Ubururu bwa metilene n'ibinure mu mwijima: ibyo ubushakashatsi bw'igerageza bwabonye

Kwirundanya kw'ibinure mu mwijima ni izina rimwe rikoreshwa ku bibazo bitandukanye. Ku muntu umwe, imbarutso ni ukunywa inzoga nyinshi igihe kirekire. Ku wundi, ni intungamubiri zirenze izikenewe, ziherekejwe no kutitabira insuline neza no kugeza ibinure byinshi ku mwijima. Mikorosikopi ishobora kwerekana ibinure bibitswe gusa muri ibyo bihe byombi, ariko impamvu zibitera ziratandukanye. Iryo tandukaniro ni ryo rigena icyo igerageza iryo ari ryo ryose rishobora kwemeza.

Ubushakashatsi ku bururu bwa metilene n'ibinure mu mwijima ni buke, kandi kuri iki kibazo bwose bwakozwe mbere y'igerageza ku bantu. Ubushakashatsi butatu ku mbeba nini n'imbeba nto ni bwo buvugwa kenshi, kandi ibisubizo byabwo ntibyose byerekeza hamwe. Ubushakashatsi bumwe bwo kugaburira inyamaswa etanolo bwakosoye impinduka ya redox ariko ibinure byo mu mwijima ntibyahinduka. Ubundi bwakoresheje indyo irimo ibinure byinshi bwagabanyije ibinure byo mu mwijima, bijyana n'impinduka mu ihererekanyamakuru. Ubundi ku nyamaswa nzima bwabonye ibisubizo bihabanye bya perokisidasiyo y'ibinure mu mwijima no mu mpyiko. Iyo busomwe hamwe, bwerekana impamvu ibintu bitatu bipimwa bigomba gukomeza gutandukanywa: impinduka ya redox, gutangiza ihererekanyamakuru, no kwirundanya kw'ibinure mu tunyangingo.

Ibintu bitatu bipimwa byoroshye kwitiranya

Igipimo cya redox gisobanura uko elekitironi zitwarwa. Igipimo cya NAD+ ugereranyije na NADH mu mwijima cyerekana niba imimerere yo mu ngirabuzimafatizo yiganjemo okisidasiyo cyangwa redigisiyo. Okisidasiyo ya etanolo ihindura NAD+ ikayigira NADH, bityo kunywa inzoga igihe kirekire bikagabanya icyo gipimo. Irangi ryakira elekitironi rishobora kongera kukizamura. Ibyo ni ubutabire, si gihamya y'uko ibinure bibitswe byagabanutse.

Igipimo cy'ihererekanyamakuru gisobanura igenzura ry'imikorere. SIRT1 ni anzime igenzura imikorere kandi ishingiye kuri NAD+, ihindura poroteyine zigira uruhare mu mikorere ya mitokondiriya no mu gutunganya ibinure. AMPK ikora nk'icyuma cyumva ko ingufu ari nke; iyo ikanguriwe gukora, iteza imbere okisidasiyo y'ibitanga ingufu kandi ikagabanya ikorwa ry'ibinure. Iyo inyandiko y'ubushakashatsi ivuga ko ubururu bwa metilene bwakanguye SIRT1 mu mwijima, iba ivuga impinduka mu igenzura ry'imikorere. Ntabwo iba iratanga ibisubizo ku murwayi.

Igipimo gishingiye ku isuzuma ry'utunyangingo cyangwa ku butabire bw'umubiri gisobanura uko umwijima ubwawo umeze. Ingero zisanzwe ni ingano ya tirigilisiride kuri garama y'utunyangingo, gusiga ibinure bidafite umuriro w'amashanyarazi irangi rya Oil Red O, gukoresha hematoxylin na eosin mu gusuzuma kubyimba kw'ingirabuzimafatizo no kwangirika, n'igikorwa cya ALT muri plasma. Iki cyiciro cya gatatu ni cyo cyonyine gisubiza niba kwirundanya kw'ibinure mu mwijima kwaragabanutse hakoreshejwe ubururu bwa metilene muri iryo gerageza.

Gutandukanya ibi byiciro birinda kwibeshya gukunze kubaho: igisubizo cyiza cya redox cyangwa cy'ihererekanyamakuru ntigisobanura ko ibinure byo mu mwijima byagabanutse.

