I-methylene blue namafutha esibindini: okutholwe izifundo zokuhlola

Ukunqwabelana kwamafutha esibindini yigama elilodwa elisetshenziselwa izinkinga eziningana ezihlukene. Komunye umuntu imbangela iwukusebenzisa utshwala obuningi isikhathi eside. Komunye kuba ukungena kwezakhamzimba ngokweqile, okuhambisana nokumelana ne-insulin nokulethwa kwamafutha engeziwe esibindini. Isibonakhulu singabonisa nje ukugcinwa kwamafutha kuzo zombili izimo, kodwa izimbangela zokuqala ziyahluka. Lowo mehluko unquma lokho noma yiluphi ucwaningo lokuhlola olungakufakazela.

Ucwaningo olushicilelwe nge-methylene blue namafutha esibindini luncane, futhi kulo mbuzo lonke lungolwangaphambi kokuhlolwa kubantu. Izifundo ezintathu ezenziwa kumagundane amakhulu namancane yizona ezicashunwa kakhulu, futhi azikhombi zonke ohlangothini olufanayo. Olunye ucwaningo lokuphakela nge-ethanol lwalungisa ushintsho lwe-redox kodwa aluzange lushintshe amafutha esibindini. Olunye ucwaningo lokudla okunamafutha amaningi lwanciphisa amafutha esibindini kanye noshintsho ekudluliselweni kwezimpawu. Olunye ucwaningo ezilwaneni ezinempilo lwathola imiphumela ephambene yokwakheka kwama-peroxide emafutheni esibindini nasezinso. Uma zifundwa ndawonye, lezi zifundo zibonisa ukuthi kungani imiphumela emithathu okufanele ihlolwe kumele igcinwe ihlukene: ushintsho lwe-redox, ukuvuselelwa kokudluliselwa kwezimpawu, nokunqwabelana kwamafutha ezicutshini.

Imiphumela emithathu okulula ukuyididanisa

Isilinganiso se-redox sichaza indlela ama-electron aphathwa ngayo. Isilinganiso se-NAD+ uma iqhathaniswa ne-NADH esibindini sibonisa ukuthi isimo ngaphakathi kwamangqamuzana sitshekele kakhulu ku-oxidation noma ku-reduction. I-oxidation ye-ethanol iguqula i-NAD+ ibe yi-NADH, ngakho ukuphuza utshwala isikhathi eside kwehlisa lesi silinganiso. Udayi owamukela ama-electron ungaphinde usikhuphule. Lokho kuwukusebenza kwamakhemikhali, hhayi ubufakazi bokuthi amafutha agciniwe anciphile.

Isilinganiso sokudluliselwa kwezimpawu sichaza ukulawulwa kwezinqubo. I-SIRT1 iyi-enzyme elawulayo encike ku-NAD+ futhi eguqula amaprotheni ahilelekile ekusebenzeni kwama-mitochondria nasekuphathweni kwamafutha. I-AMPK isebenza njengenzwa yokushoda kwamandla; lapho ivuselelwe, ikhuthaza i-oxidation yezinto ezinikeza amandla futhi inciphise ukwakhiwa kwamafutha. Uma umbiko wocwaningo ubika ukuthi i-methylene blue ivuselele i-SIRT1 esibindini, ubika ushintsho ekulawulweni kwezinqubo. Awukabiki umphumela esigulini.

Isilinganiso sokuhlolwa kwezicubu noma samakhemikhali emzimbeni sichaza isibindi uqobo. Izibonelo ezivamile zihlanganisa inani le-triglyceride ngegremu ngalinye lesicubu, ukufakwa kombala we-Oil Red O emafutheni angathathi hlangothi, ukuhlolwa kokuvuvukala kwamangqamuzana nokulimala kusetshenziswa i-hematoxylin ne-eosin, kanye nomsebenzi we-ALT ku-plasma. Yilesi sigaba sesithathu kuphela esiphendula ukuthi ukunqwabelana kwamafutha esibindini kwaba ngcono yini ngenxa ye-methylene blue kulolo cwaningo.

Ukugcina lezi zigaba zihlukene kuvimbela ukuhunyushwa okungalungile okuvame kakhulu: umphumela omuhle we-redox noma wokudluliselwa kwezimpawu awusho ukuthi amafutha esibindini anciphile.

