Methylene blue nekuungana kwemafuta muchiropa: zvakawanikwa nezvidzidzo zvekuedza

Kuungana kwemafuta muchiropa izita rimwe rinoshandiswa kutsanangura matambudziko akasiyana. Kune mumwe munhu, chinokonzera dambudziko iri kunwa doro rakawanda kwenguva yakareba. Kune mumwe, kuwanda kwezvinovaka muviri zvinopinda mumuviri, kusapindura zvakanaka kune insulin, uye kuendeswa kwemafuta akawandisa kuchiropa. Maikorosikopu inogona kuratidza kungochengetwa kwemafuta muzviitiko zvose zviri zviviri, asi zvinokonzera izvi pakutanga zvakasiyana. Musiyano iwoyo ndiwo unosarudza kuti kuedza kupi nokupi kunogona kuratidza chii.

Zvinyorwa zvezvidzidzo zvemethylene blue nekuungana kwemafuta muchiropa zvishoma, uye pamubvunzo uyu zvose ndezvekutsvakurudza kusati kwasvika pakuedza muvanhu. Zvidzidzo zvitatu zvakaitwa mumakonzo nembeva ndizvo zvinonyanya kutaurwa, uye hazvisi zvose zvinonongedzera kumhedziso imwe chete. Chimwe chidzidzo chekupa ethanol mukudya chakagadzirisa kuchinja kweredox asi mafuta emuchiropa akaramba asina kuchinja. Chimwe chidzidzo chekudya kune mafuta akawanda chakaderedza mafuta emuchiropa pamwe nekuchinja mukutumirana kwemasaini. Chimwe chidzidzo chemhuka dzine utano chakawana migumisiro yakapesana yeperoxidation yemafuta muchiropa nemuitsvo. Kana zvikaverengwa pamwe chete, zvinoratidza kuti sei zvinhu zvitatu zvinoyerwa zvichifanira kuramba zvakaparadzaniswa: kuchinja kweredox, kutanga kushanda kwemasaini, uye kuungana kwemafuta mumanyama.

Zvinhu zvitatu zvinoyerwa zviri nyore kuvhiringidza

Chiyero cheredox chinotsanangura mabatirwo emaerekitironi. Reshiyo yeNAD+ neNADH muchiropa inoratidza kuti mamiriro ari mukati memasero akanyanya kurasikirwa nemaerekitironi kana kuwana maerekitironi. Oxidation yeethanol inoshandura NAD+ kuva NADH, saka kunwa doro kwenguva yakareba kunoderedza reshiyo iyi. Dhayi inogamuchira maerekitironi inogona kuikwidza zvakare. Izvozvo ikemisitiri, kwete humbowo hwekuti mafuta akachengetwa ava mashoma.

Chiyero chemasaini chinotsanangura kudzora mashandiro. SIRT1 ienzyme inodzora mashandiro, inotsamira paNAD+, uye inoshandura mapuroteni ane chekuita nekushanda kwemitochondria nekubatwa kwemafuta. AMPK inoshanda sechinoona kana simba rava shoma, uye kana yatanga kushanda inokurudzira oxidation yezvinopa simba ichidzora kugadzirwa kwemafuta. Kana chinyorwa chikataura kuti methylene blue yaita kuti SIRT1 itange kushanda muchiropa, chinenge chichitaura kuchinja mukudzora mashandiro. Chinenge chisati chataura zvakaitika kumurwere.

Chiyero chekuongorora manyama nemaikorosikopu kana chebiokemisitiri chinotsanangura chiropa pachacho. Mienzaniso yakajairika inosanganisira huwandu hwetriglyceride pa gram yenyama, kudhayiwa kwemafuta asina charge neOil Red O, kuongorora kuzvimba kwemasero nekukuvadzwa uchishandisa hematoxylin neeosin, uye kushanda kweALT muplasma. Iri boka rechitatu chete ndiro rinopindura kuti kuungana kwemafuta muchiropa kwakavandudzika here mumuedzo iwoyo wemethylene blue.

