Indlela yokufunda ucwaningo lwe-methylene blue: umhlahlandlela wezinhlobo zocwaningo

Cabanga ngemiphumela emibili eshicilelwe. Kowokuqala, umthamo owodwa we-methylene blue ophuzwayo wandisa umsebenzi wobuchopho ngesikhathi semisebenzi yokunaka neyenkumbulo futhi wathuthukisa ukubuyiswa kwenkumbulo ngamaphesenti angu-7. Kowesibili, i-methylene blue yehlisa ukugeleza kwegazi ebuchosheni kanye nokusetshenziswa komoya-mpilo ebuchosheni kubavolontiya abanempilo. I-molecule efanayo, izinkomba eziphambene. Umfundi ophatha yomibili njengempendulo yokugcina embuzweni ofanayo uzophetha ngokuthi omunye wemiphumela kumele ube nephutha.

Awukho onephutha. Lezi zifundo zabuza imibuzo ehlukene, ezinhlelweni ezihlukene, ngemithamo ehlukene, ngezindlela zokunikeza ezihlukene, zalinganisa imiphumela ehlukene ngezikhathi ezihlukene. Lesi sihloko sikufundisa ukubona lowo mehluko ngendlela umcwaningi awubona ngayo, ukuze isimangalo esilandelayo ohlangana naso sikwazi ukuhlukaniswa ngaphambi kokuba sikholwe. Isizinda sokuthi le molecule yenzani ezingeni lamakhemikhali sichazwe encazelweni yendlela esebenza ngayo, kanti umbuzo wokuthi umthamo uwuthinta kanjani umphumela uchazwe ekubuyekezweni kobufakazi bemithamo. Lapha, isihloko siwubufakazi uqobo.

Lonke iphepha liphendula umbuzo omncane oqondile

Umphumela wocwaningo awusoze waba isitatimende nge-methylene blue ngokujwayelekile. Uyisitatimende nge-methylene blue kumodeli ethile, enikezwe ngendlela ethile, ngomthamo othile, iqhathaniswe nokulawula okuthile, yalinganiswa ngomphumela othile, ngesikhathi esithile. Shintsha noma iyiphi yalezi zinto, impendulo ingashintsha. Nazi izikhala eziyisikhombisa okufanele uzigcwalise kulo lonke iphepha olifundayo:

Imodeli. Amaseli esitsheni, igundane, izicubu zomuntu ezigcinwe ziphila ngaphandle komzimba, noma abantu. Isinyathelo ngasinye esisondela kubantu sandisa ukufana nesimo sangempela kodwa sinciphisa ukulawula.
Indlela yokunikeza. Ukugwinya, ukujova emthanjeni, ukujova ejoyintini, noma ukufaka ngophiphe emaselini. Indlela yokunikeza inquma ukuthi kungakanani okufika esicutshini nokuthi kufika ngokushesha kangakanani.
Amayunithi omthamo. Amamiligremu ngekhilogremu ezilwaneni nakubantu, ama-micromolar emaselini nasezicutshini ezifakwe oketshezini. Lawa mayunithi awakwazi ukuguqulelwa kwelinye ngelinye ngezibalo kuphela, ngoba ukumuncwa, ukusatshalaliswa, ukubopha kumaphrotheni, nokususwa emzimbeni kuphakathi kwawo.
Okuqhathaniswa nakho. I-placebo, isixazululo esithwala into, izilwane ezingelashwanga, noma isilinganiso sokuqala sangaphambi komthamo. Umphumela ongenakho okuqhathaniswa nakho uwukubonwa nje, hhayi ukutholakele.
Imiphumela elinganisiwe. Yini empeleni eyalinganiswa: uphawu lweskena sobuchopho, izinga le-enzyme, ukuminyana kwamathambo, noma amaphuzu okuhlolwa. Izinkomba ezimele umphumela (izinto ezisetshenziswa esikhundleni somphumela wangempela) aziwona umphumela uqobo.
Isikhathi. Umthamo owodwa olinganiswa ngemva kwehora elilodwa uyisimangalo esihlukile ekunikezweni komthamo nsuku zonke unyaka wonke.
Ukungaqiniseki. Ubukhulu besampula, abavolontiya abanempilo uma kuqhathaniswa neziguli, nokuthi ababhali ngokwabo bayayiveza yini imikhawulo. Izifundo ezincane zokuqala zakha imibono yokuhlolwa; azizixazululi.