Igerageza rya etanolo: redox yarakosowe, ibinure ntibyahinduka

Igisubizo gisobanutse cyane kitagaragaza igabanuka ry'ibinure cyavuye mu bushakashatsi bwo kugaburira imbeba nini z'ingabo zo mu bwoko bwa Wistar etanolo igihe kirekire. Inyamaswa zahabwaga etanolo nk'igice cy'indyo y'amazi, ingano yayo ikazamuka ikagera kuri 36 ku ijana by'ingufu zose. Inyamaswa zo kugereranya zahabwaga indyo ingana n'iy'izahabwaga etanolo, ariko zigahabwa gilukoze mu mwanya w'ingufu zaturukaga kuri etanolo. Itsinda rimwe ryahabwaga etanolo n'itsinda rimwe ryo kugereranya yanahabwaga ubururu bwa metilene bungana na 130 mg kuri litiro y'indyo, ni ukuvuga hafi 42 mg kuri kg ku munsi, kuva ku munsi wa 5 kugeza ku munsi wa 30.

Imimerere ya redox yagereranyijwe hakoreshejwe ibipimo bisanzwe by'ibintu bibiri bibiri biva mu mikorere y'umubiri: lactate ugereranyije na pyruvate kuri sitozoli, na 3-hydroxybutyrate ugereranyije na acetoacetate kuri mitokondiriya. Mu ntangiriro zo kugaburira inyamaswa etanolo nyinshi, amatsinda yahabwaga etanolo yagaragaje impinduka zikomeye: igipimo cya NAD+ ugereranyije na NADH muri sitozoli cyagabanutse hafi 62 ku ijana, naho muri mitokondiriya kigabanuka hafi 71 ku ijana, ndetse glycerol 3-phosphate iriyongera. Ubururu bwa metilene bwahinduye cyane izo mpinduka, kandi busubiza glycerol 3-phosphate hafi y'ibipimo by'amatsinda yo kugereranya, budahinduye ingano ya etanolo yafatwaga, kwiyongera kw'ibiro, cyangwa etanolo yo muri serumu.

Ibinure byo mu mwijima byo byagaragaje ibindi. Ku munsi wa 12, mbere yo kwirundanya gukomeye kw'ibinure, tirigilisiride ntizatandukanyaga amatsinda. Ku munsi wa 27, amatsinda yahabwaga etanolo yari afite ukwiyongera gukomeye kwa tirigilisiride, yaba yarahawe ubururu bwa metilene cyangwa atarabuhawe. Ku munsi wa 30, ibinure byose byiyongereye hafi 89 ku ijana, naho tirigilisiride ziyongera hafi 196 ku ijana mu nyamaswa zahabwaga etanolo; na none irangi ntiryagize icyo ribihinduraho. Kwirundanya kw'ibinure hafi y'igice cyo hagati cy'uduce tw'umwijima byasaga kimwe, haba hakoreshejwe ubururu bwa metilene cyangwa butakoreshejwe. Abanditsi banzuye ko impinduka ya redox iterwa na etanolo atari yo mpamvu nyamukuru y'ibinure byo mu mwijima nyuma yo kugaburira inyamaswa igihe kirekire muri ubu buryo bw'igerageza. Kwiga gutandukanya uko ibyabonetse ku nyamaswa no ku ngirabuzimafatizo bifasha gusobanukirwa ingaruka ku bantu ni ingirakamaro hano: uburyo ikintu gikora bushobora kuba nyakuri ariko ntibugene igisubizo cya nyuma.

Ubu ni bwo bushakashatsi bwo kwifashisha igihe umuntu avuga ko gukosora redox uko ari ko kose bigomba gukuraho ibinure byo mu mwijima. Muri iri gerageza, ntibyabaye.

Igerageza ry'imikorere y'umubiri: ihererekanyamakuru n'ibinure bike, mu mbeba nto

