Methylene blue kuri MS: gusobanukirwa ubushakashatsi bwa EAE ku nyamaswa

Iyo ushakishije methylene blue kuri MS, ubona inyandiko z'ubushakashatsi zisa n'izisubiza ikibazo kimwe. Nyamara si ko biri. Imwe yahaye imbeba zirwaye methylene blue mu rwego rwo kuzivura. Indi ntiyigeze iyikoresha mu kuvura inyamaswa n'imwe. Yakoresheje methylene blue nk'irangi ry'ubururu ku duce duto dukase tw'uruti rw'umugongo, kugira ngo inzobere mu gusuzuma impinduka z'indwara mu ngirabuzimafatizo ibashe kubona myelin ikoresheje mikorosikopi.

Iri tandukaniro ni ryo shingiro ry'iyi ngingo yose. Iri rangi rifite imirimo ibiri mu binyabuzima, kandi nta cyo iyo mirimo ihuriyeho uretse icupa rivamo. Iyo rigeragezwa nk'umuti, rihabwa inyamaswa nzima, hakabazwa niba indwara ihinduka. Iyo rikoreshwa nk'irangi, rishyirwa ku ngirabuzimafatizo zapfuye kandi zabungabunzwe nyuma y'igerageza, hakabazwa uko izo ngirabuzimafatizo zari zimeze. Iyo utabonye iryo tandukaniro, ushobora gusoma igice gisobanura uburyo bwo gusuzuma impinduka z'indwara nk'aho kivuga ibyavuye mu kuvura.

EAE ni iki, mu magambo yoroshye

Experimental autoimmune encephalomyelitis, ikunze kwitwa EAE mu mpine, ni uburyo busanzwe bukoreshwa ku nyamaswa kugira ngo bigane bimwe mu biranga multiple sclerosis. Umushakashatsi atera imbeba ishobora kwandura urushinge rurimo igice cya poroteyine ya myelin hamwe n'ikinyabutabire gikomeye cyongera igisubizo cy'ubudahangarwa. Hanyuma ubudahangarwa butangira kwibasira urwungano rw'imyakura rw'iyo nyamaswa rugizwe n'ubwonko n'uruti rw'umugongo. Imbeba igira intege nke zigenda zizamuka mu mubiri, kandi byoroshye kuzipima ku gipimo cya 0 kugeza kuri 5, kuva ku murizo utakigagara kugeza ku bumuga bw'amaguru y'inyuma.

Kuba byoroshye gutanga ayo manota bisobanura impamvu EAE ikoreshwa cyane, ariko nanone bisobanura impamvu ishobora kuyobya. MS yo mu bantu yizana ubwayo, ikibasira ibintu byinshi kandi bitasobanuwe neza, igatera ibimenyetso bifata kureba, kumva ibyiyumvo, ubushobozi bwo gutekereza, imikorere y'agace k'ubwonko gahuza ingendo, no kugenda; ishobora kugaruka mu bihe bitandukanye cyangwa kugenda ikomera. EAE yigana uburyo bumwe na bumwe, nko kubyimbirwa, gutakaza myelin no kwangirika kwa axone, mu miterere igenzurwa. Ntabwo ari MS yiganywe mu buryo buto. Abasomyi bashaka gusobanukirwa ishusho rusange bashobora kubanza gusuzuma uko methylene blue itekerezwa gukora ku rwego rw'uturemangingo mbere yo guca urubanza ku cyemezo icyo ari cyo cyose kijyanye n'indwara runaka.

Inyandiko ebyiri zikurikira zanakoresheje antigene zitandukanye mu gutera EAE, kandi ibyo ni ingenzi. Ubushakashatsi bwo kuvura bwateye indwara bukoresheje MOG35-55, peptidi ngufi ikomoka kuri glycoprotein ya myelin ikorwa n'uturemangingo twa oligodendrocyte. Ubushakashatsi bw'impinduka z'indwara bwateye indwara bukoresheje MP4, ihuza ibice bya poroteyine shingiro ya myelin n'ibya poroteyine ya proteolipid. Guhitamo ubwoko bw'imbeba na antigene bihindura aho ibice byangiritse bigaragara n'uko kubyimbirwa kugenda. Bityo, ubu bushakashatsi bubiri si igerageza rimwe ryakozwe kabiri.