Imodeli ye-ethanol: i-redox yalungiswa, amafutha awashintshanga

Umphumela ocacile kakhulu ongabonisi inzuzo uvela ocwaningweni lokuphakela amagundane amakhulu angamaduna ohlobo lwe-Wistar nge-ethanol isikhathi eside. Izilwane zanikezwa i-ethanol njengengxenye yokudla okuwuketshezi, eyakhushulwa yafinyelela ku-36 percent wamandla aphelele. Izilwane zokuqhathanisa zanikwa ukudla okulinganayo, kodwa zathola i-glucose esikhundleni samandla avela ku-ethanol. Iqembu elilodwa le-ethanol neqembu elilodwa lokuqhathanisa aphinde athola i-methylene blue engu-130 mg ngelitha ngalinye lokudla, cishe u-42 mg nge-kg ngayinye ngosuku, kusukela osukwini 5 kuya osukwini 30.

Isimo se-redox salinganiswa kusetshenziswa amapheya avamile emikhiqizo yemetabolism: i-lactate uma iqhathaniswa ne-pyruvate ku-cytosol, kanye ne-3-hydroxybutyrate uma iqhathaniswa ne-acetoacetate kuma-mitochondria. Ekuqaleni kokuphakelwa nge-ethanol eningi, amaqembu e-ethanol abonisa izinguquko ezinkulu: isilinganiso se-NAD+ uma iqhathaniswa ne-NADH ku-cytosol sehla cishe ngo-62 percent, kanti kuma-mitochondria sehla cishe ngo-71 percent, kwaphinde kwakhuphuka i-glycerol 3-phosphate. I-methylene blue yaguqula kakhulu lezo zinguquko futhi yabuyisela i-glycerol 3-phosphate eduze kwamanani ezilwane zokuqhathanisa, ngaphandle kokushintsha inani le-ethanol elidliwe, ukwanda kwesisindo somzimba, noma i-ethanol ku-serum.

Amafutha esibindini abonisa indaba ehlukile. Osukwini 12, ngaphambi kokunqwabelana okukhulu kwamafutha, i-triglyceride ayizange ihluke phakathi kwamaqembu. Osukwini 27, amaqembu e-ethanol ayenokwanda okukhulu kwe-triglyceride kungakhathaliseki ukuthi ayethola i-methylene blue yini. Osukwini 30, ama-lipid aphelele anda cishe ngo-89 percent kanti i-triglyceride yanda cishe ngo-196 percent ezilwaneni ezaziphakelwa nge-ethanol; nalapho udayi awuzange ushintshe lokho. Ukunqwabelana kwamafutha phakathi nendawo yezigaxa zesibindi kwakubukeka kufana, kungakhathaliseki ukuthi kwakukhona ukwelashwa yini. Ababhali baphetha ngokuthi ushintsho lwe-redox olubangelwa yi-ethanol alusona isizathu esiyinhloko sokunqwabelana kwamafutha esibindini ngemva kokuphakelwa isikhathi eside kule modeli. Ukufunda ukuhlukanisa ukuthi okutholwe ezilwaneni nasemangqamuzaneni kuhlobana kanjani nobungozi kubantu kuyasiza lapha: indlela yokusebenza ingaba khona ngempela kodwa ingawulawuli umphumela.

Lolu wucwaningo okufanele lucashunwe lapho umuntu ethi noma yikuphi ukulungiswa kwe-redox kufanele kususe amafutha esibindini. Kulolu hlelo lokuhlola, akuzange kwenzeke.

Imodeli yemetabolism: ukudluliselwa kwezimpawu kanye namafutha anciphile, kumagundane amancane

