Uphononongo lobungqina ngemethylene blue nesibindi esinamafutha

Isibindi esinamafutha ligama elinye elisetyenziswa kwiingxaki ezininzi ezahlukileyo. Komnye umntu, unobangela kukusela utywala obuninzi ixesha elide. Komnye, kukufumaneka kwezondlo ezigqithisileyo kunye nokungaphenduli kakuhle kwi-insulin nokufika kwamafutha ongezelelekileyo esibindini. Imakroskopu inokubonisa ukugcinwa kwamafutha okulula kuzo zombini ezi meko, kodwa oonobangela bokuqala bahlukile. Lo mahluko umisela oko naluphi na uvavanyo olunokukubonisa.

Uncwadi lophando ngemethylene blue nesibindi esinamafutha luncinci, yaye kulo mba luphelele kwizifundo zangaphambi kovavanyo ebantwini. Izifundo ezintathu ezenziwe kwiimpuku neempukwana zezona zikhankanywa rhoqo, yaye azikhombisi zonke kwicala elinye. Esinye isifundo sokondla ngeethanol salungisa utshintsho lwe-redox kodwa amafutha esibindini ahlala engatshintshanga. Esinye isifundo sokutya okunamafutha amaninzi sanciphisa amafutha esibindini kunye notshintsho ekuhanjisweni kwemiqondiso. Esinye isifundo kwizilwanyana ezisempilweni safumanisa iziphumo ezichaseneyo ze-peroxidation yeelipidi esibindini nasezintsweni. Xa zifundwa kunye, zibonisa ukuba kutheni iziphumo ezintathu kufuneka zigcinwe zahlukene: utshintsho lwe-redox, ukuvuselelwa kokuhanjiswa kwemiqondiso, nokuqokelelana kwamafutha kwizicubu.

Iziphumo ezintathu ekulula ukuzibhidanisa

Umlinganiselo we-redox uchaza indlela eziphathwa ngayo ii-electron. Umlinganiselo we-NAD+ ne-NADH esibindini ubonisa ukuba imeko engaphakathi kweeseli ityekele ngakumbi kwi-oxidation okanye kwi-reduction. I-oxidation yeethanol iguqula i-NAD+ ibe yi-NADH, ngoko ukusela ixesha elide kuyawuthoba lo mlinganiselo. Idayi eyamkela ii-electron inokuwunyusa kwakhona. Leyo yikhemistri, ayibobungqina bokuba amafutha agciniweyo anciphile.

Umlinganiselo wokuhanjiswa kwemiqondiso uchaza ulawulo. I-SIRT1 yi-enzyme yolawulo exhomekeke kwi-NAD+ etshintsha iiproteni ezibandakanyeka ekusebenzeni kweemitochondria nasekuphathweni kweelipidi. I-AMPK isebenza njengesivamvo samandla aphantsi, esikhuthaza i-oxidation yamafutha nezinye izibaso kwaye sithintele ukwenziwa kweelipidi xa sivuselelwe. Xa iphepha lophando lichaza ukuvuselelwa kwe-SIRT1 esibindini yimethylene blue, lichaza utshintsho kulawulo. Alikachazi siphumo kwisigulana.

Umlinganiselo wohlolo lwezicubu okanye webhayokhemistri uchaza isibindi ngokwaso. Imizekelo eqhelekileyo sisixa se-triglyceride ngegram nganye yezicubu, ukufakwa kwebala le-Oil Red O kumafutha angathathi cala, uhlolo lokudumba kweeseli nokwenzakala kusetyenziswa ihematoxylin neeosin, kunye nomsebenzi we-ALT kwiplasma. Lolu didi lwesithathu kuphela oluphendula umbuzo wokuba ukuqokelelana kwamafutha esibindini kuye kwancipha kusini na ngenxa yemethylene blue kolo vavanyo.

Ukugcina ezi ndidi zahlukene kuthintela eyona mpazamo ixhaphakileyo yokutolika: isiphumo esihle se-redox okanye sokuhanjiswa kwemiqondiso asithethi ukuba amafutha esibindini anciphile.

Imodeli yeethanol: i-redox ilungisiwe, amafutha awatshintshanga

Esona siphumo sicacileyo sokungabikho kwenzuzo sivela kwisifundo sokondla ngeethanol ixesha elide kwiimpuku ze-Wistar eziyindoda. Izilwanyana zafumana iethanol njengenxalenye yokutya okungulwelo, inyuswa de yaba yi-36 ekhulwini yamandla ewonke. Izilwanyana zolawulo ezazondliwa ngezixa ezilinganayo zafumana iglucose endaweni yamandla avela kwiethanol. Elinye iqela leethanol nelinye iqela lolawulo afumana nemethylene blue eyi-130 mg ngelitha yokutya, malunga ne-42 mg nge-kg ngosuku, ukususela kusuku lwe-5 ukuya kusuku lwe-30.