Incamake: icyitegererezo, ikibazo n'imbibi

Jya uguma kureba iyi mbonerahamwe. Ni yo mfashanyigisho y'ibanze y'iyi ngingo. Buri murongo werekana ikibazo cyo kwa muganga icyo cyitegererezo gishobora gusubiza, ibyapimwe koko, n'aho guhuza ibyavuye ku nyamaswa n'abantu bigarukira.

	Ubushakashatsi bwo kuvura (MOG EAE)	Ubushakashatsi bw'impinduka z'indwara (MP4 EAE)
Inyandiko	Ubushakashatsi bwo kuvura EAE yatewe na peptidi ya MOG	Ubushakashatsi bukurikirana impinduka z'indwara zatewe na MP4 mu gihe
Uruhare rwa methylene blue	Ikintu cyageragejwe ku mbeba nzima	Irangi ryashyizwe ku duce tw'uruti rw'umugongo twabungabunzwe, dufite umubyimba wa 1 micrometer
Ikibazo cyo kwa muganga bushobora gusubiza	Ese gutanga umuti bihindura ubukana bwa EAE n'ubutumwa bw'ubudahangarwa	Gutakaza myelin no kwangirika kwa axone bigenda bite mu gihe cy'amezi atandatu
Ibipimo by'ibisubizo	Amanota y'ibimenyetso bya buri munsi, uturemangingo twinjiye mu ruti rw'umugongo, gutakaza myelin, kwangirika kwa axone, ubutumwa bwa AMPK na SIRT1, imikorere ya NF-kB, uburinganire bwa Th17 na Treg	Ubuso bw'ibice byangiritse, amanota yo kubyimbirwa no kubika amazi, ubucucike bw'imitsi yatakaje myelin, g-ratio ipimwe na mikorosikopi ya elegitoroni, gusenyuka kwa axone, kubyimba kwa mitochondria, intera hagati ya neurofilaments
Imbibi zo guhuza ibisubizo n'abantu	Ubwoko bumwe bw'imbeba, igitsina kimwe, igihe kigufi cy'iminsi 30, isano aho kuba gihamya y'uburyo bibaho	Nta buvuzi bwageragejwe, gufata ingirabuzimafatizo mu matsinda atandukanye ku bihe bitandukanye, ibice byangiritse byafashwe ahanini mu gice cy'uruti rw'umugongo cyo mu rukenyerero

Umuntu wese usuzuma umutwe w'inkuru ikurikira ashobora kongera gukoresha izi nkingi afashijwe n'uko wasoma ubushakashatsi bubanziriza igerageza ku bantu: abaze ubwoko bw'inyamaswa na antigene, uruhare rw'ikinyabutabire, ibipimo by'ibisubizo, n'uko igisubizo kigaragaza uko indwara yagiye ihinduka cyangwa uko ingirabuzimafatizo zari zimeze mu gihe kimwe.

Ibyavuye mu kuvura: ibyo gutanga umuti byahinduye

Ubushakashatsi bwo kuvura bwo mu 2016 bwasohotse muri Journal of Neuroimmunology bwakoresheje imbeba z'ingore zo mu bwoko bwa C57BL/6, zifite hafi ibyumweru 8 kugeza kuri 10, zatewe urushinge rurimo 250 micrograms za MOG35-55 kuri buri mbeba. Nyuma yo gutera EAE, inyamaswa zagabanyijwe ku buryo bwa tombola mu itsinda rya methylene blue cyangwa mu itsinda rya EAE ritavuwe, maze amanota y'ibimenyetso akurikiranwa kugeza hafi y'umunsi wa 30.