Isithombe esihlukile sivela ocwaningweni lwamangqamuzana esibindi namagundane amancane adla ukudla okunamafutha amaningi, olwalugxile ku-SIRT1 ne-AMPK. Emangqamuzaneni e-HepG2, emangqamuzaneni e-AML-12, nasemangqamuzaneni esibindi ayethathwe ngokuqondile kumagundane amakhulu, i-methylene blue yakhuphula isilinganiso se-NAD+ uma iqhathaniswa ne-NADH, yandisa iphrotheni ye-SIRT1, yanciphisa ukufakwa kwamaqembu e-acetyl kumlawuli i-PGC-1alpha, yandisa inani le-DNA yama-mitochondria nokusetshenziswa komoya-mpilo, futhi yavuselela i-AMPK, okwaholela ekwandeni kwe-CPT-1 ne-PPARalpha. Lapho ukukhiqizwa kwe-SIRT1 kwehliswa, ukuvuselelwa kwe-AMPK kwanyamalala, okuxhumanisa lolu chungechunge ne-SIRT1 kuleso simiso samangqamuzana. Udayi waphinde wamelana nezimpawu ezikhuthaza ukwakheka kwamafutha ezazivela ku-T0901317, okuyisivuseleli se-LXR, nasekuchayekeni ku-palmitate, kuhlanganise nokukhuthazwa kwe-SREBP-1c, i-FAS, ne-ACC.

Ingxenye yezilwane yasebenzisa amagundane amancane angamaduna ohlobo lwe-C57BL/6, aphakelwa ukudla okunamafutha angu-60 percent amasonto angu-8. I-methylene blue yanikezwa ngomlomo izikhathi ezine ngesonto emasontweni angu-4 okugcina, ngenani elingu-3 noma 10 mg nge-kg ngayinye ngosuku. Amagundane ayelashwa abonisa ukufakwa kombala we-Oil Red O okuncane, i-triglyceride ephansi esibindini, ukuvuvukala kwamangqamuzana nokuwohloka okubangelwa amafutha okuncane ekuhlolweni kwezicubu, kanye ne-ALT ephansi ku-plasma kunamagundane adla ukudla okunamafutha amaningi kodwa ayengalashwa. Ucwaningo lokuhamba nokuguqulwa komuthi emzimbeni olukulowo mbiko lwathola ukuthi ukutholakala kwawo emzimbeni ngemva kokunikezwa ngomlomo kwakucishe kube ngu-31 kuya ku-35 percent, nokumuncwa emathunjini okwakucishe kuphelele kodwa kube nokuguqulwa kwawo okukhulu yimetabolism. Isilinganiso esiphezulu kakhulu senani elisezicutshini uma liqhathaniswa neliku-plasma satholakala esibindini, okwenza umphumela esibindini okungenani ube nokwenzeka ngokwendlela into esabalala ngayo emzimbeni.

Lokho kuwuphawu lwangempela lokunciphisa ukunqwabelana kwamafutha, kodwa kunemingcele emincane. Kuwucwaningo olufushane kumagundane amancane, olunezilwane ezingu-9 kuya ku-10 eqenjini ngalinye, uhlobo olulodwa lokudla, amanani amabili omuthi, kanye nokwelashwa kwamasonto amane. Luhlola ukunqwabelana kwamafutha okubangelwa yimetabolism kanye nezici zokuvuvukala kwesibindi okuhambisana namafutha, hhayi isifo esihlobene notshwala. Aluhloli i-cirrhosis, ukubuyiselwa emuva kokwakheka kwezicubu eziyizibazi, noma yimuphi umphumela kubantu. Indima yezilinganiso zama-mitochondria ne-redox ekuchazeni imiphumela enjalo iwukuyikhomba njengokusekela umbono ongakafakazelwa, hhayi njengomthamo noma uhlelo lokwelashwa.

Isithombe sesikhashana sezicubu ezinempilo: umthamo ofanayo, izitho eziphambene

Ucwaningo lwesithathu luvame ukufakwa ezimangalweni eziphathelene nesibindi lapho lungafanele khona. Ocwaningweni lwezinsuku ezingu-30 kumagundane amakhulu ezinsikazi anempilo ohlobo lwe-Wistar, izilwane ezinhlanu zathola i-methylene blue engu-1 mM emanzini okuphuza, kanti ezinhlanu zasebenza njengezilwane zokuqhathanisa. I-superoxide dismutase, i-catalase, ne-glutathione esesimweni se-reduction azizange zishintshe esibindini noma ezinso. Ukwakheka kwama-peroxide emafutheni kwenyuka kancane esibindini futhi kwehla ezinso. I-ALT ne-creatinine ku-serum kwehla, ngaphandle koshintsho ku-nitrogen ye-urea esegazini.

