Indlela yokufunda uphando nge-methylene blue: isikhokelo seentlobo zezifundo

Qwalasela iziphumo ezimbini ezipapashiweyo. Kwesinye, idosi enye ye-methylene blue ethathwe ngomlomo yonyusa umsebenzi wobuchopho ngexesha lemisebenzi yokunikela ingqalelo neyenkumbulo yaza yaphucula ukubuyiswa kwenkumbulo nge-7 percent. Kwesinye, i-methylene blue yehlisa ukuhamba kwegazi ebuchotsheni kunye nemetabolism yeoksijini yobuchopho kubantu abasempilweni abathathe inxaxheba. Yimolekyuli enye, kodwa iziphumo zisingise kumacala achaseneyo. Umfundi othatha zombini njengezigqibo zombuzo omnye uya kugqiba kwelokuba enye yazo imele ukuba ayichananga.

Akukho nanye engachananga. Zabuza imibuzo eyahlukileyo, kwiinkqubo ezahlukileyo, ngeedosi ezahlukileyo, ngeendlela ezahlukileyo zokufakwa, zaza zalinganisa iziphumo ezahlukileyo ngamaxesha ahlukeneyo. Eli nqaku likufundisa ukubona loo mahluko ngendlela umphandi awubona ngayo, ukuze ibango elilandelayo odibana nalo lihlelwe ngaphambi kokuba likholelwe. Imvelaphi yento eyenziwa yimolekyuli kwinqanaba leekhemikhali ichazwe kwisichazi sendlela esebenza ngayo, kwaye umbuzo wokuba idosi iyitshintsha njani impembelelo uchazwe kuhlaziyo lobungqina bedosi. Apha umxholo bubungqina ngokwabo.

Iphepha ngalinye liphendula umbuzo omxinwa

Isiphumo sesifundo asikhe sibe yingxelo malunga ne-methylene blue ngokubanzi. Siyingxelo malunga ne-methylene blue kwimodeli ethile, enikwe ngendlela ethile, ngedosi ethile, ithelekiswa nolawulo oluthile, ilinganiswa ngesiphumo esithile, ngexesha elithile. Guqula nokuba yenye yezi zinto kwaye impendulo inokutshintsha. Nazi iindawo ezisixhenxe ekufuneka uzizalise kwiphepha ngalinye olifundayo:

Imodeli. Iiseli kwisitya, impuku, izicubu zabantu ezigcinwe ziphila ngaphandle komzimba, okanye abantu. Inqanaba ngalinye elinyukayo longeza ukufana nemeko yokwenene lize linciphise ulawulo.
Indlela yokufakwa. Iginye, ifakwe emthanjeni, itofwe kwilungu, okanye ifakwe ngepipette kwiiseli. Indlela yokufakwa imisela ukuba ingakanani efikelela kwizicubu nokuba ifika ngokukhawuleza kangakanani.
Iiyunithi zedosi. Milligrams per kilogram kwizilwanyana nakubantu, micromolar kwiiseli nakwiibhafu zezicubu. Ezi yunithi azinakuguqulelwa enye kwenye ngezibalo kuphela, kuba ukufunxwa, ukusasazwa, ukubophelela kwiiproteni, kunye nokususwa emzimbeni kusembindini wazo.
Into ethelekiswa nayo. I-placebo, isisombululo se-vehicle, izilwanyana ezinganyangwanga, okanye inqanaba lokuqala langaphambi kwedosi. Isiphumo esingenanto kuthelekiswa nayo luphawulo, hayi ukufunyaniswa.
Iziphumo ezilinganisiweyo. Yintoni kanye kanye eyalinganiswayo: umqondiso weskeni sobuchopho, inqanaba le-enzyme, ukuxinana kwamathambo, amanqaku ovavanyo. Iimpawu ezimele iziphumo (izinto ezisetyenziswa endaweni yesiphumo) azisosiphumo ngokwaso.
Ixesha. Idosi enye elinganiswa emva kweyure enye libango elahlukileyo ekunikweni kwedosi yonke imihla unyaka wonke.
Ukungaqiniseki. Ubungakanani besampulu, abantu abasempilweni xa kuthelekiswa nezigulana, nokuba ababhali ngokwabo bayayikhankanya imida. Izifundo ezincinci zokuqala zivelisa iingcinga eziza kuvavanywa; azizigqibi.