Kuva ku munsi wa 15 kugeza ku munsi wa 30, amanota y'ibimenyetso yari hasi ku mbeba zavuwe ugereranyije n'imbeba za EAE zitavuwe zakoreshejwe mu kugereranya, kandi iryo tandukaniro ryari rifite agaciro mu mibare, kuri P iri munsi ya 0.01. Isuzuma ry'uruti rw'umugongo na ryo ryerekanye iyo mpinduka: mu nyamaswa zavuwe, uturemangingo dutera kubyimbirwa twinjiragamo twari duke, gutakaza myelin byari bike, no gutakaza axone byari bike.

Igice cyihariye cyari itsinda ry'ibipimo by'ubutumwa bwo mu turemangingo. Kuvura byongereye gukora kwa AMPK n'umusaruro wa SIRT1, bigabanya gukora kwa NF-kB, igenzura ry'ingenzi mu kubyimbirwa. Ku ruhande rw'ubudahangarwa bwiga guhangana n'ibyo bwahuye na byo, byagabanyije igisubizo cya Th17 kandi bikomeza igisubizo cya Treg. Uruhererekane rwatekerejwe rero ni uru: methylene blue igira icyo ihindura kuri AMPK na SIRT1, bigabanya ubutumwa bwa NF-kB, bikerekeza ubudahangarwa buva kuri Th17 itera kubyimbirwa bugana kuri Treg ibugenzura, bikagabanya kwangirika kw'ingirabuzimafatizo, bityo amanota akagabanuka.

Urwo ruhererekane ni uko ibisubizo byasobanuwe, si uruhererekane rw'impamvu n'ingaruka rwemejwe. Ubushakashatsi bwerekana ko umuti, impinduka mu butumwa bwo mu turemangingo, no kugabanuka k'ubukana bw'indwara byajyanye. Ntibwemeza ko AMPK na SIRT1 ari byo bitanga inyungu zose. Kandi inyandiko iboneka mu bubiko rusange ntisobanura bihagije ingano nyayo muri milligram per kilogram, inzira umuti watanzwemo, umunsi watangiriyeho, cyangwa igihe watanzwe, ku buryo umuntu yakongera ubwo buryo bwo gutanga umuti ashingiye ku ncamake yonyine. Ingano y'umuti iyo ari yo yose ivugwa kuri ubu bushakashatsi ku rubuga rwo kugurisha igomba gufatwa nk'itaragenzuwe, keretse iyo ishingiye ku buryo bwasobanuwe mu nyandiko yuzuye. Ibimenyetso byinshi biriho ku ikoreshwa rya methylene blue mu bantu ni byo umuntu akwiye gusuzuma kugira ngo amenye niba iki kimenyetso cy'ibanze ku budahangarwa cyarigeze gikurikirwa n'amakuru yo mu igerageza ku bantu.

Ibyavuye mu gusuzuma impinduka z'indwara: ibyo ingirabuzimafatizo zerekanye mu mezi atandatu

Ubushakashatsi bwa MP4 bwo mu 2015 bwasohotse muri PLoS ONE bwakoresheje imbeba z'ingore zo mu bwoko bwa C57BL/6, zatewe urushinge rurimo 200 micrograms za MP4 mu kinyabutabire cya Freund cyuzuye cyongera igisubizo cy'ubudahangarwa, hamwe n'uburozi bwa pertussis ku munsi w'urushinge no kongera nyuma y'amasaha 48. Nta nyamaswa yahawe methylene blue nk'umuti. Nyuma yo kubungabunga ingirabuzimafatizo no kuzishyira mu kintu gifasha kuzikata, uduce tw'uruti rw'umugongo dukase twambukiranya, dufite umubyimba wa micrometer imwe, twasizwe methylene blue kugira ngo dusuzumwe na mikorosikopi y'urumuri. Inzira y'imyakura yo ku ruhande rw'imbere yasuzumwe na mikorosikopi ya elegitoroni kugira ngo haboneke utuntu duto kurushaho.