Imeko ye-redox yaqikelelwa ngezibini eziqhelekileyo zeemetabolite: ilactate nepyruvate kwi-cytosol, kunye ne-3-hydroxybutyrate ne-acetoacetate kwiimitochondria. Ekuqaleni kokondla ngeethanol eninzi, amaqela eethanol abonisa utshintsho olukhulu: umlinganiselo we-NAD+ ne-NADH kwi-cytosol wehla malunga ne-62 ekhulwini, oweemitochondria wehla malunga ne-71 ekhulwini, yaye i-glycerol 3-phosphate yanda. Imethylene blue yalubuyisela umva ubukhulu becala olo tshintsho yaza yabuyisela i-glycerol 3-phosphate kufutshane namaxabiso eqela lolawulo, ngaphandle kokutshintsha isixa seethanol esisetyenzisiweyo, ukwanda kobunzima bomzimba, okanye iethanol kwiserum.

Amafutha esibindini abonisa umfanekiso owahlukileyo. Ngosuku lwe-12, ngaphambi kokuqokelelana okukhulu kwamafutha, i-triglyceride ayizange yahluke phakathi kwamaqela. Ngosuku lwe-27, amaqela eethanol ayenokwanda okukhulu kwe-triglyceride, nokuba ayefumene imethylene blue okanye hayi. Ngosuku lwe-30, iilipidi zizonke zanda malunga ne-89 ekhulwini ne-triglyceride malunga ne-196 ekhulwini kwizilwanyana ezondliwa ngeethanol, kwakhona zingachatshazelwanga yidayi. Ukungena kwamafutha kwiindawo ezisembindini weelobule zesibindi kwakubonakala kufana nokuba lukhona okanye alukho unyango. Ababhali bagqiba kwelokuba utshintsho lwe-redox olubangelwa yiethanol alungoyena nobangela uphambili wesibindi esinamafutha emva kokondliwa ixesha elide kule modeli. Ukufunda ukwahlula indlela iziphumo zezilwanyana neeseli ezinxulumana ngayo nomngcipheko ebantwini kuyanceda apha: indlela yokusebenza inokubakho ngokwenene kodwa ingasilawuli isiphumo.

Esi sisifundo ekufuneka sicatshulwe xa umntu esithi naluphi na ulungiso lwe-redox kufuneka lususe amafutha esibindini. Kolu yilo lovavanyo, aluzange luwasuse.

Imodeli yemetabolism: imiqondiso kunye namafutha ambalwa, kwiimpukwana

Umfanekiso owahlukileyo uvela kwisifundo seeseli zesibindi neempukwana ezondliwa ngokutya okunamafutha amaninzi esigxile kwi-SIRT1 ne-AMPK. Kwiiseli ze-HepG2, kwiiseli ze-AML-12, nakwiiseli zesibindi ezithathwe ngqo kwiimpuku, imethylene blue yanyusa umlinganiselo we-NAD+ ne-NADH, yandisa iproteni ye-SIRT1, yanciphisa ukufakwa kwamaqela e-acetyl kumlawuli i-PGC-1alpha, yandisa isixa se-DNA yeemitochondria nokusetyenziswa kweoksijini, yaza yavuselela i-AMPK, okwalandelwa kukwanda kwe-CPT-1 ne-PPARalpha. Xa ukubonakaliswa kwe-SIRT1 kwancitshiswa, ukuvuselelwa kwe-AMPK kwaphela, nto leyo enxulumanisa olu landelelwano ne-SIRT1 kule nkqubo yeeseli. Idayi yaphikisana nemiqondiso yokwenziwa kwamafutha evela kwi-agonist ye-LXR eyi-T0901317 nasekuchanabekeni kwipalmitate, kuquka ukukhuthazwa kwe-SREBP-1c, i-FAS, ne-ACC.

