I-methylene blue nokwelashwa ngokukhanya okubomvu: ubufakazi be-PBM uma kuqhathaniswa ne-PDT

Abafundi ababili babhala i-methylene blue nokwelashwa ngokukhanya okubomvu ebhokisini lokusesha, kodwa basho izinto eziphikisanayo. Omunye ucabanga ngephaneli ebomvu esiza ama-mitochondria asebenze kangcono, kufakwe nodayi oluhlaza okwesibhakabhaka ukuze kwandiswe umphumela. Omunye ucabanga ngenqubo yokwelapha isikhumba lapho ukukhanya kushukumisa udayi ukuze ubhubhise okuthile okungafuneki. Bobabili basebenzisa amagama afanayo. Bachaza imiqondo ehlukene, futhi lokhu kudideka kubalulekile ngoba ukukhanya okuhlanganiswe nodayi kungathumela isignali engqamuzaneni noma kulilimaze.

Lo mehluko uyisihloko salokhu kubuyekezwa. I-photobiomodulation, evame ukubizwa nge-PBM, isebenzisa ukukhanya okubomvu noma okusondelene ne-infrared ukuze kulungiswe ukuthunyelwa kwamasignali avela ngaphakathi emzimbeni, ngaphandle kokwengeza isishukumisi esizwelayo ekukhanyeni. Ukwelashwa kwe-photodynamic, okuvame ukubizwa nge-PDT, kusebenzisa izingxenye ezintathu ndawonye: ukukhanya okunobude begagasi obumuncwa isishukumisi, isishukumisi esizwelayo ekukhanyeni njenge-methylene blue, kanye nomoya-mpilo ukuze kukhiqizwe ngobuningi izinhlobo ezisebenza kakhulu ezilimaza okuhlosiwe. Ezingxoxweni eziku-inthanethi, ukwelashwa ngokukhanya okubomvu nge-methylene blue kubekwa kuzo zombili lezi zinhlobo. Ikhemistri eshukunyiswa ukukhanya iyona enquma ukuthi inhlanganisela ethile ingeyaluphi uhlobo.

Ukumuncwa kunquma ukuthi ukukhanya nodayi kuyasebenzisana yini

I-methylene blue esesimweni se-monomer emanzini imunca kakhulu ukukhanya okubomvu, nenani eliphakeme lokumuncwa eliseduze no-664 kuya ku-665 nm kanye nengxenye eseceleni yejika lokumuncwa ebudeni begagasi obufushane obuseduze no-610 nm, ekhula njengoba ama-molecule kadayi eqoqana. I-molar extinction coefficient eduze nenani eliphakeme lokumuncwa icishe ibe ngu-65,000 kuya ku-85,000 M-1 cm-1, yingakho izixazululo ezisezingeni lama-micromolar ziluhlaza okwesibhakabhaka ngokugqamile. Lokhu akulona nje iphuzu elingenamsebenzi. Kuyisimo esidingekayo ngaphambi kokuba kwenzeke noma yikuphi ukusabela okushukunyiswa ukukhanya ngosizo lwesishukumisi.

Ukumuncwa kubeka udayi esimweni se-singlet esihlala isikhathi esifushane, bese udlulela esimweni se-triplet esihlala isikhathi eside, kanti amanani abikiwe okukhiqizwa kwesimo se-triplet aseduze no-0.5. Esixazululweni esikhishwe umoya-mpilo, leso simo se-triplet sihlala amashumi ama-microsecond. Esixazululweni esinomoya, lesi sikhathi sehla sibe cishe ama-microsecond angu-2 ngoba umoya-mpilo ucisha leso simo esishukunyisiwe. Kulokhu kucishwa yilapho izindlela ezimbili zekhemistri eshukunyiswa ukukhanya zehlukana khona.

Kukhemistri ye-Type II, udayi osesimweni se-triplet udlulisela amandla emoyeni-mpilo osesimweni samandla ayisisekelo bese ukhiqiza umoya-mpilo we-singlet, ngenani lokukhiqizwa elivame ukucashunwa eliseduze no-0.52. Kukhemistri ye-Type I, kunalokho, udayi osesimweni se-triplet udlulisela i-electron noma i-hydrogen entweni esabela nayo, okuholela kuma-radical ahlanganisa izinhlobo ze-superoxide ne-hydroxyl. Zombili lezi zindlela zingasebenza ngesikhathi esisodwa. Ngokuchazwa kwayo, i-Type II idinga umoya-mpilo ongama-molecule, kanti i-PDT evamile, njengomphumela ezintweni eziphilayo, isalokhu incike kakhulu emoyeni-mpilo ngisho nalapho i-Type I nayo inegalelo.

