Inqaku
Imethylene blue nokudumba: oko kulinganiswa bubungqina
Imethylene blue inokunciphisa imiqondiso ethile yokudumba phantsi kweemeko zovavanyo. Oko akuyiqinisekisi njengonyango jikelele lokudumba ebantwini. Izifundo eziphononongwa apha zixhasa ukuba inefuthe kwiinkqubo zebhayoloji, zibonisa iinzuzo ezithile kwizilwanyana kunye neziphumo ezimbalwa, ezikhethekileyo kakhulu, ebantwini. Aziqinisekisi ukuba ukuthatha imethylene blue kuphucula iimpawu zemihla ngemihla ekuthiwa zibangelwa “kukudumba okungapheliyo.”
Umbuzo oluncedo ucace ngakumbi: yeyiphi inkqubo yokudumba etshintshileyo, kweyiphi imodeli, kwaye ngaba olo tshintsho luphucule isiphumo esibalulekileyo kwisigulana? Uxinzelelo lwecytokine, ukumila kweseli, kunye nobude bexesha lonyango kwigumbi labagula kakhulu ziphendula imibuzo eyahlukeneyo. Uphononongo lwethu olubanzi lweenzuzo zemethylene blue kuphando lwabantu lubeka ezi ziphumo ecaleni kwezinye iindlela ezicetywayo zokuyisebenzisa kwezempilo.
Yintoni ebalwa njengesiphumo sokunciphisa ukudumba?
Ukudumba kulungelelanisa iimpendulo kusulelo nasekwenzakaleni. Kunokuba negalelo kumonakalo, kodwa ezinye iinkqubo zokudumba zikwaxhasa ukukhuselwa nokulungiswa komzimba. Ngoko ke, “ukudumba okuncinci” yinkcazelo engaphelelanga ngaphandle kokuchaza indawo, into ekubangelayo, ixesha, kunye nesiphumo.
Icytokine yiproteni ethumela imiqondiso. Abaphandi banokulinganisa ubungakanani bayo obufumaneka kulwelo ekukhuliselwa kulo iiseli okanye egazini. Endaweni yoko, banokulinganisa ukuveliswa kwe-enzyme yokudumba, imeko yokusebenza kweproteni ethumela imiqondiso, okanye utshintsho kwimilo yeseli yamajoni omzimba. Le milinganiselo inokubonisa ifuthe lechiza ngaphandle kokubonisa ukuba intlungu, ukudinwa, ukusebenza kwengqondo, okanye ukusebenza kwesifo kuyaphucuka.
Ilipopolysaccharide, edla ngokufinyezwa ngokuthi LPS, yinxalenye yebhaktheriya esetyenziselwa ukuvusa impendulo yokudumba. Izifundo ezininzi zemethylene blue zisebenzisa le nto ivusa impendulo phantsi kweemeko ezilawulwayo. Ukuvusa impendulo nge-LPS kuluncedo ekuvavanyeni indlela esebenza ngayo inkqubo, kodwa akuphindi kuvelise zonke iimpawu zesifo esingapheliyo ebantwini. Lo mda ukwasebenza xa ichiza linikwa ngaxeshanye nento evusa impendulo: ukuthintela utshintsho olubangelwe luvavanyo kwahlukile ekubuyiseleni umva isifo esele sikhona.
Itheyibhile yobungqina: imodeli, into evusa impendulo, isiphumo esilinganisiweyo, ukubaluleka
Le theyibhile ishwankathela izifundo zophando lokuqala ezikhethiweyo. Umqolo ngamnye ugcina umahluko phakathi koko abaphandi bakulinganisileyo noko umfundi anokuthemba ukuba kuthethwa sisiphumo.
