Methylene blue poyerekeza ndi njira za NAD+: momwe zimagwirira ntchito, umboni, ndi zonena za kuziphatikiza

Methylene blue ndi zowonjezera zomwe zimagulitsidwa kuti zimawonjezera NAD+ zonse zimafotokozedwa pogwiritsa ntchito mawu akuti mitochondria ndi mphamvu za maselo. Koma mafotokozedwe onsewa sakukuuzani zimene chinthucho chimachita kwenikweni.

Njira ziwirizi zimakhudza zinthu zosiyana. Imodzi imayesa kusintha kuchuluka kwa NAD+ m'maselo anu. Inayo imasintha chiyerekezo cha mitundu yake iwiri. Izi si njira ziwiri zofikira kumalo amodzi.

Miyezo iwiri yomwe nthawi zonse imasokonezedwa

NAD+ ndi coenzyme. Imalandira ma electron awiri, monga ayoni wa hydride, ndipo imasanduka NADH. NADH ikapereka ma electron amenewo patsogolo, imasandukanso NAD+. Maselo amagwiritsa ntchito kuzungulira kumeneku nthawi zonse: ndi njira imene mphamvu zotengedwa ku chakudya zimafikira ku mapuloteni amene amapanga ATP.

Popeza NAD+ ndi NADH ndi mitundu iwiri ya molekyulu imodzi, pali miyezo iwiri yosiyana yofunika kutsatira m'selo. Woyamba ndi kuchuluka konse: kuchuluka kwa NAD+ ndi NADH zikaphatikizidwa. Wachiwiri ndi chiyerekezo pakati pawo, chomwe chimafotokoza mmene zinthu zonyamula ma electron zilili zodzaza panthawiyo.

Damu limathandiza kumvetsa kusiyana kumeneku. Madzi onse omwe ali kumbuyo kwa khoma la damu ndi kuchuluka konse. Kugawikana kwa madzi osungidwa kumtunda ndi amene atulutsidwa kutsika ndi chiyerekezo. Mungakweze chiyerekezocho popanda kuwonjezera litre imodzi, potsegula chipata. Imeneyi si fanizo chabe la zimene methylene blue imachita. Ili pafupi ndi kufotokoza zimene zimachitikadi.

Njira yowonjezera zinthu zopangira NAD+

Zowonjezera zomwe zimakhala ndi zinthu zoyambira kupanga NAD+, kuphatikizapo nicotinamide riboside, nicotinamide mononucleotide, ndi nicotinamide, ndi zipangizo zopangira. Maselo amapanga NAD+ kudzera m'njira yogwiritsanso ntchito zinthu zotchedwa salvage pathway, ndipo zinthu zoyambirazi zimalowa m'njirayo. Cholinga chake ndi kuwonjezera kuchuluka konse.

M'nyama, zimenezi zatsimikiziridwa bwino: m'mitundu yambiri ya mayeso, NAD+ m'minofu imachepa chifukwa cha ukalamba ndi matenda a kagayidwe ka zinthu m'thupi, ndipo kupereka zinthu zoyambira kupanga NAD+ nthawi zambiri kumawonjezera kuchuluka kwake. Mwa anthu, zimene zatsimikiziridwa ndi zocheperapo. Mayeso mwa anthu amasonyezadi kuti zinthu zimenezi zimawonjezera milingo ya NAD+ yoyezedwa m'magazi. Zimene sizinasonyeze ndi kusintha kwabwino kosasinthasintha pa zotsatira zachipatala, kutanthauza zinthu zimene munthu angazindikire kapena zimene mayeso anakonzedwa kuti ayeze.

Mawu akuti "Milingo ya NAD+ inakwera" amafotokoza muyeso wa chinachake mkati mwa thupi. Si zotsatira zokhudza mmene munthu anamvera, anasunthira, kapena anachirira.

