri iretine n'umubiri w'imbeba nto, batubanza kutugabanya mu bwoko bw'uturemangingo dukomeza kororoka ubuziraherezo, maze batugaragariza rotenone, staurosporine itera urupfu rw'uturemangingo rugenzurwa n'umubiri, cyangwa amasaha 72 ya ogisijeni nke, hanyuma bapima uko twakomeje kubaho bakoresheje irangi ritandukanya uturemangingo tuzima n'utwapfuye. Ubururu bwa metilene ku rugero rwa 1 na 10 micromolar mu ruvange rutungirwamo uturemangingo bwongereye uko twakomeje kubaho imbere ya buri kintu cyangiza, hafi inshuro 1.5 kugeza kuri 1.9 bitewe n'imiterere y'igerageza. Ikizamini cyakozwe hamwe n'ubwo bushakashatsi cyerekanye ko ubururu bwa metilene bwarinze imikorere ya sitokorome c ogisidaze igihe uturemangingo twagaragarizwaga perogiside ya hidirojeni.

Ubu ni ubushakashatsi ku mikorere y'ibinyabutabire ku turemangingo twatandukanyijwe n'umubiri. Ikinyabutabire cyageze ku turemangingo gikwirakwiriye mu ruvange rutungirwamo uturemangingo ku rugero rw'ubwinshi ruzwi, nta gahu kabonerana ko ku nkengero z'imbere z'ijisho, nta ruhande rw'amarira, nta ndorerwamo y'ijisho, nta bintu bimeze nk'igikoma kibonerana byo mu jisho, nta maraso aritunga, cyangwa ubwirinzi bw'umubiri biri mu nzira. Uko koroshya ibintu ni cyo ubu buryo bw'igerageza bugamije: bwerekana ko uturemangingo twa gangiliyoni ubwato dushobora kurindwa igihe ikinyabutabire kitugezeho. Ntibugira icyo buvuga ku kuba igitonyanga gishyizwe ku gahu kabonerana ko imbere y'ijisho cyageza urugero rw'ubwinshi ruzwi ku gice cy'imbere cya iretine. Ubwinshi burenze 10 micromolar bwaririnzwe kubera uburozi ku turemangingo tumwe, bikibutsa ko isano hagati y'ingano yatanzwe n'igisubizo cy'uturemangingo mu gikoresho cya laboratwari ishobora kujya mu byerekezo byombi.

Uturemangingo twakira urumuri mu mbeba zifite ihinduka mu ngirabuzima no mu bwoko bw'uturemangingo bwororerwa muri laboratwari

Ubushakashatsi bwa gatatu bureba igice cy'inyuma cya iretine. Abashakashatsi bakoresheje imbeba za Harlequin, zifite ibura rya poroteyine itera urupfu rw'uturemangingo rugenzurwa n'umubiri, bigatuma komplegisi I iteranywa mu buryo butuzuye, maze basuzuma imiterere y'uturemangingo twakira urumuri, ibimenyetso by'ibice byatwo by'inyuma, n'uko mitokondiriya zari zimeze igihe izo mbeba zari zifite amezi 11. Ubururu bwa metilene bwatanzwe mu buryo bugera mu mubiri wose binyuze mu mazi yo kunywa nyuma yo gucuka, hafi 10 mg/kg ku munsi. Imbeba zifite iryo hinduka zahawe ubururu bwa metilene zagumanye umubyimba munini kurushaho wa iretine, ibimenyetso byinshi kurushaho bya rodopsine na opsine, n'imiterere ya mitokondiriya irushijeho kuba myiza ugereranyije n'imbeba zifite iryo hinduka zitabuherewe.

Ubushakashatsi ku turemangingo bwakozwe hamwe na bwo bwakoresheje uturemangingo twa 661W, ubwoko bw'uturemangingo tw'imbeba dusa n'utwakira urumuri kandi twahinduwe ngo dukomeze kororoka, bwagaragarijwe rotenone iri kumwe cyangwa itari kumwe n'ubururu bwa metilene mu gihe cy'amasaha 24. Uko uturemangingo twakomeje kubaho kwarushijeho kuba kwiza kuri 30 micromolar, kandi ubwinshi buri hasi y'ubwo bwagaruye isano ya NADH kuri NAD+ ku rugero rusanzwe bugabanya n'imihangayiko iterwa n'oksidasiyo. Ikintu gitangaje ni icyo ubururu bwa metilene butakoze: ntibwagaruye ATP. Uburinzi bwajyanaga no kugabanuka kw'imihangayiko y'igabanya n'iyongera rya elegitoroni no gutuza kw'inzira z'uturemangingo zisubiza iyo mihangayiko, harimo igisubizo cya mitokondiriya ku maporoteyine atizingiye neza n'ibimenyetso byo gusenya mitokondiriya, aho kuba ukugarura itangwa ry'ingufu.

Iryo tandukaniro rifite akamaro ku bivugwa ku bururu bwa metilene na iretine. Ikinyabutabire gishobora gutuma akaremangingo kakira urumuri kari mu mihangayiko gakomeza kubaho kitakemuye ibura ry'ingufu zako. Ibyo bituma ibisobanuro by'ubuvuzi bishobora kubutangwa bigarukira ku mihangayiko y'igabanya n'iyongera rya elegitoroni, aho kuba ukugarura imikorere myiza muri rusange.

Kugereranya ubwo bushakashatsi butatu

Igereranya rikurikira rigaragaza uburyo bw'igerageza n'inzira yo gutanga ubururu bwa metilene muri buri bushakashatsi, kuko izo nkingi ebyiri ari zo zigena icyo ibisubizo bishobora gushyigikira.