Izibonelo ezine ezingezansi zigcwalisa leli shidi ngamaphepha angempela, kuhlanganise namabili abonakala ephikisana.

Isibonelo 1: isivivinyo sabavolontiya esathola umsebenzi wobuchopho owengeziwe

Esivivinyweni sokuthwebula izithombe esasihleliwe ngokungahleliwe, sifihle ukwelashwa kuzo zombili izinhlangothi, futhi silawulwa nge-placebo, abantu abadala abanempilo abangu-26 abaneminyaka engu-22 kuya ku-62 benza imisebenzi yokunaka okuqhubekayo neyenkumbulo yesikhathi esifushane ngaphakathi kweskena, base begwinya noma u-280 mg we-methylene blue wezinga lemithi (cishe u-4 mg/kg) noma i-placebo yombala wokudla oluhlaza okwesibhakabhaka, bese bephinda le misebenzi ngemva kwehora elilodwa. Iqembu le-methylene blue labonisa izimpendulo ezinamandla ku-insular cortex ngesikhathi sokunaka nasezinhlelweni ze-prefrontal, parietal, ne-occipital ngesikhathi senkumbulo, kanye nezimpendulo ezifanele ezengeziwe ngamaphesenti angu-7 ngesikhathi sokubuyisa inkumbulo. Ukuhlolwa nge-carbon dioxide akubonisisanga ushintsho ekuphenduleni kwemithambo yegazi, ababhali abakuhumusha njengobufakazi bokuthi uphawu lwalubonisa ukusetshenziswa komoya-mpilo kunokuba kube yimiphumela yemithambo yegazi.

Ukufundwa kweshidi: imodeli, abantu abanempilo. Indlela yokunikeza, ikhepsuli ephuzwayo. Umthamo, u-4 mg/kg kanye kuphela. Okuqhathaniswa nakho, i-placebo enokufihla ukwelashwa okuvikelwe ngokucela ababambiqhaza ukuba bangachami phakathi neseshini (umchamo oluhlaza okwesibhakabhaka wawuzodalula ukuthi ubani othole umuthi). Imiphumela elinganisiwe, uphawu lweskena kanye namaphuzu omsebenzi. Isikhathi, ihora elilodwa ngemva komthamo owodwa. Ukungaqiniseki, abantu abangu-26, abanempilo, iseshini eyodwa, nenkomba yokuthwebula izithombe esikhundleni somphumela womtholampilo.

Lokhu okufakazelwa yilesi sifundo kuncane kodwa kungokoqobo: umthamo owodwa ophansi ophuzwayo washintsha umsebenzi wobuchopho ohlobene nomsebenzi kubantu abadala abanempilo ngalolo suku. Asihlolanga ukwelashwa kwanoma yisiphi isimo, ukusetshenziswa kwesikhathi eside, noma omunye umthamo. Izimangalo mayelana nenkumbulo nokusebenza kwengqondo kufanele zihlolwe kucatshangelwa lowo mkhawulo.

Isibonelo 2: ukuphikisana okungekhona ukuphikisana

Iqembu elalandela lalinganisa ukugeleza kwegazi kanye ne-metabolism ngokuqondile ngemva kokunikezwa kwe-methylene blue ngomthambo, kubavolontiya abanempilo abayisishiyagalombili (0.5 no-1 mg/kg) nasemagundaneni (2 no-4 mg/kg). Zombili izinhlobo zabonisa ukugeleza kwegazi ebuchosheni jikelele okwehlile; ukusetshenziswa komoya-mpilo kubantu kwehla futhi ukusetshenziswa kwe-glucose kumagundane kwehla. Incazelo yababhali ngokwabo yayiwukuziphatha komthamo: i-methylene blue ine-biphasic response, ivuselela ekuchayekeni okuphansi futhi ivimbele ekuchayekeni okuphezulu, lapho ibanga eliphansi livame ukuchazwa cishe ngo-0.5 kuya ku-4 mg/kg futhi umphumela uguquke ngaphezu cishe kuka-7 kuya ku-10 mg/kg, kuye ngemodeli.