Ibisubizo bitandukanye byavuye mu bushakashatsi ku ngirabuzimafatizo z'umwijima no ku mbeba nto zahabwaga indyo irimo ibinure byinshi, bwibanze kuri SIRT1 na AMPK. Mu ngirabuzimafatizo za HepG2, iza AML-12, n'iz'umwijima zakuwe mu mbeba nini, ubururu bwa metilene bwazamuye igipimo cya NAD+ ugereranyije na NADH, bwongera poroteyine ya SIRT1, bugabanya iyongerwaho ry'amatsinda ya acetyl ku mugenzuzi PGC-1alpha, bwongera ingano ya ADN ya mitokondiriya n'ikoreshwa rya ogisijeni, kandi bukangura AMPK, bikurikirwa no kwiyongera kwa CPT-1 na PPARalpha. Igihe SIRT1 yagabanywaga, gukanguka kwa AMPK ntikwabaye, bihuza uru ruhererekane na SIRT1 muri ubwo buryo bw'igerageza ku ngirabuzimafatizo. Irangi ryanarwanyije ibimenyetso biteza ikorwa ry'ibinure byaturukaga kuri T0901317 ikangura LXR no ku gushyira ingirabuzimafatizo muri palmitate, harimo gutuma SREBP-1c, FAS na ACC byiyongera.

Igice cy'ubushakashatsi ku nyamaswa cyakoresheje imbeba nto z'ingabo zo mu bwoko bwa C57BL/6 zagaburiwe indyo irimo ibinure bingana na 60 ku ijana mu byumweru 8. Mu byumweru 4 bya nyuma, zahabwaga ubururu bwa metilene mu kanwa inshuro enye mu cyumweru, ku ngano ya 3 cyangwa 10 mg kuri kg ku munsi. Imbeba nto zabuhabwaga zagaragaje gusigwa guke kwa Oil Red O, tirigilisiride nke mu mwijima, kubyimba guke kw'ingirabuzimafatizo no kwangirika guke guterwa n'ibinure mu isuzuma ry'utunyangingo, na ALT nke muri plasma, ugereranyije n'imbeba nto zahabwaga indyo irimo ibinure byinshi ariko ntizihabwe ubururu bwa metilene. Igice cy'iyo nyandiko cyasesenguye uko umubiri winjiza kandi ugatunganya icyo kinyabutabire cyasanze ingano igera mu maraso nyuma yo gufatwa mu kanwa ari hafi 31 kugeza kuri 35 ku ijana. Hafi y'ingano yose yinjiraga mu mubiri ivuye mu mara, ariko igice kinini kigahindurwa n'imikorere y'umubiri. Umwijima ni wo wari ufite igipimo kinini kurusha ibindi cy'ingano iri mu tunyangingo ugereranyije n'iri muri plasma, ibyo bikaba byibura bituma ingaruka ku mwijima zishoboka urebye uko icyo kinyabutabire gikwirakwira.

Ibyo ni ikimenyetso nyakuri cy'igabanuka ry'ibinure byirundanyije mu mwijima, ariko gifite imipaka migufi. Ni igerageza ry'igihe gito ku mbeba nto, rifite inyamaswa 9 kugeza kuri 10 muri buri tsinda, indyo imwe, ingano ebyiri zitandukanye z'ubururu bwa metilene, n'ibyumweru bine byo kubutanga. Risuzuma kwirundanya kw'ibinure biterwa n'imikorere y'umubiri n'ibiranga ukubyimbirwa kw'umwijima kujyanye n'ibinure, si indwara iterwa n'inzoga. Kandi ntirisuzuma cirrhose, gusubiza inyuma ikorwa ry'inkovu mu mwijima, cyangwa igisubizo icyo ari cyo cyose ku bantu. Uruhare rw'ibipimo bya mitokondiriya na redox mu gusobanura bene ibi bisubizo ni ukubigaragaza nk'ibishyigikira igitekerezo kigomba gusuzumwa, atari nk'ingano yo gufata cyangwa gahunda yo gukoresha.

Isuzuma ry'utunyangingo tuzima: ingano imwe, ingingo zitanga ibisubizo bihabanye

Ubushakashatsi bwa gatatu bukunze kwifashishwa mu bivugwa ku mwijima kandi bidakwiye. Mu igerageza ry'iminsi 30 ku mbeba nini z'ingore nzima zo mu bwoko bwa Wistar, inyamaswa eshanu zahabwaga ubururu bwa metilene bungana na 1 mM mu mazi yo kunywa, naho eshanu zigakoreshwa mu kugereranya. Superoxide dismutase, catalase na glutathione iri mu mimerere ya redigisiyo ntibyahindutse mu mwijima cyangwa mu mpyiko. Perokisidasiyo y'ibinure yiyongereye gato mu mwijima, igabanuka mu mpyiko. ALT na creatinine byo muri serumu byagabanutse, ariko azote ya ureya yo mu maraso ntiyahinduka.