Umphumela osebenzisekayo walokhu ngumthetho wobude begagasi. Ukukhanya okubomvu okusukela cishe ku-630 kuya ku-680 nm kuhambisana kahle nebhande lokumuncwa likadayi, kanti u-660 kuya ku-665 nm useduze nenani eliphakeme lokumuncwa kwe-monomer, ngakho kungashukumisa ikhemistri yesishukumisi esizwelayo ekukhanyeni ezicutshini eziqukethe udayi ngenani elibonakalayo. Ukukhanya okusondelene ne-infrared okungu-810 nm kungaphandle kakhulu kwalelo bhande lokumuncwa lesimo samandla ayisisekelo, ngakho lobu bude begagasi abuyishukumisi kahle ngokuqondile i-methylene blue. Ukuchayeka ku-810 nm kuhlanganiswe ne-methylene blue akufanele kuchazwe njengokushukunyiswa kukadayi ngokukhanya. Kungcono kuchazwe njengezindlela ezimbili ezithinta ama-mitochondria ezisetshenziswa ngesikhathi esisodwa. Lo mehluko ulawula konke okulandelayo, futhi uxoxwa nangasohlangothini lwekhemistri embhalweni oyinkomba wekhemistri ye-methylene blue.

Imiqondo emibili ehlanganyela ama-mitochondria kodwa ehlukene ngendlela esebenza ngayo

Ukubuyekezwa kwama-mitochondria njengento eqondiwe ekuvikeleni amangqamuzana ezinzwa, okucashunwa kabanzi, kubhangqa lezi zindlela ezimbili ngoba zombili zigcina zithinta ukuphefumula kwamangqamuzana nakuba ziqala ezindaweni ezahlukene. Kumodeli evamile ye-PBM, into ehlongozwayo emunca ukukhanya yi-cytochrome c oxidase eku-Complex IV. Umbono oyinhloko uthi ama-photon akhuthaza ukuhlukana kwe-nitric oxide evimbelayo ne-enzyme, okwandisa ukugeleza kwama-electron nokwakhiwa kwe-ATP. Leyo modeli kufanele iqhubeke ibizwa ngombono ongakaqinisekiswa. Ubufakazi obuyibonisa ngokuqondile busalinganiselwe, ngakho ukuqiniseka lapha kufanele kuhlale kunesilinganiso.

I-methylene blue isebenza ngendlela ehlukile ebumnyameni. Ngomthamo ophansi, isebenza njengento ejikeleza phakathi kokunciphisa nokufaka i-oxidation futhi esiza ukusabela, nanjengomunye umthwali wama-electron. Ama-pyridine nucleotide asesimweni esincishisiwe ayinciphisa ibe yi-leucomethylene blue, engadlulisela ama-electron phambili bese iphinde ijikeleze, ngaleyo ndlela isekele ukugeleza okudlula izingxenye ezingasebenzi kahle phakathi kwe-Complex I ne-Complex III kuyilapho inciphisa ukuvuza kwama-electron. Ukumuncwa kwama-photon ngudayi akudlali ndima kule ncazelo. Lena yikhemistri, hhayi ikhemistri eshukunyiswa ukukhanya, futhi lokhu kudluliselwa kuchazwa kabanzi kokuthi i-methylene blue isebenza kanjani njengomdluliseli wama-electron.

I-PDT ibuyisela ingxenye yesithathu. Ukukhanya kushukumisa isishukumisi, isishukumisi sisebenzisana nomoya-mpilo nezinto esisabela nazo, kanti inhloso iwukulimala okubangelwa i-oxidation endaweni ethile. I-PBM isebenzisa ukukhanya okubomvu noma okusondelene ne-infrared ekuchayekeni okungabangeli ukushisa ukuze kuguqulwe indlela amandla asebenza ngayo emangqamuzaneni, ngaphandle kokwengeza ngamabomu isishukumisi esivela ngaphandle ukuze kwakhiwe ukwanda okusheshayo kwezinto ezinobuthi emangqamuzaneni. Isiqubulo esithi i-PDT ikhiqiza izinhlobo zomoya-mpilo ezisebenza kakhulu kanti i-PBM ayizikhiqizi asilona iqiniso. Umehluko wangempela uphakathi kwekhemistri enobuthi emangqamuzaneni eshukunyiswa ukukhanya ngosizo lwesishukumisi, nokuthunyelwa kwamasignali okulungisa ukusebenza kwawo. Umthamo wodwa awukuhlukanisi lokhu. I-PDT elwa namagciwane kubantu isebenzisa i-methylene blue yasebenzisa u-6 kuya ku-18 J nge-cm eyisikwele, okungamanani ahlangana nalawo e-PBM. Ukuba khona kwesishukumisi, ubude begagasi obumuncwayo, isikhathi, indawo, ukutholakala komoya-mpilo nenhloso kunquma uhlobo lokusebenza. Iqoqo eliphelele lezifundo zokwelashwa kwe-photodynamic ligcina lezi zici zibonakala ekusetshenzisweni ngakunye okuhlosiwe.