Buri murongo ureba ubushakashatsi bwabanjirije igeragezwa ku bantu. Nta murongo n'umwe urimo abarwayi, wapimye ubushobozi bwo kubona, cyangwa wagerageje umuti wateguriwe gukoreshwa mu maso.

Impamvu ubu atari ubuvuzi bwa glokoma

Ubuvuzi bwa glokoma bugabanya umuvuduko w'imbere mu jisho. Kurinda uturemangingo tw'imyakura bigamije ikindi: gutuma uturemangingo twa gangiliyoni n'amashami maremare yatwo bikomeza kubaho mu mihangayiko. Ubushakashatsi bwavuzwe haruguru buri mu gikorwa cya kabiri, si icya mbere. Nta na bumwe bwagabanyije umuvuduko, kandi nta na bumwe bwagereranyije ubururu bwa metilene n'ubuvuzi bugabanya umuvuduko. Ni yo mpamvu uburyo busanzwe bwo kuvura glokoma no kugenzura umuvuduko bukomeza kuba ikibazo gitandukanye no kurinda uturemangingo tw'imyakura hagenzurwa igabanya n'iyongera rya elegitoroni, kandi ni yo mpamvu igisubizo cy'uko uturemangingo twakomeje kubaho kidashobora gufatwa nk'uko ubushobozi bwo kubona bwarinzwe.

Itandukaniro ry'inzira zo kubutanga rishimangira icyo gitekerezo. Gutera ikinyabutabire hamwe n'ikindi mu gice cy'ijisho kirimo ibintu bimeze nk'igikoma kibonerana bishyira ingano izwi iruhande rwa iretine igihe cyo kwangirika. Kukinyuza mu mazi yo kunywa bituma umubiri wose w'inyamaswa ukigerwaho mu gihe cy'amezi, ariko ubwinshi bwacyo muri iretine butazwi. Uruvange rutungirwamo uturemangingo rugishyira ku turemangingo twambaye ubusa mu buryo butaziguye. Nta na bumwe muri ubwo buryo buteganya igice cy'ingano ishyizwe ku buso bw'ijisho cyakwambuka agahu kabonerana karyo, ntigikurweho n'amarira, kikanyura mu ndorerwamo y'ijisho no mu gice kirimo ibintu bimeze nk'igikoma kibonerana, maze kikagera kuri kimwe mu bice bya iretine ku rugero rw'ubwinshi rufasha. Icyo kibazo cyo kuhageza ikinyabutabire kiri mu kibazo cyagutse cy'inzira n'ikwirakwira ry'ubururu bwa metilene, aho buri nzira ikenera ibipimo byayo bwite by'ubwinshi bw'ikinyabutabire.

Itandukaniro ry'uduce tugize ijisho ryongeraho inzitizi ya kabiri. Irangi rigeze imbere ku jisho ntiriba rigeze inyuma yaryo, kandi ubwinshi bufasha igice kimwe bushobora kwangiza ikindi. Ibisukika bigurishwa ntibikorwa, ntibivanwamo mikorobe, ntibiringanizwa ngo bigumane pH, cyangwa ngo birindwe kwangirika nk'imiti yateguriwe amaso. Ubuziranenge, pH, osmolality n'ibindi bintu byongerwamo byose bifite akamaro iyo bigiye kugera ku gahu kabonerana k'ijisho cyangwa imbere muri ryo. Nta kintu na kimwe muri ibi byagaragaye kuri iretine cyemeza gushyira ibyo bisukika mu jisho cyangwa ku buso bwaryo. Ibibazo byerekeye ibipimo ngenderwaho byo kubitegura birebana n'umutekano n'uko ubururu bwa metilene bukoreshwa.

Aho ibimenyetso bigarukira

Iyo izo nyandiko eshatu zisomwe hamwe, zishyigikira igitekerezo gifite imbibi: mu bihe bigenzuwe, ubururu bwa metilene bushobora kugabanya imihangayiko y'igabanya n'iyongera rya elegitoroni muri mitokondiriya z'uturemangingo tw'imyakura two muri iretine, bukarinda n'imiterere yatwo. Icyo gitekerezo kigarukira aho ibyo bihe bigarukira. Uburyo bw'igerageza bukoresha uburozi cyangwa inenge ya komplegisi I ikomoka ku ngirabuzima ntibuhwanye na glokoma, udusigazwa twa drusen, cyangwa indwara iterwa na diyabete. Ibihe bigufi byo gukurikirana n'ibipimo by'imyubakire ntibihwanye n'ubushobozi bwo kubona bukomeza kuramba. Kandi ubwinshi burinda mu gice kimwe ntibuba ari ingano yo gutanga mu kindi.

Gihamya ikomeye kurushaho yakenera ibintu bitandukanye: ubwinshi buzwi bugera kuri iretine nyuma yo gukoresha inzira ishobora gukoreshwa mu buvuzi, ibipimo by'ubushobozi bwo kubona bukora mu nyamaswa, inyungu itagendera ku kugabanya umuvuduko mu buryo bw'igerageza bufitanye isano na glokoma, hanyuma amakuru y'umutekano n'imikorere ku bantu. Kugeza ibyo bibonetse, ubururu bwa metilene no kubona bikomeza kuba igitekerezo cy'ubushakashatsi gifite imbibi zisobanutse: imikorere ishoboka y'ikinyabutabire kuri mitokondiriya zo muri iretine, yagaragajwe gusa mu turemangingo no mu nyamaswa, nta nzira iva muri ubu bushakashatsi igana ku kuvura amaso.