Gusoma ibi mu buryo budahindura icyo bivuga ni ukubona ko ibisubizo biterwa n'utunyangingo twihariye mu nyamaswa nzima, atari ukuvura indwara. Hakoreshejwe ingano imwe, igipimo kimwe cyagaragaje ko mu mwijima hashobora kuba haratejwe okisidasiyo nkeya, naho mu mpyiko hakaboneka uburinzi buke hakurikijwe icyo gipimo, mu gihe uburyo busanzwe bwo kwirinda okisidasiyo butahindutse. Kubera ko buri tsinda ryari rifite inyamaswa eshanu kandi nta buryo bw'igerageza ry'indwara bwakoreshejwe, iyi nyandiko iraburira kwita ubururu bwa metilene ikinyabutabire kirwanya okisidasiyo mu mwijima muri rusange. Inerekana impamvu impinduka z'anzime z'umwijima zigomba gusobanurwa mu rwego rw'indwara izwi neza mbere yo gufatwa nk'ikimenyetso cy'uko ibintu byateye imbere.

Kugereranya amagerageza atatu ku mwijima

Imbonerahamwe igaragaza ingingo y'ingenzi. Irangi ry'ubururu risa, ariko imikorere y'ibinyabuzima iratandukanye. Ubushakashatsi bwa etanolo butandukanya gutsinda mu gukosora redox no kutagabanya ibinure. Ubushakashatsi bw'indyo buhuza ihererekanyamakuru n'igabanuka ry'ibinure mu buryo bumwe bw'igerageza. Ubushakashatsi ku nyamaswa nzima bwerekana ko ibipimo bya redox bishobora guhinduka mu byerekezo bihabanye bitewe n'urugingo.

Impamvu ibi bidatanga gihamya yo kuvura

Nta na bumwe muri ubu bushakashatsi bwakoresheje abantu bafite ibinure mu mwijima. Ingano zatanzwe, inzira byanyuzwemo n'igihe byatanzwe biratandukanye mu nyandiko, kandi ntibishobora guhindurwa gahunda yo gukoresha ku bantu hakoreshejwe gusa kubara ingano ijyanye n'ubunini bw'umubiri. Amatsinda mato, cyane cyane inyamaswa eshatu kuri buri gihe redox yapimwaga mu bushakashatsi bwa etanolo n'eshanu muri buri tsinda mu bushakashatsi ku nyamaswa nzima, asiga gushidikanya gukomeye. Igitsina, ubwoko bw'inyamaswa, ibigize indyo n'igihe ubururu bwa metilene bwatangiwe ugereranyije n'igihe cyo kwangirika byose biratandukanye. Kandi uburyo bubiri bw'igerageza ry'indwara buhagarariye impamvu zitandukanye ziyitera, bityo igisubizo cyiza cy'ubushakashatsi bw'indyo ntigishobora gukosora igisubizo kitari cyiza cy'ubushakashatsi bwa etanolo, cyangwa ngo bibe mu buryo bunyuranye.

Ku muntu wese wasuzumwe agasanganwa indwara y'umwijima, icyihutirwa ni ugusoma yibanda ku kwitondera, aho kwibanda ku kuvura. Incamake y'ibyitonderwa ku mpyiko no ku mwijima ku byerekeye ubururu bwa metilene isobanura impamvu imikorere mibi y'urugingo ihindura ibibazo by'umutekano, nubwo inyandiko y'ubushakashatsi ku nyamaswa yaba isa n'itanga ibisubizo byiza. Shyira umuvuzi amakuru y'indwara wasanganywe, ibisubizo bya laboratwari bya vuba, igicuruzwa nyacyo n'inzira kinyuzwamo, n'urutonde rwuzuye rw'imiti ufata, maze umubaze ibimenyetso bishyigikira gukoresha icyo gicuruzwa kuri iyo ntego ku muntu ufite urwo rwego rw'imikorere mibi y'urugingo.

Muri make: ubururu bwa metilene bwahinduye imimerere ya redox y'umwijima mu gerageza rimwe rya etanolo butagabanyije ibinure bibitswe, bukangura SIRT1 na AMPK bunagabanya ibinure mu gerageza rimwe ry'imikorere y'umubiri ku mbeba nto, kandi bugaragaza ingaruka za redox zihariye kuri buri rugingo mu mbeba nini nzima. Ibyo ni inzira zo gukurikirana mu bushakashatsi, si uburyo bwemejwe bwo kuvura ibinure mu mwijima.