Lokho okuboniswa ngempela izifundo zamagundane zenhlanganisela engu-810 nm

Amaphepha amabili enhlanganisela acashunwa kakhulu womabili asebenzisa ukukhanya okungu-810 nm ne-methylene blue yomthamo ophansi kumagundane. Anikeza ulwazi ngokuqondile ngoba u-810 nm awumshukumisi kahle ngokuqondile udayi. Ahlola inhlanganisela yezindlela ezihlukene zokusebenza, hhayi i-PDT ye-methylene blue.

Ocwaningweni lokwelapha amagundane kusengaphambili ngaphambi kokuwancisha ubuthongo, amagundane angamaduna angu-60 ohlobo lwe-BALB/c athola i-methylene blue nsuku zonke engu-0.5 mg nge-kg izinsuku eziyishumi, i-laser eshaya ngezikhathi engu-810 nm njalo ngosuku lwesibili, noma kokubili ngaphambi kokuncishwa ubuthongo. Ukuncishwa ubuthongo kwehlisa ukusebenza ezivivinyweni ze-maze emise okwe-T, zokuxhumana namanye amagundane nezebhokisi le-shuttle, futhi kwanciphisa i-GAP-43, i-PSD-95 ne-synaptophysin ku-hippocampus. Ukwelashwa ngakunye kukodwa ngokuyinhloko kwehluleka ezilinganisweni zokuziphatha, kuyilapho ukwelashwa okuhlanganisiwe kusengaphambili kwabonisa umehluko obalulekile ngokwezibalo uma kuqhathaniswa neqembu elincishwe ubuthongo. Lokhu kuwukuvimbela kumodeli yokuncishwa ubuthongo okuphoqiwe, hhayi ukwelapha ukuphazamiseka kokusebenza kubantu.

Ocwaningweni lokucindezeleka okungapheli olwaluhambisana nokwelashwa, amagundane abhekana nokucindezeleka okuncane okungapheli kuyilapho ethola i-PBM engu-810 nm ngo-8 J nge-cm eyisikwele kathathu ngesonto, i-methylene blue nsuku zonke engu-0.5 mg nge-kg, noma kokubili amasonto amane. Eqenjini lenhlanganisela, kwasetshenziswa i-laser kuqala kwase kujovwa udayi emahoreni amabili kamuva, ngokuqondile ukuze kugwenywe ukukhanyisa izicubu ezinomdayi. Womathathu amaqembu aqeda ukushoda kokufunda. Inhlanganisela yayingengcono ngokujwayelekile. Inzuzo eyengeziwe yabonakala ngokuyinhloko ku-cortisol esengxenyeni ewuketshezi yegazi nasezinhlotsheni zomoya-mpilo ezisebenza kakhulu ebuchosheni.

Alikho kulawa maphepha elisungula umthamo womuntu ophuzwa ngomlomo, izilungiselelo zedivayisi yabathengi, isikhathi esiphakathi kokusebenzisa umuthi nokukhanyisa, noma uhlelo lwasekhaya. Elinye liwukwelapha kusengaphambili ukuvikela ekulimaleni okubikezelwayo. Elinye liyelapha ngesikhathi kubangelwa ukucindezeleka. Ukusebenzisa imiphumela yanoma yiliphi kulawa ukusekela ukuthatha udayi ngaphansi kwephaneli ebomvu kweqa zonke izici ezanquma umphumela.

Ubufakazi besikhumba ikakhulukazi bungobe-PDT, hhayi i-PBM ethuthukisiwe

Idatha yesikhumba sabantu lapho kusetshenziswa i-methylene blue kanye nokukhanya ingeyohlangothi lwe-PDT ngokuyinhloko. Izibonelo zihlanganisa isivivinyo sezinduna ezigulini ezingu-15 lapho kwaqhathaniswa izinhlangothi ezimbili zobuso, kusetshenziswa i-nanoemulgel ye-methylene blue egcotshwayo kanye ne-diode laser engu-665 nm; izifundo ezincane ze-hidradenitis ezinokukhanya okunamandla okushaya ngezikhathi okungu-630 nm noma i-LED engu-635 nm kanye ne-methylene blue; isivivinyo sezibazi sango-2025 esabelwa ngokungahleliwe, esiqhathanisa i-PDT enezinaliti ezincane kusetshenziswa udayi ongu-0.1 wamaphesenti uma kuqhathaniswa nongu-1 wamaphesenti; kanye nephrothokholi yango-2026 yezilonda zezinyawo zesifo sikashukela esebenzisa i-laser engu-660 nm kanye nodayi ongu-1 wamaphesenti. Ubude bamagagasi buqoqana lapho udayi umunca khona. Inhloso iwukubhubhisa endaweni ethile noma ukuhlela kabusha izicubu. Ukwakhiwa komkhiqizo kungokokugcotshwa noma kokufakwa ngaphakathi kwendawo elimele, hhayi okokusabalala emzimbeni wonke.