Imizekelo emine engezantsi izalisa eli phepha lokusebenzela kusetyenziswa amaphepha okwenene, kuquka amabini abonakala ngathi ayaphikisana.

Umzekelo 1: ulingo lwabathathi-nxaxheba olufumene umsebenzi wobuchopho ongaphezulu

Kwi-randomized, double blind, placebo controlled imaging trial, abantu abadala abasempilweni abangama-26 abaneminyaka engama-22 ukuya kuma-62 benza imisebenzi yokugcina ingqalelo ixesha elide kunye neyenkumbulo yexesha elifutshane ngaphakathi kweskena, emva koko baginya nokuba yi-280 mg ye-methylene blue ekumgangatho wamayeza (malunga ne-4 mg/kg) okanye i-placebo yedayi yokutya eluhlaza okwesibhakabhaka, baza baphinda loo misebenzi emva kweyure enye. Iqela ledayi labonisa iimpendulo ezinamandla ngakumbi kwi-insular cortex ngexesha lokunikela ingqalelo nakwiinethiwekhi ze-prefrontal, parietal, kunye ne-occipital ngexesha lenkumbulo, kunye neempendulo ezichanekileyo ezingaphezulu nge-7 percent xa kubuyiswa inkumbulo. Uvavanyo lwe-carbon dioxide alubonise lutshintsho ekuphenduleni kwemithambo yegazi, nto leyo ababhali abayifunda njengobungqina bokuba umqondiso wawubonisa ukusetyenziswa kweoksijini endaweni yeempembelelo kwimithambo yegazi.

Ukufunda ngephepha lokusebenzela: imodeli, abantu abasempilweni. Indlela yokufakwa, ikhapsuli ethatyathwa ngomlomo. Idosi, i-4 mg/kg enye. Into ethelekiswa nayo, i-placebo, kwaye ukufihlwa kolwazi kwakhuselwa ngokucela abathathi-nxaxheba ukuba bangachami phakathi kweseshoni (umchamo oluhlaza okwesibhakabhaka wawunokutyhila ukuba ngubani ofumene unyango). Iziphumo ezilinganisiweyo, umqondiso weskeni kunye namanqaku emisebenzi. Ixesha, iyure enye emva kwedosi enye. Ukungaqiniseki, abantu abangama-26, abasempilweni, iseshoni enye, kunye nesiphumo sokulinganisa ngeskeni endaweni yesiphumo sezonyango.

Into oku kungqina yona imxinwa kodwa iyinyani: idosi enye ephantsi ethathwe ngomlomo yatshintsha umsebenzi wobuchopho onxulumene nemisebenzi kubantu abadala abasempilweni ngaloo mini. Ayivavanyi unyango lwayo nayiphi na imeko, ukusetyenziswa kwexesha elide, okanye nayiphi na enye idosi. Amabango malunga nenkumbulo kunye nokusebenza kwengqondo kufuneka avavanywe kuthathelwa ingqalelo loo mda.

Umzekelo 2: ukungqubana okungelulo

Iqela elalandelayo lalinganisa ukuhamba kwegazi kunye nemetabolism ngokuthe ngqo emva kwe-methylene blue efakwe emthanjeni, kubantu abasempilweni abasibhozo (0.5 kunye ne-1 mg/kg) nakwiimpuku (2 kunye ne-4 mg/kg). Zombini iintlobo zabonisa ukwehla kokuhamba kwegazi ebuchotsheni ngokubanzi; imetabolism yeoksijini ebantwini yehla, yaza nokusetyenziswa kweglucose kwiimpuku kwehla. Ingcaciso yababhali ngokwabo yayikukuziphatha kwedosi: i-methylene blue ineempembelelo ezimbini ezixhomekeke kwidosi, ivuselela xa ukubonakaliswa kuyo kusezantsi ize ithintele xa kuphezulu, uluhlu olusezantsi ludla ngokuchazwa malunga ne-0.5 ukuya kwi-4 mg/kg kwaye impembelelo ijike ngaphezu malunga ne-7 ukuya kwi-10 mg/kg, ngokuxhomekeke kwimodeli.

