Chinyorwa
Methylene Blue neChirwere cheShuga: Tsananguro Yekufambiswa kweGlucose neTsvakurudzo paMhuka
Mubvunzo uri pasi pemashoko ekushambadza anowedzeredza
Mhedziso iyoyo inoita seine musoro, asi yakavakirwa panzira isiri iyo yekufunga nezvenyaya iyi. Inobata zvinhu zvitatu zvakasiyana sokunge chinhu chimwe chete: glucose ichipinda musero rimwe chete mundiro yemurabhoritari, kushandurwa kwezvinhu mukati memitochondrion yemwoyo, uye kudzorwa kweglucose mumuviri wemunhu wese. Chimwe nechimwe chine zviyero zvacho nemiganhu yacho. Chinyorwa chino chinozvipatsanura.
Mhinduro pfupi ndeiyi: methylene blue inomutsa kufambiswa kweglucose murudzi rumwe rwemasero rwakanyatsodzidzwa, uye inoshandura mashandiro emakemikari mumitochondria nezvimwe zviyero zvemwoyo mumakonzo ane chirwere cheshuga. Asi muongororo yemakonzo yakatora nguva yakareba kupfuura dzimwe, haina kushandura glucose pakusadya kana hemoglobin yakabatana neshuga, uye hapana humbowo hwakabudiswa kubva muvanhu hunoratidza kuti methylene blue inopiwa kuti ishande mumuviri wese inovandudza shuga muropa, HbA1c, kana insulin muchirwere cheshuga.
Masero: glucose inopinda nokukurumidza ichishandisa mapuroteni ekufambisa agara ari muganda resero
Vatsvakurudzi vakashandisa masero efibroblast eL929, rudzi rwemasero ane kupinda kweglucose kunotsamira papuroteni rimwe chete rekufambisa, GLUT1. Sezvo paine puroteni rimwe chete rekufambisa, chero shanduko pakupinda kweglucose inofanira kubva papuroteni iroro.
Chikwata pachakaisa masero aya mumethylene blue, kupinda kwechinhu chinoshandiswa kuronda kwakawedzera mukati memaminitsi 10 uye kuchienderana nehuwandu hwakapiwa, kuchisvika panenge pa800 muzana yechiyero chekutanga pa50 micromolar kwemaminitsi 45. Tsanangudzo yemwero wekufamba iyi yakakosha: mwero wepamusoro-soro (Vmax) wakakwira asi simba rekubatana (Km) nehuwandu hwepuroteni reGLUT1 hazvina kuchinja. Magonhi aiva akaenzana pauwandu akapfuudza glucose yakawanda paminiti. Dhayi yakamutsa mapuroteni ekufambisa agara ari muganda resero pane kuwedzera matsva.
Miedzo yekuenzanisa inojekesa mufananidzo uyu. Chimiro chakagamuchira maerekitironi (chisina ruvara) hachina chachakaita. Chinhu chinokonzera oxidation chaiva kunze kwemasero uye chaidzivirira dhayi kupinda chakavhara zvose kuiswa kweruvara nokumutswa kwekufambisa. Zvinovhara nzira dzeAMP kinase nePI kinase hazvina chazvakachinja, izvo zvinopa chikonzero chokufunga kuti nzira mbiri idzodzo dzinozivikanwa dzekutumira zviratidzo hadzisi dzakakonzera izvi.
Pfungwa yekutanga yaiva yekutenderera kweoxidation nereduction: dhayi inotakura maerekitironi, inokonzera kusagadzikana kushoma musero, uye masero ari pasi pekusagadzikana anovhura magonhi eglucose. Ongororo yakatevera yakaedza pfungwa iyoyo. Vatsvakurudzi vakashandisa methyl-beta-cyclodextrin, morekuru rakaumbwa serin'i rinobata methylene blue mukati memubatanidzwa wemamorekuru (association constant inenge 310 M-1). Dhayi yakabatwa haina kuisa ruvara mumasero kana kumutsa kupinda kweglucose, uye kubviswa kwedhayi nekusuka kwainyatsoenderana nekurasika kwemhedzisiro yacho. Mhedziso yavo yakapikisa tsananguro yekutenderera kweoxidation nereduction: kumutswa kungangobva pakudyidzana kwakananga kwedhayi nerimwe puroteni riri munzira yekumutsa GLUT1, kwete pakusagadzikana kunokonzerwa neoxidation kwakawanda musero.