Beka la mashidi amabili eceleni bese ukuphikisana kuyanyamalala. Indlela yokunikeza ehlukile (ngomthambo uma kuqhathaniswa nokuphuza), imithamo ehlukile, imiphumela elinganisiwe ehlukile (izinga le-metabolism uma kuqhathaniswa nomsebenzi ovuswe umsebenzi othile), nesikhathi esihlukile (ukufakwa ngomthambo imizuzu engu-30 ngaphambi kokuskenwa uma kuqhathaniswa nekhepsuli ihora elilodwa ngaphambi kwalokho). Umthamo ongaphakathi emthanjeni ofika wonke ngesikhathi esisodwa awufani nokuchayeka kwekhepsuli emuncwa emathunjini, futhi izinga le-metabolism ngesikhathi sokuphumula aliyona into efanayo nomsebenzi ngesikhathi somsebenzi wenkumbulo. Amaphepha abonakala ephikisana avame ukuba ngamaphepha aphendula imibuzo ehlukene nje, futhi indaba ye-dose response ewaxhumanisayo ichazwe kabanzi ekubukezweni kwe-hormesis nemithamo.

Isibonelo 3: izicubu zomuntu ezifundwe ngaphandle komzimba

Ucwaningo lokuqala lwafaka amasampula amafutha athathwe ngesikhathi sokuhlinzwa kwenhliziyo ku-methylene blue. Amasampula avela ezigulini ezingama-25 ezinokwehluleka kwenhliziyo: izicubu zamafutha e-epicardial nezizungeze imithambo, okuyizinqwaba zamafutha ezizungeze inhliziyo nemithambo ezinomthelela ku-oxidative stress. Ngemva kokufakwa amahora angu-24 ne-0.1 micromolar methylene blue, izicubu zabonisa ukuvezwa okuphansi kwama-enzyme e-monoamine oxidase (ikakhulukazi i-MAO-A) kanye nama-reactive oxygen species ambalwa. Ukwengeza i-serotonin, i-substrate ye-MAO-A, kwaphinde kwandisa i-oxidative stress, futhi i-methylene blue yawunciphisa ngokwengxenye lowo mzamo wokwanda.

Lezi yizicubu zomuntu futhi kube nomphumela wangempela wezinto eziphilayo, kodwa akusona isivivinyo sokwelashwa kubantu. Akekho umuntu owanikwa umthamo. Kwakungekho ukujikeleza kwegazi, kwakungekho metabolism eyenziwa yisibindi, kwakungekho mphumela womtholampilo, futhi i-concentration esitsheni ayisho lutho iyodwa mayelana nokuthi yimuphi umthamo ophuzwayo ongayiphinda. Umsebenzi we-ex vivo (izicubu ezifundwa ngaphandle komzimba ophilayo) uphakathi kokucwaninga amaseli nocwaningo lomtholampilo: ukhombisa ukuthi umphumela ungenzeka ezintweni zomuntu ngaphansi kwezimo ezilawulwayo, kodwa awukwazi ukusungula efficacy, safety, noma dosing. Lapho ufunda umbiko ngemiphumela yezicubu, hlola ukuthi isihloko sichaza okwenzeke esitsheni yini noma sidlulela ngokushesha kokuthi bekuzokwenzekani esigulini. Umongo obanzi walolu hlobo lokutholakala kwe-redox usekubuyekezweni kobufakazi be-oxidative stress.