Beka la maphepha mabini okusebenzela ecaleni kwaye ukungqubana kuyanyamalala. Indlela yokufakwa eyahlukileyo (emthanjeni xa kuthelekiswa nangomlomo), iidosi ezahlukileyo, iziphumo ezilinganisiweyo ezahlukileyo (isantya semetabolism xa kuthelekiswa nomsebenzi ovuswa ngumsebenzi), kunye nexesha elahlukileyo (ukufakwa ngomthambo kwimizuzu engama-30 ngaphambi kweskeni xa kuthelekiswa nekhapsuli iyure enye ngaphambi koko). Idosi efakwe emthanjeni efika ngexesha elinye ayilingani nokubonakaliswa kwikhapsuli efunxwa emathunjini, kwaye isantya semetabolism xa umntu ephumle asilolinganiselo olufanayo nomsebenzi ngexesha lomsebenzi wenkumbulo. Amaphepha abonakala ephikisana adla ngokuba ngamaphepha aphendula imibuzo eyahlukileyo, kwaye ibali lokuphendula kwidosi eliwadibanisayo lichazwe kushwankathelo lwe-hormesis kunye nedosi.

Umzekelo 3: izicubu zabantu ezifundwe ngaphandle komzimba

Isifundo sokuqala safukamisa iisampulu zamafutha ezathathwa ngexesha lotyando lwentliziyo kunye ne-methylene blue. Iisampulu zazivela kwizigulana ezingama-25 ezine-heart failure: i-epicardial kunye ne-perivascular adipose tissue, oko kukuthi iidiphozithi zamafutha ezingqonge intliziyo nemithambo yegazi ezinegalelo kwi-oxidative stress. Emva kokufukanyiswa iiyure ezingama-24 kunye ne-0.1 micromolar ye-methylene blue, izicubu zabonisa ukubonakaliswa okusezantsi kwee-enzyme ze-monoamine oxidase (ubukhulu becala i-MAO-A) kunye ne-reactive oxygen species ezimbalwa. Ukongeza i-serotonin, i-substrate ye-MAO-A, kwaphinda kwanyusa i-oxidative stress, kwaye i-methylene blue yakunciphisa ngokuyinxenye oko kunyuka.

Ezi zizicubu zabantu kwaye le yimpembelelo yebhayoloji yokwenene, kodwa ayilulo ulingo lonyango ebantwini. Akukho mntu wanikwa idosi. Kwakungekho kujikeleza kwegazi, kungekho metabolism yesibindi, kungekho siphumo sezonyango, kwaye i-concentration ekwisitya ngokwayo ayithethi nto malunga nokuba yeyiphi idosi ethathwe ngomlomo ebinokuphinda iyivelise. Umsebenzi we-ex vivo (izicubu ezifundwa ngaphandle komzimba ophilayo) umi phakathi kwenkcubeko yeeseli kunye nophando lwezonyango: ubonisa ukuba impembelelo inokwenzeka kwizicubu zabantu phantsi kweemeko ezilawulwayo, kodwa awunakumisela ukusebenza, ukhuseleko, okanye idosi. Xa ufunda ingxelo malunga neziphumo zezicubu, jonga ukuba isihloko sichaza okwenzeke kwisitya okanye sitsibela kwinto ebiza kwenzeka kwisigulana. Umxholo obanzi wolu hlobo lweziphumo ze-redox ukwisishwankathelo sobungqina be-oxidative stress.