Musimboti wemashandiro aya une muganhu. Methylene blue inogona kumutsa kupinda kweglucose kuburikidza neGLUT1 mumasero eL929 munguva pfupi, uye izvi zvinogona kudzokera sezvazvaiva, kuburikidza nekupinda musero pamwe nekudyidzana nepuroteni. Izvi hazvitauri chinhu nezveinsulin, rwatata, kana shuga muropa remhuka mhenyu. Kuti unzwisise dhayi iyi semutakuri wemaerekitironi, ona mashandiro emethylene blue semutakuri wemaerekitironi. Kuti uwane mitemo yekuverenga ongororo dzemasero, ona maverengero etsvakurudzo yemethylene blue.
Makonzo ane chirwere cheshuga: mwoyo yakachinja, shuga muropa haina kuchinja
Tsvakurudzo pamhuka inoenda pane imwe nyaya: mwoyo une chirwere cheshuga. Ongororo mbiri dzemakonzo dzakashandisa streptozotocin, muchetura unoparadza masero ebeta anogadzira insulin uye unokonzera mamiriro akafanana nechirwere cheshuga cherudzi rwe1. Vaverengi vari kutsvaga nezvemethylene blue nechirwere cheshuga cherudzi rwe2 vanofanira kuona kusawirirana uku kubva pakutanga. Mhuka idzi hadzina chirwere cheshuga cherudzi rwe2.
Muongororo yenguva refu, makonzo echirume erudzi rweLewis akapiwa 10 mg pakg pazuva mumvura yekunwa kwemavhiki 11, pamwe nehuwandu hudiki hweinsulin kudzivirira kuonda kwakanyanya pasina kudzosa glucose pachiyero chakajairika. Mumitochondria yemwoyo, dhayi yakabatsira oxidation yeNADH, yakakwidza NAD+, uye yakawedzera kushanda kweSirtuin 3 deacetylase. Kuongorora mapuroteni kwakawana kuderera kwekubatanidzwa kwemapoka eacetyl panzvimbo 83 pamapuroteni 34 emitochondria anoshanda muoxidation yemafuta, kutenderera kwecitric acid, uye kufambiswa kwemaerekitironi. Oxidation yemafuta ane cheni refu nekushanda kwehydroxyacyl-CoA dehydrogenase zvakaderera, zvichidudzirwa sekurerutsa kutsamira zvakanyanya pamafuta kwemwoyo une chirwere cheshuga. Mavhoriyamu nechikamu cheropa chinobudiswa nemwoyo pakurova zvakavandudzika uye chiratidzo chekukura kwemwoyo chakadzokera pachiyero chakajairika, kunyange zvazvo dzvinyiriro nekumhanya kwekubatana kwemwoyo zvakaramba zvakaderera.
Uyu ndiwo mugumisiro unokosha kupfuura mimwe: shuga muropa haina kuchinja. Glucose pakusadya uye kana pasina kutsanya yakaramba yakakwira, uye HbA1c yakaramba iri pedyo ne5.6 muzana mumakonzo ane chirwere cheshuga akapiwa mushonga neasina kuupiwa zvakafanana, pasina shanduko inokosha yakakonzerwa nemushonga. Dhayi haina zvakare kugadzirisa kukanganisika kwekufema kunobva kucomplex I neII mumitochondria yakanga yaparadzaniswa. Kushanda kwemwoyo kwakavandudzika pane zvimwe zviyero asi kudzorwa kweglucose nekukanganisika kukuru kwekufema hazvina kuvandudzika. Mhedzisiro dzakasiyana dzakaramba dzakasiyana.