Ukufundwa okuqotho kwalokhu kuwukuthi umphumela uncike esicutshini ezilwaneni ezinempilo, hhayi ukuthi kuwukwelashwa kwesifo. Ukuchayeka okufanayo kwabonakala kukhuthaza i-oxidation kancane ngokwesilinganiso esisodwa esibindini, futhi kuvikela kancane ngokwesilinganiso esifanayo ezinso, kuyilapho izindlela ezivamile zokuzivikela ku-oxidation zahlala zingashintshile. Njengoba kwakunezilwane ezinhlanu eqenjini ngalinye futhi kungekho modeli yesifo, lo mbiko uxwayisa ngokubiza i-methylene blue ngokuthi iyisivikeli esivamile sesibindi ku-oxidation. Uphinde ubonise ukuthi kungani izinguquko zama-enzyme esibindi zidinga umongo wesifo ochazwe ngokucacile ngaphambi kokuthi zisho ukuthuthuka.

Ukuqhathaniswa kwezifundo ezintathu zokuhlola isibindi

Ithebula lenza iphuzu eliyinhloko libonakale. Udayi oluhlaza okwesibhakabhaka ofanayo, kodwa izinqubo zomzimba ezihlukene. Ucwaningo lwe-ethanol luhlukanisa impumelelo ye-redox nokwehluleka ukunciphisa amafutha. Ucwaningo lokudla luhlanganisa ukudluliselwa kwezimpawu nokuncipha kwamafutha kumodeli eyodwa. Ucwaningo lwezilwane ezinempilo lubonisa ukuthi izinkomba ze-redox zingahamba ngezindlela eziphambene kuye ngesitho.

Kungani lokhu kungasekeli isimangalo sokwelashwa

Akukho kulolu cwaningo okwabandakanya abantu abanamafutha esibindini. Imithamo, izindlela zokunikeza into, nobude besikhathi kuyahluka phakathi kwemibiko, futhi akunakuguqulwa kube uhlelo lwabantu ngokumane kushintshwe ngokwesilinganiso. Amaqembu amancane, ikakhulukazi izilwane ezintathu ngesikhathi ngasinye sokulinganisa i-redox ocwaningweni lwe-ethanol nezilwane ezinhlanu eqenjini ngalinye ocwaningweni lwezilwane ezinempilo, ashiya ukungaqiniseki okukhulu. Ubulili, uhlobo lwezilwane, ukwakheka kokudla, nesikhathi sokuqala ukwelashwa uma siqhathaniswa nesikhathi sokulimala konke kuyahluka. Futhi amamodeli amabili esifo amele izimbangela zokuqala ezihlukene, ngakho umphumela omuhle wocwaningo lokudla awukwazi ukulungisa umphumela ongemuhle wocwaningo lwe-ethanol, futhi nokuphambene nalokho kunjalo.

Kunoma ubani okutholakale ukuthi unesifo sesibindi, okubaluleke kakhulu kulolu lwazi ukuqapha kunokulubheka njengendlela yokwelapha. Isifinyezo sezinyathelo zokuqapha nge-methylene blue uma kuthinteke izinso nesibindi sichaza ukuthi kungani ukungasebenzi kahle kwesitho kushintsha imibuzo yokuphepha ngisho noma umbiko wezilwane ubonakala unomphumela omuhle. Yisa kuchwepheshe wezempilo imininingwane yesifo esitholakele, imiphumela yakamuva yaselabhorethri, umkhiqizo oqondile nendlela onikezwa ngayo, nohlu oluphelele lwemithi. Buza ukuthi yibuphi ubufakazi obusekela lowo mkhiqizo ngaleyo njongo kumuntu onalelo zinga lokungasebenzi kahle kwesitho.

Iphuzu eliyinhloko: i-methylene blue yashintsha isimo se-redox esibindini kumodeli eyodwa ye-ethanol ngaphandle kokunciphisa amafutha agciniwe, yavuselela i-SIRT1 ne-AMPK ngenkathi inciphisa amafutha kumodeli eyodwa yemetabolism yamagundane amancane, futhi yabonisa imiphumela ye-redox encike esithweni kumagundane amakhulu anempilo. Lokho kuyizinkomba ezingalandelwa ocwaningweni, hhayi ukwelashwa okuqinisekisiwe kwamafutha esibindini.