| Isifundo kunye nemodeli | Into evusa ukudumba okanye imeko | Isiphumo esilinganisiweyo kunye noko kufunyenweyo | Ukubaluleka kunyango lwezigulana |
|---|---|---|---|
| UHuang noogxa bakhe, 2015: iimacrophage zeempuku kunye neempuku | I-LPS kunye/okanye ne-interferon-gamma kwiiseli ezikhuliswe elebhu; i-endotoxemia kwiimpuku | Ukuveliswa okuncitshisiweyo kwe-inducible nitric oxide synthase, okanye i-iNOS | Kuxhasa ifuthe kwi-enzyme yokudumba; akulinganisi iimpawu ebantwini |
| UAhn noogxa bakhe, 2017: iimacrophage kunye neeseli zabantu ze-THP-1 | Ukuvuselelwa kweeinflammasome ezininzi kuvavanyo | Ukukhutshwa okuncitshisiweyo kwe-IL-1β kunye nokusebenza okunxulumene neeinflammasome | Ubungqina bendlela esebenza ngayo inkqubo; umgca weeseli zabantu awulolingelo kwizigulana |
| UAhn noogxa bakhe, 2017: iimpuku | Ukuvusa impendulo nge-LPS; uvavanyo olwahlukileyo lokuvusa impendulo ngeListeria | Ukusinda okuphuculweyo emva kwe-LPS kunye ne-IL-1β encinci kumngxuma wesisu phantsi kweemeko zovavanyo | Kubandakanya isiphumo kwizilwanyana esingaphaya komlinganiselo webhayoloji; akubonisi ukusinda okuphuculweyo ebantwini |
| ULi noYing, 2023: iimpuku | Izitofu ze-LPS eziphindaphindiweyo kwiintsuku ezintathu | I-IL-6 encinci kwiserum, ukuvuselelwa okuncinci kwe-STAT3 engqondweni naseluswini, kunye nokuncipha okuncinci kobunzima | Kubonisa utshintsho kwimiqondiso kunye nempendulo yesilwanyana siphela; akukho mlinganiselo weempawu ebantwini okanye wokuthomalala kwesifo |
| UAburel noogxa bakhe: iisampulu zezicubu zamafutha anxulumene nentliziyo nemithambo yegazi ebantwini | Izicubu eziqokelelwe ngexesha lotyando kwizigulana ezingama-25 ezinokusilela kwentliziyo; ukugcinwa phantsi kweemeko zaselebhu, kuquka ukuvusa impendulo ngeserotonin | Ukuveliswa okuncinci kwe-monoamine oxidase kunye nemilinganiselo ephantsi yoxinzelelo lwe-oxidative | Kunokubaluleka kwizicubu zabantu, kodwa uxinzelelo lwe-oxidative alufani nokudumba, kwaye izigulana azizange zinyangwe kolu vavanyo |
| UStelmashook noogxa bakhe, 2026: iiseli zeglia ezikhuliswe elebhu ezivela kwicortex yengqondo yeempuku ezinkulu | Ukuchanabeka kwi-LPS kangangeeyure ezingama-24 | Xa kukho imethylene blue, iimicroglia zazinezandiso ezininzi kunye nemizimba yeeseli emincinci kunaxa kukho i-LPS kuphela | Isiphumo esimayela nemilo, ngaphandle kobungqina bokuphucuka kwenkumbulo, ukuziphatha, okanye iimpawu ebantwini |
| UMemis noogxa bakhe, 2002: izigulana ezingama-30 ezinesepsis enzima | Ukufakwa echizeni ngomthambo kangangeeyure ezintandathu kuthelekiswa nesisombululo setyuwa kulingelo olwabiwa ngokungakhethiyo | Akukho futhe libalulekileyo kumanqanaba eecytokine alinganisiweyo kwiplasma | Uvavanyo oluthe ngqo ebantwini aluzange luqinisekise ukuncitshiswa kweecytokine phantsi kwaloo nkqubo |
| UIbarra-Estrada noogxa bakhe, 2023: izigulana ezingama-91 ezinomothuko obangelwa yisepsis ezihlalutywe kuphando | Imethylene blue efakwa ngomthambo ithelekiswa neplacebo, yongezwa kunyango kwigumbi labagula kakhulu | Ixesha elifutshane lokusetyenziswa kweevasopressor; iicytokine azizange zilinganiswe | Isiphumo esithile kunyango lwezigulana, indlela esenzeka ngayo engazange iqinisekiswe ngovavanyo lweempawu zokudumba |
Umahluko ontathu oguqula indlela yokutolika
Imiqondiso encinci ayithethi ngokuzenzekelayo ukusebenza okungcono
Isifundo se-iNOS sango-2015 saphanda indlela imethylene blue eyanciphisa ngayo ukuveliswa kwe-enzyme ebandakanyekayo kwiinkqubo zebhayoloji zenitric oxide. Oku kunceda ukuchaza ifuthe elinokubakho lechiza. Akuqinisekisi ukuba ukunciphisa loo enzyme kunganceda wonke umntu onesifo esinxulumene nokudumba.