Isibonelo 4: ucwaningo lwamagundane lapho umphumela wamaseli ungazange uphile

Ucwaningo lokuguga kwamagundane lwavivinya i-methylene blue yesikhathi eside ngokumelene nokulahleka kwamathambo okuhlobene nokuguga. Amagundane amadala esifazane aphuza amanzi aqukethe i-250 micromolar methylene blue izinyanga ezingu-6 noma ezingu-12, kanti amagundane ahlukahlukene ngokofuzo alashwa kusukela ebudaleni kuya ekugugeni. Emaselini akhuliswa esitsheni, le nhlanganisela yayinciphise ukuhlukaniseka kwama-osteoclast, uhlobo lomphumela oluvame ukuqala izihloko ezinkulu. Ezilwaneni eziphilayo ayishintshanga lutho: ukuma kwamathambo e-cortical nawe-trabecular kwaguga ngendlela efanayo ncamashi neyamagundane angalashwanga, futhi ingxenye ehambisanayo ye-MitoQ nayo yehluleka ngendlela efanayo.

Leli yigebe lokudlulisa imiphumela kusukela elabhorethri iye ezintweni eziphilayo ngendlela elicace kakhulu. Isitsha sigcina i-concentration ingashintshi, sisuse zonke izinhlelo zezitho zomzimba, futhi silinganise ukuziphatha okukodwa kweseli. Isilwane sengeza amathumbu, isibindi, izinso, amahomoni, nezinyanga zokuzivumelanisa komzimba. Umphumela ongabonisi ushintsho njengalona awukona ukwehluleka kwesayensi; yisayensi esebenza kahle, ichitha i-hypothesis (ukwelashwa nge-antioxidant kuphela kuvikela amathambo agugayo) ngaphambi kokuba umuntu ayiphinde kubantu. Imiphumela yezilwane isekela noma yenza indlela ecatshangelwayo ibe buthaka. Ayinikezi imiyalelo yokusetshenziswa kubantu, umngcele obalulekile noma nini lapho izimangalo zokuphila isikhathi eside nokuguga zicaphuna idatha yamagundane.

Ishidi, selilungele ukukopishwa

Ephepheni elilandelayo noma esihlokweni esikhuluma ngephepha, gcwalisa lokhu ngaphambi kokunquma ukuthi ucabangani:

Imodeli: amaseli, isilwane (uhlobo luni, siphilile noma sigula), izicubu zomuntu ze-ex vivo, abavolontiya abanempilo, noma iziguli?
Indlela yokunikeza: ngomlomo, ngomthambo, ngomjovo wendawo, noma kufakwe ngokuqondile emaselini noma ezicutshini?
Amayunithi omthamo: mg/kg (umzimba) noma micromolar (isitsha)? Ungalokothi uguqule okukodwa kube okunye ngesisindo se-molecule kuphela.
Okuqhathaniswa nakho: i-placebo, isixazululo esithwalayo, iqembu elingalashwanga, noma isilinganiso sokuqala sangaphambi komthamo? Ingabe ukufihla ukwelashwa kwavikelwa?
Imiphumela elinganisiwe: ilinganiswe ngokuqondile noma iyinkomba emele okunye? Uphawu lweskena, izinga le-enzyme, nomphumela wesifo kungamazinga amathathu ahlukene wamandla esimangalo.
Isikhathi: umthamo owodwa noma okuqhubekayo? Kulinganiswe ngemva kwemizuzu, amahora, noma izinyanga?
Ukungaqiniseki: bangaki ababambiqhaza, futhi ababhali ngokwabo bathi yini eyayinemikhawulo? Izifundo zokuqala, ezabavolontiya abanempilo, nezomthamo owodwa zakha imibono yokuhlolwa.

Imikhuba emibili yenza leli shidi lisheshe. Okokuqala, funda izindlela zocwaningo ngaphambi kwesiphetho; isiphetho sikutshela lokho ababhali abakukholelwayo, izindlela zikutshela lokho ubufakazi babo obubavumela ukuba bakukholelwe. Okwesibili, lapho izifundo ezimbili zingavumelani, qhathanisa amashidi ngaphambi kokuqhathanisa iziphetho. Umehluko wemodeli, indlela yokunikeza, umthamo, nomphumela olinganisiwe uxazulula iningi lokuphikisana okubonakala kukhona ngaphandle kokuthi kube khona onephutha. :::