Zimene methylene blue imachita m'malo mwake

Methylene blue si chinthu choyambira kupanga NAD+. Ndi utoto wa redox, umene wakhala ukugwiritsidwa ntchito m'zamankhwala kwa zaka zoposa zana, ndipo ntchito zake zovomerezeka ndi zocheperapo kuposa zomwe zikufufuzidwa.

Mkati mwa selo, ma enzyme odalira flavin amaisintha mwa kuipatsa ma electron kukhala mtundu wopanda utoto, leucomethylene blue, womwe pambuyo pake umatayanso ma electron. Ma electron amene akanadutsa mu complex I, malo oyamba m'ndandanda wa kupuma kwa maselo m'malo mwake angatulutsidwe mu NADH kudzera mwa methylene blue. NADH imasanduka NAD+.

Chiyerekezo chimakwera. Kuchuluka konse sikuwonjezeka.

Kafukufuku wa makoswe wokhudza mtima wokhala ndi matenda a shuga anayeza zimenezi mwachindunji mu mitochondria zotulutsidwa m'maselo a mtima. Kuwonjezera methylene blue pa milingo ya 6 mpaka 18 micromolar pamene ma asidi a mafuta anali kuchitidwa oxidation kunachepetsa NADH ndi chiyerekezo cha NADH ndi NAD+ malinga ndi kuchuluka komwe kunawonjezedwa. Kuchuluka kwenikweni kwa NAD+ kunasintha pang'ono kwambiri poyerekeza ndi NADH, monga mmene mungayembekezere ndi chinthu chosandutsa mtundu umodzi kukhala winawo m'malo mopanga zambiri za uliwonse.

Kumene ma electron amenewo amapita n'kofunika. Mu mitochondria zotulutsidwa m'maselo a ubongo, methylene blue pa milingo ya 100 nanomolar mpaka 1 micromolar inawonjezera kupanga mphamvu pamene ndandanda ya kupuma kwa maselo inali yoletsedwa. Pa nthawi yomweyo, inawonjezera kupanga hydrogen peroxide komanso kuchepetsa kuchotsedwa kwake, pa mikhalidwe yonse yoyesedwa. Olembawo anafotokoza kuti hydrogen peroxide inachokera pa kupatsidwa kwa ma electron mwachindunji ku oxygen ndi methylene blue yomwe inali italandira ma electron. Ma electron otuluka mu NADH kudzera m'njira imeneyi sasowa. Amafika pa oxygen.

Kafukufuku wina wa minofu ya tendon ya Achilles akufotokoza mfundoyi momveka bwino. Methylene blue inabwezeretsa kulinganizana kwa NAD+/NADH ndi kuwonjezera kupanga ATP m'maselo ovulala a tendon ndi m'makoswe omwe anali ndi vuto la tendon. Pepalalo limalemba kuti kuchuluka konse kwa NAD sikunasonyeze kusintha kwakukulu.

Zimene mayeso a minofu ndi nyama amatsimikizira

Mayeso anayi omwe anachitika pazaka makumi anayi amatsatira lingaliro lomwelo ndipo mobwerezabwereza amasonyeza malire ake.

Pa kupereka mowa kwa makoswe kwa nthawi yaitali, ethanol inachepetsa chiyerekezo cha NAD+/NADH m'cytosol komanso mu mitochondria za chiwindi. Kuwonjezera methylene blue m'chakudya kunalepheretsa kwambiri kusintha kumeneko. Koma sikunachepetse kuchuluka kwa mafuta m'chiwindi komwe ethanol inayambitsa. Kukonza chiyerekezo sikunakonze zotsatira zake. Zotsatira za 1985 zimenezo n'zofunika kuzikumbukira musanavomereze zonena zakuti kusintha kwa redox ndiko kumabweretsa phindu linalake.