Le ndlela yokubuka ibalulekile kubafundi abanentshisekelo yokunakekelwa kwesikhumba. Udayi womthamo ophansi uwodwa unezincwadi zocwaningo lwama-fibroblast ezihlukile, kanti ukukhanya okubomvu kukodwa kunezincwadi zocwaningo lwezilonda ezihlukile. Kodwa kuze kube sekupheleni kuka-2026, asikho isivivinyo sabantu esibuyekezwe ngontanga esihlola udayi ophuzwa ngomlomo osabalala emzimbeni kanye ne-PBM ebomvu njengendlela eyodwa ehlanganisiwe yokungenelela esikhumbeni noma emandleni okuqonda. Ubufakazi bengxenye ngayinye iyodwa abuwona ubufakazi benhlanganisela.

Kungani ubude begagasi obuhambisanayo bungesiyo iphrothokholi

Umbuzo wokuthi isetshenziswa kanjani i-methylene blue kanye nokwelashwa ngokukhanya okubomvu udinga impendulo ecophelelayo, hhayi iresiphi. Ukumuncwa kukutshela kuphela ukuthi ukusebenzisana kungenzeka. Umphumela uncike nasekugxileni kukadayi, ekwakhiweni komkhiqizo, emandleni okukhanya afika endaweni nasemandleni okukhanya aphelele atholwayo, esikhathini esiphakathi kokusebenzisa umuthi nokukhanyisa, ekutholakaleni komoya-mpilo nasekujuleni. Ku-660 nm, ukwengeza udayi kungaguqula ukuchayeka obekungafana ne-PBM kube yikhemistri eshukunyiswa ukukhanya eqhutshwa yisishukumisi esizwelayo ekukhanyeni. Yingakho imiphumela yamagundane ka-810 nm ingaqinisekisi ukusetshenziswa kwabathengi kuka-630 kuya ku-680 nm lapho udayi ukhona emzimbeni.

Ukuphepha kuqinisa lo mngcele. Udayi otholakala ngencwadi kadokotela unesexwayiso esifakwe ebhokisini ngobuthi be-serotonin lapho usetshenziswa nemithi ethinta i-serotonin kanye namanye ama-opioid. Akuvunyelwe ukuwusebenzisa lapho kunokushoda kwe-glucose-6-phosphate dehydrogenase. Ubuthi obubangelwa ukukhanya buwumphumela ongemuhle owaziwayo kadayi osabalala emzimbeni, ikakhulukazi lapho kukhanyiswa izicubu ngobude begagasi obuseduze nenani lawo eliphakeme lokumuncwa. Ukuphepha kwamehlo kuncike ebudeni begagasi, emandleni okukhanya afika endaweni nasohlotsheni lomthombo. Izibuko zelanga ezivamile azithathi indawo yesivikelo esishiwo njeng esifanele idivayisi. La maphuzu achazwe kabanzi kumhlahlandlela wokuphepha nokusebenzisana neminye imithi, futhi kufanele asingathwe ngochwepheshe bezokwelapha kunokuba abe yizinhlelo zasekhaya.

Chaza umqondo ngaphambi kokubiza idivayisi ngegama. Ukungabi nasishukumisi kanye nenhloso ethinta ukusebenza kwamandla emangqamuzaneni kusho i-PBM. Udayi ogxile ngezinga elinendima, kuhlanganiswe nobude begagasi obumuncwayo, umoya-mpilo nenhloso yokubhubhisa, kusho i-PDT. I-methylene blue kanye no-810 nm ocwaningweni lwamagundane olushicilelwe kuyisimo sesithathu: izindlela ezimbili ezithinta ama-mitochondria ngaphandle kokushukunyiswa ngokuqondile ngokukhanya. Ukuhlukanisa lezi zimo ezintathu kuvimbela iphutha elivame kakhulu lapha: ukucaphuna ukususwa kwezinkinga zesikhumba nge-PDT njengobufakazi bokuthi udayi uthuthukisa i-PBM, noma ukucaphuna ukubuyiselwa kokusebenza kwamagundane ngo-810 nm njengobufakazi bokuthi iphaneli engu-660 nm kanye nodayi kuyiphrothokholi yamandla okuqonda.