Inxalenye yezilwanyana yasebenzisa iimpukwana ze-C57BL/6 eziyindoda, ezondliwa ngokutya okunamafutha angama-60 ekhulwini kangangeeveki ezi-8. Imethylene blue yanikwa ngomlomo kane ngeveki kwiiveki ezi-4 zokugqibela, nge-3 okanye i-10 mg nge-kg ngosuku. Iimpukwana ezafumana unyango zabonisa ukufakwa kwebala le-Oil Red O okuncinci, i-triglyceride esibindini ephantsi, ukudumba kweeseli nokuwohloka okunxulumene namafutha okuncinci kuhlolo lwezicubu, ne-ALT kwiplasma ephantsi kunaleyo yeempukwana ezondliwa ngokutya okunamafutha amaninzi ezingafumananga nyango. Uphando lokufunxwa, ukusasazwa nokucutshungulwa kwechiza emzimbeni kwelo phepha lwafumanisa ukuba ukufumaneka kwalo emzimbeni xa linikwe ngomlomo kwakumalunga ne-31 ukuya kwi-35 ekhulwini. Lalifunxwa phantse ngokupheleleyo emathunjini kodwa licutshungulwa kakhulu yimetabolism, yaye owona mlinganiselo uphezulu phakathi kwezicubu neplasma wawusesibindini. Oku kwenza ukuba impembelelo esibindini ibe nokwenzeka ubuncinane ngokwendlela elisasazwa ngayo.

Lo ngumqondiso wokwenene wokuncipha kokuqokelelana kwamafutha, kodwa imida yawo imxinwa. Luvavanyo olufutshane kwiimpukwana, olunezilwanyana ezi-9 ukuya kwezili-10 kwiqela ngalinye, uhlobo olunye lokutya, iidosi ezimbini, neeveki ezine zonyango. Luvavanya ukuqokelelana kwamafutha okubangelwa yimetabolism kunye neempawu zokudumba kwesibindi okunxulumene namafutha, hayi isifo esinxulumene notywala. Aluvavanyi i-cirrhosis, ukubuyiselwa umva kwe-fibrosis, okanye nasiphi na isiphumo ebantwini. Indima yemilinganiselo yeemitochondria ne-redox ekutolikeni iziphumo ezinjalo kukuzibonisa njengobungqina obuxhasa ingcinga yophando, kungekhona njengedosi okanye inkqubo yonyango.

Umfanekiso wezicubu ezisempilweni: idosi efanayo, amalungu achaseneyo

Isifundo sesithathu sidla ngokufakwa kumabango ngesibindi apho singafanelekanga khona. Kuvavanyo lweentsuku ezingama-30 kwiimpuku ze-Wistar ezizimazi ezisempilweni, izilwanyana ezintlanu zafumana imethylene blue eyi-1 mM emanzini okusela, yaye ezintlanu zasebenza njengeqela lolawulo. I-superoxide dismutase, icatalase, neglutathione ekwimo ye-reduction azizange zitshintshe esibindini okanye ezintsweni. I-peroxidation yeelipidi yanda kancinane esibindini yaza yehla ezintsweni. I-ALT necreatinine kwiserum zehla, kodwa initrogen ye-urea egazini ayitshintshanga.

Ukutolika ngokunyanisekileyo kukuba impembelelo yahluka ngokwezicubu kwizilwanyana ezisempilweni, kungekhona ukuba sisinyango sesifo. Ukuchanabeka okufanayo kwabonakala kukhuthaza i-oxidation kancinane esibindini ngokomlinganiselo omnye, kwaye kukhusela kancinane ezintsweni ngokwaloo mlinganiselo, ngoxa iindlela eziqhelekileyo zokuzikhusela kwi-oxidation zahlala zingatshintshanga. Ngezilwanyana ezintlanu kwiqela ngalinye kwaye kungekho modeli yesifo, eli phepha lilumkisa ngokubiza imethylene blue njenge-antioxidant yesibindi ngokubanzi. Likwabonisa ukuba kutheni utshintsho lwee-enzyme zesibindi lufuna imeko yesifo echazwe ngokucacileyo ngaphambi kokuba luthethe ukuphucuka.