Mu maselo a chiwindi ndi mbewa zomwe zinkadya chakudya cha mafuta ambiri, methylene blue inakweza chiyerekezo cha NAD+/NADH, inawonjezera SIRT1, inachepetsa kumangiriridwa kwa magulu a acetyl ku PGC-1alpha, inayambitsa ntchito ya AMPK, ndipo inachepetsa kudzikundikira kwa mafuta m'chiwindi. Pano zotsatira zinasinthadi limodzi ndi chiyerekezo. Pepala lomwelo limasonyeza kuti kuwonjezera kuchuluka sikumawonjezera zotsatira zonse mosalekeza: milligrams zitatu pa kilogram patsiku zinawonjezera DNA ya mitochondria bwino kuposa milligrams khumi, pamene kugwiritsa ntchito oxygen ndi kutumiza zizindikiro kwa AMPK zinakwera pamene kuchuluka kunakwera.

Mu mtima wokhala ndi matenda a shuga, methylene blue yoperekedwa m'madzi akumwa kwa masabata khumi ndi limodzi inachepetsa chiyerekezo cha NADH ndi NAD+ mu mitochondria za mtima ndi kuwonjezera ntchito ya sirtuin 3. Kumangiriridwa kwa magulu a acetyl ku lysine kunachepa m'malo 83 pa mapuloteni 34, makamaka amene amakhudzidwa ndi kunyamula ma asidi a mafuta ndi kuwachita oxidation. Gawo la magazi lotulutsidwa ndi mtima pa kugunda kulikonse linasintha bwino. Koma kupuma kwa maselo kothandizidwa ndi complex I sikunakonzeke. Ndipo mayeso ochotsa ntchito ya jini anasiyanitsa zotsatira ziwiri zomwe n'zosavuta kuzisokoneza: kusintha kwa chiyerekezo kunachitika kwambiri popanda sirtuin 3, pamene kuchotsa magulu a acetyl kunadalira sirtuin 3.

Mu kafukufuku wa tendon, methylene blue inagwiritsidwa ntchito pamene complex I inali yotsekedwa ndi mankhwala a rotenone. Inabwezeretsabe kulinganizana kwa NAD+, koma inalepherabe kuteteza ku kuwonongeka kobwera chifukwa cha oxidation, kuwonongeka kwa matrix, ndi kuchepa kwa maselo amoyo. Kubwezeretsa chiyerekezo sikunali kokwanira kuti minofuyo ichire.

Tsamba losindikizika lokhala ndi maumboni onse limagwiritsa ntchito mizere yomweyi.

Chifukwa chake ma sirtuin amalowetsedwa m'nkhaniyi

Ma sirtuin amachotsa magulu a acetyl ku mapuloteni, ndipo amagwiritsa ntchito NAD+ pochita zimenezi. Ntchito yawo imakhudzidwa ndi kupezeka kwa NAD+, choncho chinthu chilichonse chimene chimasintha kupezeka kwake chimasinthanso ntchito ya ma sirtuin.

Apa ndi pamene malonda ambiri a "methylene blue ya NAD+" amadalira. Ndi pamenenso kulingalira kwake kumasokonekera. Kusintha chiyerekezo kungawonjezere ntchito ya ma sirtuin. Koma zimenezi sizitanthauza kuti chinthucho chimapereka NAD+, komanso sizitanthauza kuti zotsatira zake n'zofanana ndi kutenga chinthu choyambira kupanga NAD+. Kutanthauzira miyezo imeneyi potengera redox kuli ndi misampha yakeyake imene ndi bwino kuiwerenga musanavomereze mafotokozedwe aliwonse mwa awiriwa.

Zimene zayesedwa mwa anthu

Methylene blue yakhala ikugwiritsidwa ntchito kuchipatala kwa zaka zambiri pa mavuto adzidzidzi omwe amayang'aniridwa: methemoglobinemia, kuwonongeka kwa dongosolo la mitsempha kokhudzana ndi ifosfamide, ndi kutsika kwambiri kwa kuthamanga kwa magazi pa opaleshoni. Izi ndi ntchito zenizeni zoyang'aniridwa ndi akatswiri, osati umboni wa kumwa tsiku lililonse kuti munthu azichita bwino.