Ongororo yechipiri yakatarisa pachikamu chidiki: mitochondria yakaparadzaniswa kubva mumwoyo ine utano nemwoyo yaiva nechirwere cheshuga kwemwedzi miviri, ichipiwa kamwe chete huwandu hudiki hwe0.1 micromolar panguva yekuyera. Kushandiswa kweoxygen kwakakwira nezvinhu zvinoshandiswa necomplex I neII zvakafanana. Asi kubudiswa kwehydrogen peroxide kwakasiyana zvichienderana nechinhu chaishandiswa sesimba: kwakakwira neglutamate pamwe nemalate, kukaderera nesuccinate. Kubatwa kwecalcium hakuna kuchinja. Uku kuongorora mashandiro emushonga pamitochondria, kwete muedzo wekushanda kwemwoyo kana weglucose. Chidzidzo chacho ndechekuti dhayi iyi haisi antioxidant inoshanda zvakafanana mumamiriro ose. Kukwira kana kuderera kwekubudiswa kwezvinhu zvinokonzera oxidation kunotsamira pachinhu chinoshandiswa nemitochondrion sesimba. Kuti uwane imwe tsananguro inoenderana neiyi, ona methylene blue mutsvakurudzo yemwoyo netsinga dzeropa.
Tafura yemamodheru nezviyero zvemhedzisiro: zvakaedzwa, zvakachinja, uye zvisina kuchinja
| Modheru | Zvakaitwa nemethylene blue | Chiyero chemhedzisiro chakayerwa | Mugumisiro |
|---|---|---|---|
| Masero efibroblast eL929, GLUT1 chete, kupinda kwechinhu chekuronda | Kumutswa nokukurumidza kwemapuroteni ekufambisa agara aripo, Vmax yakakwira, Km haina kuchinja, hapana puroteni idzva reGLUT1 | Mwero wekupinda kweglucose mundiro yemurabhoritari | Wakawedzera kusvika pakupetwa ~8 pa50 micromolar, ukadzokera sezvawaiva mushure mekubviswa nekusuka |
| Masero efibroblast eL929 pamwe necyclodextrin inobata dhayi | Dhayi yakavharirwa kunze kwemasero, kuiswa kweruvara kwakamira | Kumutswa kwekupinda kweglucose | Kwakavharwa pamwe chete nekuiswa kweruvara, zvichitsigira kudyidzana kwakananga nepuroteni pane kusagadzikana kwakawanda kunobva kuoxidation nereduction |
| Makonzo ane chirwere cheshuga chakakonzerwa neSTZ, 10 mg/kg/day nemuromo, mavhiki 11 | Oxidation yeNADH, NAD+ yakakwira, kushanda kweSirtuin 3 kwakakwira, mapoka eacetyl akabviswa panzvimbo 83 dzemitochondria, oxidation yemafuta ane cheni refu yakaderera | Mavhoriyamu emwoyo, chikamu cheropa chinobudiswa pakurova, chiratidzo chekukura kwemwoyo | Zvimwe zvakavandudzika (mavhoriyamu, chikamu cheropa chinobudiswa pakurova, ANP yakadzokera pachiyero chakajairika; dzvinyiriro nedP/dt zvakaramba zvakaderera) |
| Ongororo imwe chete yemakonzo yenguva refu | Kupiwa huwandu humwe chete | Glucose pakusadya, glucose kana pasina kutsanya, HbA1c | Hapana shanduko inokosha; chirwere cheshuga chakaramba chiripo |
| Ongororo imwe chete yemakonzo yenguva refu, mitochondria yakaparadzaniswa | Kupiwa nemuromo kwenguva refu, kwoteverwa nekuyera kufema kunze kwemuviri | Oxidative phosphorylation inotsigirwa necomplex I neII | Kukanganisika hakuna kugadziriswa |
| Mitochondria yakaparadzaniswa yemwoyo ine utano neine chirwere cheshuga, 0.1 micromolar kwenguva pfupi | Kuchinjwa kwenzira dzemaerekitironi panguva yekuyera kufema | Kushandiswa kweoxygen | Kwakawedzera nezvinhu zvinoshandiswa necomplex I neII |
| Ongororo imwe chete yemitochondria yenguva pfupi | Kupiwa huwandu humwe chete | Kubudiswa kwehydrogen peroxide | Kwakatsamira pachinhu chaishandiswa: kwakakwira neglutamate/malate, kukaderera nesuccinate |
| Vanhu, kupiwa kuti ishande mumuviri wese | Hapana muedzo wakabudiswa une shuga muropa sechiyero chikuru chemhedzisiro uye une mhedzisiro yakaiswa pachena | HbA1c, glucose pakusadya, insulin | Hapana kuvandudzika kwakabudiswa kwakawanikwa |
Vanhu: humbowo pamusoro peshuga muropa muvanhu hushoma zvikuru
Muedzo unogona kuongorora maronda muvanhu vane chirwere cheshuga usingaongorori kudzorwa kweglucose, uye kurapwa kwemazino kunogona kutaurawo HbA1c sechiyero chekuwedzera pasina kuedza kurapa chirwere cheshuga.