Uthelekiso lweemvavanyo ezintathu zesibindi

Imodeli nezilwanyana	Ukuchanabeka	Imilinganiselo ye-redox	Iziphumo zamafutha nokwenzakala
Ukutya okungulwelo okuneethanol ixesha elide, iimpuku ze-Wistar eziyindoda, izilwanyana zolawulo ezondliwa ngezixa ezilinganayo, iintsuku ezingama-30	Imethylene blue eyi-130 mg nge-L yokutya, malunga ne-42 mg nge-kg ngosuku	Umlinganiselo we-NAD+ ne-NADH kwi-cytosol nakwiimitochondria ubuyiselwe ubukhulu becala; i-glycerol 3-phosphate ibuyiselwe kwinqanaba eliqhelekileyo	I-triglyceride neelipidi zizonke azitshintshanga ngenxa yonyango; ukuqokelelana kwamafutha kuhlolo lwezicubu akuzange kutshintshe
Ukutya okunamafutha amaninzi, iimpukwana ze-C57BL/6 eziyindoda, ukutya kangangeeveki ezi-8 kunye nonyango kwiiveki ezi-4 zokugqibela	Imethylene blue eyi-3 okanye i-10 mg nge-kg ngosuku ngomlomo, kane ngeveki	Umlinganiselo we-NAD+ ne-NADH unyukile kwiiseli nasesibindini seempukwana; i-SIRT1 inyukile, i-AMPK ivuselelwe, ukuncitshiswa kokubonakaliswa kwe-SIRT1 kuthintele impembelelo kwi-AMPK	Amafutha aboniswa nge-Oil Red O anciphile, i-triglyceride iphantsi, ukudumba kweeseli kuncinci, i-ALT iphantsi
Iimpuku ze-Wistar ezizimazi ezisempilweni, kungekho nto ibangela isifo, iintsuku ezingama-30	Imethylene blue eyi-1 mM emanzini okusela	I-SOD, icatalase, neglutathione azitshintshanga; i-peroxidation yeelipidi inyukile esibindini, yehla ezintsweni	Akukho siphumo silinganiswe ngesibindi esinamafutha; i-ALT necreatinine kwiserum ziphantsi, i-BUN ayitshintshanga

Itheyibhile yenza ingongoma ephambili ibonakale. Idayi ezuba efanayo, ibhayoloji eyahlukileyo. Isifundo seethanol sahlula impumelelo ye-redox ekusileleni ukunciphisa amafutha. Isifundo sokutya sidibanisa ukuhanjiswa kwemiqondiso nokuncipha kwamafutha kwimodeli enye. Isifundo sezilwanyana ezisempilweni sibonisa ukuba iziphawuli ze-redox zinokutshintsha ziye kumacala achaseneyo ngokuxhomekeke kwilungu lomzimba.

Kutheni kungekho bango lonyango lilandelayo

Akukho nasinye kwezi zifundo esabandakanya abantu abanesibindi esinamafutha. Iidosi, iindlela zokunikezela, namaxesha zahlukile phakathi kwamaphepha, kwaye azinakuguqulwa zibe yinkqubo yonyango ebantwini ngokuhlengahlengisa izixa kuphela. Amaqela amancinci, ingakumbi izilwanyana ezintathu ngexesha ngalinye lomlinganiselo we-redox kuphando lweethanol nezintlanu kwiqela ngalinye kuphando lwezilwanyana ezisempilweni, ashiya ukungaqiniseki okukhulu. Isini, umnombo wezilwanyana, ukwakheka kokutya, nexesha lokuqalisa unyango xa kuthelekiswa nokwenzakala zonke zahlukile. Iimodeli ezimbini zesifo zikwamele oonobangela bokuqala abahlukileyo, ngoko isiphumo esihle sokutya asikwazi ukulungisa isiphumo esibi seethanol, okanye ngokuchaseneyo.

Kuye nabani na ofunyaniswe enesifo sesibindi, eyona nto ingxamisekileyo efanele ifundwe yeyokulumka, kungekhona eyonyango. Isishwankathelo sezilumkiso ngezintso nesibindi malunga nemethylene blue sichaza ukuba kutheni ukungasebenzi kakuhle kwamalungu kutshintsha imibuzo yokhuseleko nokuba iphepha lophando lwezilwanyana libonakala lineziphumo ezintle. Yisa kwingcali yezonyango ingxelo yoxilongo, iziphumo zamva nje zovavanyo lwaselabhoratri, imveliso kanye nendlela yokuyisebenzisa, kunye noluhlu olupheleleyo lwamayeza, uze ubuze ukuba bubuphi ubungqina obuxhasa loo mveliso kuloo njongo kumntu onelo nqanaba lokungasebenzi kakuhle kwamalungu.

Isishwankathelo: imethylene blue yatshintsha imeko ye-redox esibindini kwimodeli enye yeethanol ngaphandle kokunciphisa amafutha agciniweyo, yavuselela i-SIRT1 ne-AMPK ngoxa inciphisa amafutha kwimodeli enye yemetabolism kwiimpukwana, yaza yabonisa iimpembelelo ze-redox ezahlukileyo ngokwelungu lomzimba kwiimpuku ezisempilweni. Le yingqokelela yezikhokelo zophando, hayi unyango oluqinisekisiweyo lwesibindi esinamafutha.