Kufufuza komwe kunachitika polemba nkhaniyi sikunapeze kafukufuku mwa anthu woyeza zinthu za kagayidwe ka NAD+ atapatsidwa methylene blue anthu athanzi odzipereka. Zotsatira zapamwambazi zimachokera ku mitochondria zotulutsidwa m'maselo, maselo okulitsidwa m'labotale, minofu ya makoswe, ndi minofu ya anthu yochotsedwa m'thupi. Tendon yochotsedwa m'thupi n'kusungidwa yamoyo m'mbale ya labotale ndi sitepe yothandiza kupitirira kugwiritsa ntchito maselo okulitsidwa okha. Koma si munthu.

Kafukufuku wa zinthu zoyambira kupanga NAD+ wachitikadi mwa anthu, ndipo zotsatira zake ndi zochepa. NAD+ m'magazi imakwera. Zotsatira zachipatala zimasiyanasiyana ndipo nthawi zambiri kusintha kwake kumakhala kochepa.

Choncho zonena za kuziphatikiza zimabweretsa funso loyenera koma yankho lake silikhutiritsa: palibe kafukufuku wofalitsidwa, mayeso, kapena lipoti la zochitika zingapo lomwe linapezeka pa nkhaniyi lomwe linayesa methylene blue pamodzi ndi nicotinamide riboside, nicotinamide mononucleotide, kapena NAD+ yoperekedwa kudzera m'mtsempha. Aliyense amene akunena kuti kuphatikizaku kuli ndi umboni, kapena kuti ziwirizi zimalimbikitsana, akungoganizira potengera magulu awiri osiyana a umboni.

Kuganizira kumeneku kungalakwike m'njira zonse ziwiri. Kungakhale ndi chiyembekezo chopitirira malire, ngati kuchuluka konse sikunali chinthu cholepheretsa zinthu pambuyo poti chiyerekezo chabwezeretsedwa. Kungakhalenso kosavuta mopitirira, chifukwa zotsatira za methylene blue zikachulukitsidwa zimafika pamene zimasintha kulowera kwina. Ofufuza ake amafotokoza kuti imakhala ndi hormesis: milingo yochepa imalimbikitsa kulandira ma electron, pamene milingo yapamwamba imapatutsa ma electron kuchoka m'ndandanda wa kupuma kwa maselo ndipo ingalimbikitse oxidation. Kuwonjezera zinthu zina zomwe zingagwiritsidwe ntchito sikumapangitsa kusintha kumeneko kukhala kotetezeka kwambiri.

Palinso nkhawa za kugwirizana ndi mankhwala ena zomwe sizikukhudzana ndi NAD+. Methylene blue imalepheretsa ntchito ya monoamine oxidase A, n'chifukwa chake imakhala ndi chiopsezo chokhudzana ndi serotonin ikagwiritsidwa ntchito limodzi ndi mankhwala ena ochiza kuvutika maganizo; ndemanga ya malipoti a poizoni ku dongosolo lapakati la mitsempha inapeza kuti zochitika 13 mwa 14 zinakwaniritsa mfundo za Hunter zozindikira poizoni wa serotonin. Ingayambitsenso methemoglobinemia ngati munthu walandira kuchuluka kwakukulu. Ngati mumamwa mankhwala olembedwa ndi dokotala, funso la kuziphatikiza lomwe muyenera kufunsa dokotala wanu ndi lokhudza njira zimenezo, osati kulinganizana kwa redox. Kusamala komweko n'kofunikanso pa zinthu zomwe zimaphatikizidwa kawirikawiri: zowonjezera zina zomwe zimatengedwa pamodzi ndi methylene blue zili ndi umboni wawo, womwe makamaka sunayesedwe.