Kuparadzanisa mapoka aya kunodzivirira kukanganisa kwakajairika pakunzwisisa: mugumisiro wakanaka weredox kana wemasaini haurevi kuti mafuta muchiropa adzikira.

Muenzaniso weethanol: redox yakagadziriswa, mafuta haana kuchinja

Humbowo hwakajeka zvikuru hwekusawana kuvandudzika hunobva muchidzidzo chekupa ethanol mukudya kwenguva yakareba mumakonzo echirume eWistar. Mhuka dzakapiwa ethanol sechikamu chekudya kwemvura, ichiwedzerwa kusvikira yava 36 percent yesimba rose, uye mhuka dzekuenzanisa dzakapiwa huwandu hwakaenzana hwekudya dzichiwana glucose pachinzvimbo chesimba raibva kuethanol. Rimwe boka reethanol nerimwe boka rekuenzanisa akapiwawo methylene blue pa130 mg pa liter yekudya, ingangoita 42 mg pa kg pazuva, kubva pazuva 5 kusvika pazuva 30.

Mamiriro eredox akafungidzirwa pachishandiswa mapeya akajairika ezvinhu zvinobva mumetabolism: lactate nepyruvate pacytosol, uye 3-hydroxybutyrate neacetoacetate pamitochondria. Pakutanga kwekupa ethanol yakawanda mukudya, mapoka eethanol akaratidza kuchinja kukuru, reshiyo yeNAD+ neNADH mucytosol ichidzika neinenge 62 percent uye iya yemitochondria ichidzika neinenge 71 percent, pamwe nekuwanda kweglycerol 3-phosphate. Methylene blue yakadzosera shure kwakawanda kwekuchinja ikoko, ikadzorera glycerol 3-phosphate pedyo nezviyero zvemapoka ekuenzanisa, pasina kuchinja huwandu hweethanol hwaidyiwa, kuwedzera kweuremu hwemuviri, kana ethanol yaiva muserum.

Mafuta emuchiropa akaratidza chimwe chinhu chakasiyana. Pazuva 12, kuungana kukuru kwemafuta kusati kwaitika, triglyceride yakanga isina kusiyana pakati pemapoka. Pazuva 27, mapoka eethanol akanga aine kuwedzera kukuru kwetriglyceride, pasinei nekuti akapiwa methylene blue here kana kwete. Pazuva 30, mafuta ose akawedzera neinenge 89 percent uye triglyceride neinenge 196 percent mumhuka dzaipiwa ethanol mukudya, zvakare pasina kuchinjwa nedhayi. Kuungana kwemafuta pedyo nepakati pemalobule echiropa kwaitaridzika zvakafanana, paine kana pasina kurapwa. Vanyori vakagumisa kuti kuchinja kweredox kunokonzerwa neethanol hakusi iko kunonyanya kukonzera kuungana kwemafuta muchiropa mushure mekupiwa chikafu ichi kwenguva yakareba mumuenzaniso uyu. Kudzidza kusiyanisa kuti zvakawanikwa mumhuka nemumasero zvinoshanda sei pakunzwisisa njodzi kuvanhu kunobatsira pano: mashandiro acho anogona kuva echokwadi asi asingadzori mugumisiro.

Ichi ndicho chidzidzo chokutaura kana mumwe munhu achiti kugadziriswa kupi nokupi kweredox kunofanira kubvisa mafuta emuchiropa. Muchirongwa ichi chekuedza, hazvina kuitika.