Ngokufanayo, isifundo seempuku sango-2023 sanxulumanisa utshintsho kwi-IL-6 esegazini notshintsho kwimiqondiso yezicubu. Isiphumo saso sokuncipha kobunzima songeza inkcazelo eluncedo malunga nesilwanyana siphela. Nangona kunjalo, ubunzima ngexesha lokuvuswa kwempendulo ebukhali abufani nokusebenza kwengqondo, umgangatho wobomi, okanye ukulawulwa okuqhubekayo kwesifo esingapheliyo. Inkcazelo eneenkcukacha ngakumbi yeeinflammasome, i-IL-6, kunye ne-STAT3 icacisa iindlela ezisebenza ngayo ezi nkqubo ngaphandle kokuzibeka endaweni yeziphumo zempilo.
Inkangeleko yeseli ngumlinganiselo omnye
Iimicroglia ziiseli zamajoni omzimba ezikwinkqubo yemithambo-luvo esembindini. Izandiso zazo ezinamasebe kunye nemizimba yeeseli zinokutshintsha ngokwemeko ezikuyo. Kwisifundo seeseli ezikhuliswe elebhu sango-2026, imethylene blue yaguqula inkangeleko yeeseli ezichanabeke kwi-LPS ukuba isondele kwinkangeleko yeqela lolawulo.
Umfanekiso weqweqwe ubonisa olu thelekiso ngomzobo ocacisayo. Ayingomfanekiso othathwe ngemikroskopu okanye ukuveliswa ngokutsha kovavanyo ngokwemilinganiselo yalo. Amasebe amaninzi awangqineli ngokwawo ukuba iseli ikhusela iineuron, isusa ngokufanelekileyo iintsholongwane ezibangela izifo, okanye iphucula ukusebenza kwengqondo. Loo mabango afuna imilinganiselo eyongezelelweyo. Uphononongo lweemicroglia, iiastrocyte, kunye nokudumba luphonononga loo meko ngokweenkcukacha ngakumbi.
Izicubu zabantu azingomntu ofumene unyango
Isifundo samafutha anxulumene nentliziyo nemithambo yegazi sasebenzisa iisampulu ezivela ebantwini, nto leyo esenza sibaluleke kwibhayoloji yabantu. Abaphandi bachanaba ezo sampulu kwimethylene blue ngaphandle komzimba kangangeeyure ezingama-24. Le ndlela inokubonisa impendulo kwizicubu ezithathiweyo, kodwa idlula ukufunxwa, ukusasazwa emzimbeni, imetabolism, kunye nokusebenzisana kwamalungu omzimba.
Saphinda salinganisa uxinzelelo lwe-oxidative kunye nokuveliswa kwe-monoamine oxidase. Ezo nkqubo zinokusebenzisana nokudumba, kodwa ukuncipha kweentlobo zeoksijini ezisebenza ngokukhawuleza akubobungqina ngokwako bokuncipha kwesifo esinxulumene nokudumba. Lo mahluko ubalulekile ekufundeni uphando lweeseli, lwezilwanyana, lwezicubu, kunye nolwezigulana.