Mumwe muedzo wakanyoreswa, NCT05850611, unoronga methylene blue inopiwa nemuromo (70 mg mumukaka, mavhiki mana) yemaronda etsoka ane chekuita nechirwere cheshuga, glucose pakusadya, insulin, uye HbA1c zviri pakati pezviyero, asi hauna kuisa mhedzisiro pachena. Ongororo diki yekutanga yakabudiswa yakabatanidza jeli replasma rine maplatelet akawanda nehuwandu hudiki hwedhayi inopiwa nemuromo pamaronda etsoka, ikataura mhedzisiro yemaronda nekupiwa kweoxygen, kwete yeshuga muropa. Miedzo yekurapwa kwemazino yakaisa dhayi panzvimbo chaiyo sechinhu chinomutswa nechiedza kuti chirwise utachiona muvarwere vane periodontitis nechirwere cheshuga haina kuwana kubatsira kwakakosha paHbA1c. Dhayi inoiswa muhomwe yenyama dzemazino inyaya yakasiyana nemushonga unoshandura mashandiro ezvinhu mumuviri wese, saka kushaikwa kwemhedzisiro mumiedzo iyoyo hakutauri chinhu pamusoro pekupiwa nemuromo zvakare.
Pfupiso yakatendeseka ndeiyi: hapana humbowo hwakabudiswa kubva muvanhu hunoratidza kuti methylene blue inopiwa kuti ishande mumuviri wese inovandudza HbA1c, glucose pakusadya, kana insulin muchirwere cheshuga. Kushaikwa kwehumbowo hakusi humbowo hwekuti hapana mhedzisiro, asi hakutsigiri kushambadza kunopa kupinda kweglucose mumasero kana zvakawanikwa mumwoyo yemakonzo sehumbowo hwekudzorwa kweglucose. Kuti uzive miganhu yekuchengeteka munhu asati aedza, kusanganisira njodzi yeserotonin syndrome nemishonga yakajairika yekurapa kuora mwoyo, ona kuchengeteka kwemethylene blue nekudyidzana kwayo nemimwe mishonga.
Mashandisiro ehumbowo uhwu usingazvinyengeri
Funga nezvemichina mitatu. Muchina wekutanga igonhi reglucose musero rimwe chete rakakuriswa murabhoritari. Muchina wechipiri imitochondrion mumwoyo wegonzo. Muchina wechitatu munhu ane chirwere cheshuga, ane rwatata, chiropa, mhasuru, itsvo, mishonga, uye chikafu. Zvakaratidzwa kuti dhayi ine zvainoita pamuchina wekutanga newechipiri. Hazvina kuratidzwa kuti muchina wechitatu unopindura nekudzora glucose zviri nani.
Musiyano iwoyo ndiwo musoro wechinyorwa ichi mundima imwe chete. Mashoko pamusoro pemethylene blue mukutarisirwa kwechirwere cheshuga anonongedzera pakumutswa kwemapuroteni ekufambisa kana pakubatanidzwa kwemapoka eacetyl mumitochondria pane chiyero cheshuga muropa anenge achinja nyaya. Zvakawanikwa pamusoro peSirtuin 3 neoxidation yemafuta zvichiri kukosha kuti zvirambe zvichitariswa, asi muedzo unofanira kutarisirwa wakajeka: muedzo une boka rekuenzanisa muvanhu vane chirwere cheshuga unoyera HbA1c, glucose pakusadya, kana insulin sechiyero chikuru chemhedzisiro.