Muenzaniso wemetabolism: masaini pamwe nemafuta mashoma, mumbeva

Mufananidzo wakasiyana unobva muchidzidzo chemasero echiropa nembeva dzakapiwa chikafu chine mafuta akawanda chakanangana neSIRT1 neAMPK. Mumasero eHepG2, masero eAML-12, uye masero echiropa akatorwa zvakananga mumakonzo, methylene blue yakakwidza reshiyo yeNAD+ neNADH, ikawedzera puroteni yeSIRT1, ikaderedza kubatanidzwa kwemapoka eacetyl pamudzori PGC-1alpha, ikawedzera huwandu hweDNA yemitochondria nekushandiswa kweoxygen, uye ikaita kuti AMPK itange kushanda, zvichiteverwa nekuwedzera kweCPT-1 nePPARalpha. Pakaderedzwa SIRT1, kutanga kushanda kweAMPK kwakanyangarika, izvo zvinobatanidza nhevedzano iyi neSIRT1 muhurongwa ihwohwo hwemasero. Dhayi yakapikisawo masaini ekugadzirwa kwemafuta aibva kune chinokurudzira LXR, T0901317, uye pakuiswa kwepalmitate, kusanganisira kukurudzirwa kweSREBP-1c, FAS, neACC.

Chikamu chemhuka chakashandisa mbeva dzechirume dzeC57BL/6 dzakapiwa chikafu chine 60 percent yemafuta kwemavhiki 8, methylene blue ichipiwa nomumuromo kanokwana kana pavhiki mumavhiki 4 ekupedzisira, pa3 kana 10 mg pa kg pazuva. Mbeva dzakapiwa mushonga dzakaratidza kudhayiwa kushoma neOil Red O, triglyceride shoma muchiropa, kuzvimba kushoma kwemasero nekushatiswa kushoma nemafuta pakuongororwa kwemanyama nemaikorosikopu, uye ALT shoma muplasma pane mbeva dzechikafu chine mafuta akawanda dzisina kupiwa mushonga. Ongororo yekufamba kwemushonga mumuviri yakanga iri muchinyorwa chimwe chete yakawana kuti chikamu chaisvika mukutenderera kweropa mushure mekupiwa nomumuromo chaiva pedyo ne31 kusvika 35 percent, kuchitorwa nemuura kunenge kwakazara asi chikamu chakakura chichishandurwa nemetabolism. Reshiyo yakakwirira zvikuru pakati pehuwandu hwaiva munyama nehwaiva muplasma yakawanikwa muchiropa, izvo zvinoita kuti mugumisiro muchiropa uve unobvira kana tichitarisa kugoverwa kwawo mumuviri.

Icho chiratidzo chaicho chekuderedzwa kwekuungana kwemafuta, asi panogumira humbowo hwacho pakamanikana. Muedzo mupfupi wembeva une mhuka 9 kusvika 10 paboka, chikafu chimwe chete, mwero miviri yemushonga, uye mavhiki mana ekupiwa mushonga. Unoedza kuungana kwemafuta kunobva mumetabolism nezviratidzo zvekuungana kwemafuta pamwe nekuzvimba kwechiropa, kwete chirwere chine chekuita nedoro, uye hauedzi cirrhosis, kudzoserwa shure kwefibrosis, kana mugumisiro upi noupi muvanhu. Basa rezviyero zvemitochondria neredox pakududzira migumisiro yakadaro nderekuiratidza sehumbowo hunotsigira pfungwa ichiri kuedzwa, kwete semwero wemushonga kana nzira yekuushandisa.

Mufananidzo wemanyama ane utano: mwero mumwe chete, nhengo dzakapindura zvakasiyana

Chidzidzo chechitatu chinowanzoshandiswa kutsigira zvinotaurwa nezvechiropa pazvisina kufanira. Mumuedzo wemazuva 30 mumakonzo echikadzi eWistar ane utano, mhuka shanu dzakapiwa 1 mM yemethylene blue mumvura yekunwa uye shanu dzakashandiswa sekuenzanisa. Superoxide dismutase, catalase, neglutathione iri muchimiro chakagamuchira maerekitironi hazvina kuchinja muchiropa kana muitsvo. Peroxidation yemafuta yakakwira zvishoma muchiropa uye yakadzika muitsvo. ALT necreatinine zvemuserum zvakadzika, pasina kuchinja kwenitrogen yeurea muropa.