Oko kuboniswa zizifundo zezigulana noko zingakubonisi
Isepsis inika uvavanyo oluthe ngqo lwengcinga yokuba imethylene blue imele inciphise iicytokine zokudumba ebantwini. Ulingelo oluncinci olwabiwa ngokungakhethiyo kwizigulana ezinesepsis enzima aluzange lufumane ifuthe elibalulekileyo kwiicytokine. Oko akungqineli ukuba akukho futhe linokwenzeka ngayo nayiphi na inkqubo yonyango okanye imeko. Kodwa kubonisa ukuba kutheni iziphumo ezilungileyo kwiiseli zingenakuthathwa njengeziphumo ezisebenza kubo bonke abantu.
Kulingelo lomothuko obangelwa yisepsis lwango-2023, ixesha eliphakathi de kuyekwe iivasopressor laliyi-69 yeeyure xa kusetyenziswa imethylene blue kunye ne-94 yeeyure xa kusetyenziswa iplacebo. La mayeza axhasa uxinzelelo lwegazi. Izinga lokusweleka alizange lahluke ngokubalulekileyo, kwaye isifundo sasisincinci kakhulu ukuba singawuqinisekisa umba weso siphumo. Ababhali baxela ngokucacileyo ukuba abazange balinganise iicytokine ukuqinisekisa indlela elenzeka ngayo ifuthe. Ngoko ke, inzuzo ekujikelezeni kwegazi kunyango lwabagula kakhulu ayinakuqinisekisa unyango lokudumba ngokubanzi, okanye ithethelele ukusetyenziswa kwaloo nkqubo yonyango ekhaya.
Yintoni enokuxhasa ibango elibanzi lezempilo?
Ibango eliqinisekisayo lifuna iqela lezigulana elichazwe ngokucacileyo, into efanelekileyo yokuthelekisa, ulungiselelo lwechiza kunye nendlela yokulisebenzisa ezinokuphindwa ngokufanayo, kunye nesiphumo esifana neempawu, ukusebenza komzimba, ukusebenza kwesifo, okanye iingxaki ezibangelwa sisifo. Ixesha lokulandelela limele libe lide ngokwaneleyo ukuze kuvavanywe inzuzo ecetywayo kunye neengozi zayo. Umlinganiselo webhayoloji olungileyo unokuxhasa obo bungqina; awunakubuthatha indawo.
Amabango malunga ne-MCAS kunye nokunganyamezeli ihistamine afuna ubungqina bawo obujolise kwezo zifo. Izifundo zeecytokine ngokubanzi azinakuqinisekisa ukuba imethylene blue ilawula iimpawu ezinxulumene neeseli zemast.
Kukwakho neengozi ezisebenzayo zokucinga ukuba ifuthe elibonwe kuvavanyo lunyango olukhuselekileyo. Inkcazelo yangoku yase-US yokumisela iProvayBlue efakwa ngomthambo idwelisa imethemoglobinemia efunyenweyo njengemeko esetyenziselwa ukuyinyanga, ilumkisa ngeserotonin syndrome enzima xa isetyenziswa namachiza achaphazela iserotonin kunye neeopioid, kwaye iyakwalela ukusetyenziswa xa kukho ukunqongophala kwe-G6PD ngenxa yomngcipheko we-anemia ebangelwa kukuqhekeka kweeseli ezibomvu zegazi. Ingcinga yokuba inokunciphisa ukudumba ayiwasusi la mafuthe echiza.
Kubafundi abahlola ibango ngemveliso, celani isifundo sezigulana esixhasa isiphumo esithenjiswayo. Ukuba ubungqina buphelela kwicytokine, kwisampulu yezicubu, okanye kwifoto yeseli, inzuzo ebangwayo kunyango lwezigulana ihlala ingaqinisekiswanga.