Chifukwa chake chiyero chimasankha mayeso amene mukuchita kwenikweni

Chogulitsa cha methylene blue chimakhala chisakanizo mpaka labotale itatsimikizira zosiyana. Chinthu chosafunika chofunika pano ndi Azure B, phenothiazine yomwe yachotsedwa gulu la methyl ndipo si chinthu chosachita kanthu. Ndi utoto wogwira ntchito pa redox wokhala ndi makhalidwe oyambira ofanana a magetsi ndi mankhwala. Choncho chogulitsa chokhala ndi Azure B yochuluka mokwanira kukhudza zotsatira si mtundu woyera kwambiri kapena wonyansa kwambiri wa njira yomweyi. Ndi chisakanizo china chomwe chikukhudza njira yomweyi, pa chiyerekezo chomwe palibe amene wafotokoza makhalidwe ake.

Mulingo wa USP ndi njira imene wogula amapezera chinthu chofotokozedwa ndi miyezo yeniyeni. Chogulitsa chomwe sichili pa mulingo wa USP n'chotheka kwambiri kukhala utoto wa nsalu, ndipo mitundu ya utoto wa nsalu imakhala ndi zinthu zosafunika zomwe zimapangitsa kuti isakhale yoyenera kumwa, kuphatikizapo zitsulo zolemera ndi zotsalira za zosungunulira.

Kusiyanaku sikuli pakati pa milingo yokha. Ogulitsa ambiri amene amanena kuti zinthu zawo zikugwirizana ndi USP amangoyesa zitsulo zolemera, kenako n'kuonetsa mayeso amodziwo ngati kutsatira zofunikira zonse. Zofunikira zonse zimakhudza kuzindikira chinthucho, chiyero, zinthu zosafunika za organic, zotsalira za zosungunulira, zinthu zosafunika za ma element, zotsalira pambuyo powotcha, malire a tizilombo, ndi ma endotoxin a mabakiteriya. Mayeso a gawo limodzi sangatitsimikizire za zinthu zomwe sanayese, ndipo zinthu zosiyidwazo zikuphatikizapo zinthu zofanana ndi chinthucho ndi zotsalira za zosungunulira.

Blupreme imagula methylene blue kwa wopanga mankhwala ndipo imafalitsa satifiketi ya kusanthula yomwe imakhudza zofunikira zonse, kuti chinthu cha m'botolo chikhale chimene kafukufuku akufotokoza. Ngati mukufuna kuunika nokha malingalirowa musanagule, momwe mungawerengere kafukufuku wa methylene blue imafotokoza zimene mtundu uliwonse wa kafukufuku ungasonyeze ndi zimene sungasonyeze.

Kusiyana komwe kumakhalabe koona pakuwunika mosamalitsa

Kuwonjezera chinthu choyambira kupanga NAD+ kumasintha kuchuluka kwa NAD+ komwe kulipo. Methylene blue imasintha zimene NAD+ yomwe ilipo ikuchita. Yoyamba ndi nkhani ya kuchuluka kwa zinthu zoperekedwa, yachiwiri ndi nkhani ya kayendedwe ka zinthu, ndipo mayeso othandizira imodzi safotokoza zambiri za inayo.

Methylene blue ili ndi kufotokozera kogwirizana kwa momwe imagwirira ntchito, komwe kwatsimikiziridwa mu mitochondria zotulutsidwa m'maselo ndi m'minofu ya nyama, koma ndi malire omveka bwino komanso obwerezedwa: kusintha chiyerekezo sikufanana ndi kukonza minofu. Chimene ikusowa ndi mayeso mwa anthu oyeza mmene imakhudzira NAD+. Chimene magulu onsewa alibe ndi mayeso achindunji a kuzigwiritsa ntchito pamodzi.

Magulu onsewa ayenera kuunikidwa mofanana. Funsani kuti chogulitsacho chimanena kuti chimasintha chiyani, kenako funsani kuti ndi miyezo iti ya chinthucho imene ilipo mwa anthu. Ngati yankho lake ndi kafukufuku wa maselo, khoswe, kapena njira yomveka kuti ingachitike, ndiye kuti ndi umboni umenewo basi. Si umboni wa kugwiritsa ntchito zinthu pamodzi.