Dudziro yakatendeseka ndeyekuti mhinduro dzakasiyana zvichienderana nenyama yomuviri mumhuka dzine utano, kwete kurapwa kwechirwere. Kupiwa chinhu chimwe chete kwakaratidzika sekukurudzira oxidation zvishoma maererano nechiratidzo chimwe muchiropa, uye sekudzivirira zvishoma maererano nechiratidzo chimwe chete muitsvo, ukuwo nzira dzakajairika dzekudzivirira oxidation dzakaramba dzisina kuchinja. Nemhuka shanu paboka uye pasina muenzaniso wechirwere, chinyorwa ichi chinoyambira kuti methylene blue haifaniri kunzi chinhu chinodzivirira oxidation muchiropa chero mumamiriro api zvawo. Chinoratidzawo kuti sei kuchinja kwemaenzyme echiropa kuchida mamiriro echirwere akanyatsotsanangurwa kusati kwanzi kunoreva kuvandudzika.

Kuenzanisa kwemiedzo mitatu yechiropa

Tafura inoita kuti pfungwa huru ioneke. Dhayi yebhuruu yakafanana, asi mashandiro emuviri akasiyana. Chidzidzo cheethanol chinoparadzanisa kubudirira pakugadzirisa redox nekukundikana pakuderedza mafuta. Chidzidzo chekudya chinobatanidza masaini nekuvandudzika kwemafuta mumuenzaniso mumwe chete. Chidzidzo chemhuka dzine utano chinoratidza kuti zviratidzo zveredox zvinogona kuchinja zvakananga kumativi akapesana zvichienderana nenhengo.

Nei izvi zvisingatsigiri kutaura kuti kurapa

Hapana chimwe chezvidzidzo izvi chakabatanidza vanhu vane mafuta akaungana muchiropa. Mwero, nzira dzekupa, nenguva dzekupa zvinosiyana pakati pezvinyorwa uye hazvigoni kushandurwa kuita chirongwa chemunhu nokungochinja zviyero zvichienderana nekukura kwemuviri. Mapoka madiki, kunyanya mhuka nhatu panguva imwe neimwe yekuyera redox muchidzidzo cheethanol uye shanu paboka muchidzidzo chemhuka dzine utano, anosiya kusava nechokwadi kwakakura. Kuva hono kana hadzi, rudzi rwemhuka, zvinoumba chikafu, uye nguva yekupa mushonga zvichienzaniswa nekukuvadzwa zvose zvinosiyana. Uye mienzaniso miviri yechirwere inomiririra zvinokonzera zvakasiyana pakutanga, saka mugumisiro wakanaka wechikafu haugoni kugadzirisa mugumisiro usina kunaka weethanol, kana kuti zvakasiyana.

Kune munhu upi noupi akaonekwa aine chirwere chechiropa, zvakanyanya kukosha kuverenga nezvokungwarira pane nezvokurapa. Pfupiso yezvinofanira kungwarirwa pakushandisa methylene blue kana paine dambudziko reitsvo kana rechiropa inotsanangura kuti sei kusashanda zvakanaka kwenhengo kuchichinja mibvunzo yekuchengeteka, kunyange chinyorwa chemhuka chichitaridzika kuva nemigumisiro yakanaka. Enda kuna chiremba neruzivo rwechirwere chakaonekwa, zvabuda mukuongororwa kwerabhoritari kuchangobva kuitwa, chigadzirwa chaicho nenzira yekuchishandisa, uye runyorwa rwakazara rwemishonga. Bvunza kuti humbowo hupi hunotsigira chigadzirwa ichocho nokuda kwechinangwa ichocho mumunhu ane kusashanda zvakanaka kwenhengo kwakadaro.

Muchidimbu: methylene blue yakachinja mamiriro eredox muchiropa mumuenzaniso mumwe weethanol pasina kuderedza mafuta akachengetwa, yakaita kuti SIRT1 neAMPK zvitange kushanda ichideredza mafuta mumuenzaniso mumwe wemetabolism wembeva, uye yakaratidza migumisiro yeredox yakasiyana zvichienderana nenhengo mumakonzo ane utano. Izvozvo zvinopa nzira dzokutevera mukutsvakurudza, kwete kurapa kwakasimbiswa kwekuungana kwemafuta muchiropa.