Umzekelo 4: isifundo seempuku apho isiphumo seeseli singazange siqhubeke siphile

Isifundo sokuguga kweempuku savavanya i-methylene blue yexesha elide ngokuchasene nokulahleka kwamathambo okunxulumene nobudala. Iimpuku ezindala ezizimazi zasela amanzi ane-250 micromolar ye-methylene blue iinyanga ezi-6 okanye ezili-12, kwaye iimpuku ezineentlobo ezahlukeneyo zemfuza zanyangwa ukusuka ebudaleni ukuya ekwaluphaleni. Kwinkcubeko yeeseli le khompawundi yayinciphise ukwahluka kwee-osteoclast, uhlobo lwesiphumo oludla ngokuqalisa izihloko ezinkulu. Kwizilwanyana eziphilayo ayitshintshanga nto: ukumila kwethambo le-cortical kunye ne-trabecular kwaguga kanye njengakwiimpuku ezinganyangwanga, kwaye ingalo ehambelanayo ye-MitoQ nayo ayibonisanga siphumo.

Lo ngumahluko wokuguqulela iziphumo ukusuka kwinkqubo enye ukuya kwenye ngendlela ecacileyo. Isitya sigcina i-concentration ingatshintshi, sisusa zonke iinkqubo zamalungu omzimba, size silinganise indlela enye yokuziphatha kweseli. Isilwanyana songeza amathumbu, isibindi, izintso, iihomoni, kunye neenyanga zokuzilungelelanisa komzimba. Isiphumo esingenamahluko esifana nesi asikokungaphumeleli kwenzululwazi; yinzululwazi esebenzayo, ekhupha ingcinga yokuvavanywa (unyango lwe-antioxidant lodwa lukhusela ithambo eligugayo) ngaphambi kokuba nabani na ayiphinde ebantwini. Iziphumo zezilwanyana zixhasa okanye zenze buthathaka indlela ecetywayo yokusebenza. Azimiseli ukusetyenziswa ebantwini, umda obalulekileyo nanini na amabango ngobomi obude nokuguga ecaphula idatha yeempuku.

Iphepha lokusebenzela, lilungele ukukotshwa

Kwiphepha okanye kwinqaku elilandelayo malunga nephepha, zalisa oku ngaphambi kokugqiba ukuba ucinga ntoni:

Imodeli: iiseli, isilwanyana (loluphi uhlobo, sisempilweni okanye siyagula), izicubu zabantu ze-ex vivo, abantu abasempilweni abathathe inxaxheba, okanye izigulana?
Indlela yokufakwa: ngomlomo, emthanjeni, inaliti yendawo ethile, okanye ifakwe ngqo kwiiseli okanye kwizicubu?
Iiyunithi zedosi: mg/kg (umzimba) okanye micromolar (isitya)? Ungaze uguqule enye iye kwenye ngobunzima bemolekyuli kuphela.
Into ethelekiswa nayo: i-placebo, i-vehicle, iqela elinganyangwanga, okanye inqanaba lokuqala langaphambi kwedosi? Ngaba ukufihlwa kolwazi kwakhuselwa?
Iziphumo ezilinganisiweyo: zilinganiswe ngokuthe ngqo okanye zizinto ezimele iziphumo? Umqondiso weskeni, inqanaba le-enzyme, kunye nesiphumo sesifo zinamandla amathathu ahlukeneyo ebango.
Ixesha: idosi enye okanye ukusetyenziswa ixesha elide? Kulinganiswe emva kwemizuzu, iiyure, okanye iinyanga?
Ukungaqiniseki: bangaphi abathathi-nxaxheba, kwaye ababhali ngokwabo bathi yintoni eyayinomda? Izifundo zokuqala, zabantu abasempilweni abathathe inxaxheba, kunye nezifundo zedosi enye zivelisa iingcinga eziza kuvavanywa.

Imikhwa emibini yenza eli phepha lokusebenzela likhawuleze. Okokuqala, funda iindlela phambi kwesigqibo; isigqibo sikuxelela oko ababhali bakukholelwayo, kodwa iindlela zikuxelela oko ubungqina babo bubavumela ukuba bakukholelwe. Okwesibini, xa izifundo ezimbini zingavumelani, thelekisa amaphepha okusebenzela ngaphambi kokuthelekisa izigqibo. Umahluko kwimodeli, kwindlela yokufakwa, kwidosi, nakwiziphumo ezilinganisiweyo usombulula uninzi lwezinto ezibonakala ngathi ziyaphikisana ngaphandle kokuba kubekho nabani na ongachananga. :::