Ingirabuzimafatizo zafashwe mu byiciro bitatu: mu gihe indwara yari igeze ku bukana bukabije bw'icyiciro cya mbere, ku mbeba 7; amezi atatu nyuma y'uko itangiye, ku mbeba 5; n'amezi atandatu nyuma y'uko itangiye, ku mbeba 10. Impuzandengo y'amanota y'ibimenyetso muri ibyo byiciro yasaga n'aho idahinduka, hafi ya 1.7 kugeza kuri 1.8 ku gipimo cya 0 kugeza kuri 5. Ariko ingirabuzimafatizo zo zerekanye ibindi. Imitsi yari ifite kwangirika kwa myelin gusa yiyongereye kuva kuri hafi 569,000 kuri square millimeter mu gihe cy'ubukana bukabije bw'icyiciro cya mbere igera kuri hafi 1,496,000 ku mezi atandatu. Kugereranya icyiciro cya mbere n'igihe kirekire byagaragaje itandukaniro rifite agaciro mu mibare, kuri P ingana na 0.027. Kwangirika gufata myelin na axone icyarimwe kwikubye hafi kabiri ku mezi atandatu. Imitsi yongeye gukora myelin yagumye munsi ya rimwe ku ijana muri buri cyiciro, kikaba ari ikintu gituma umuntu yitonda ku byiringiro byo gusana ibyangiritse.

Kwangirika kwa axone kwakurikiye ishusho ya U: kwari hejuru mu gihe cy'ubukana bukabije bw'icyiciro cya mbere, kuri hasi ku mezi atatu, hanyuma kuba hejuru kurushaho ku mezi atandatu. Kwari gufitanye isano no kubyimba kwa mitochondria no kugabanuka kw'intera hagati ya neurofilaments. Abakoze isuzuma ntibari bazi amanota cyangwa icyiciro, ibyo bikaba bishimangira umwanzuro w'uko amanota y'ibimenyetso atagaragazaga neza kwangirika kw'imiterere y'ingirabuzimafatizo kwakomezaga.

Iryo tandukaniro ni ryo musanzu w'ingenzi w'ubu bushakashatsi ku musomyi ushaka kumenya ibya MS. Amanota y'ubumuga adahinduka ntiyasobanuraga ko ingirabuzimafatizo na zo zidahinduka. Rinerekana impamvu iyi nyandiko idashobora gushyigikira icyemezo icyo ari cyo cyose cy'uko methylene blue ivura MS. Yagerageje ingaruka z'igihe, ntabwo yagerageje ubuvuzi.

Impamvu nta na bumwe muri ubu bushakashatsi bwemeza inyungu ku barwayi

Fata buri nyandiko nk'isubiza neza ikibazo gifunganye, ariko ntisubize na gato ikibazo kijyanye n'abarwayi.

Icya mbere, impamvu z'indwara ziratandukanye. EAE iterwa ku bushake hakoreshejwe antigene izwi n'ikinyabutabire cyongera igisubizo cy'ubudahangarwa. MS yo mu bantu yizana ubwayo, ikagira uruhare rw'ibice byinshi by'ubudahangarwa birimo uturemangingo T, uturemangingo B, ubudahangarwa kavukire n'uturemangingo twa glia tuba mu rwungano rw'imyakura. Ikinyabutabire gihindura igisubizo cyerekejwe cyane kuri MOG mu mbeba si ngombwa ko gihindura icyo gisubizo kigari mu bantu.

Icya kabiri, uko indwara yigaragaza biratandukanye. Intege nke mu mbeba zitangirira ku murizo zikagera ku maguru y'inyuma ni ikimenyetso cyoroshye gupima. Gishyira ubudasa bwinshi bwa MS yo mu bantu mu mubare umwe upima ubushobozi bwo kugenda. Imiti ikunze guhindura amanota ya EAE mu gihe gito ariko ntihindure uko indwara igenda mu bantu. Ni yo mpamvu EAE ari igikoresho cyo kugerageza no gusobanukirwa uburyo ibintu bikora, aho kuba ivuriro rito ryigana iby'abantu.

Icya gatatu, ingano y'umuti igera mu mubiri n'igihe utangirwa ntibirasobanuka. Gutanga umuti ubudahagarara hakiri kare mu igerageza ry'iminsi 30 ku mbeba si kimwe no kuwunywa igihe kirekire ku muntu ufite indwara yamaze gukura. Kandi nta na bumwe muri ubu bushakashatsi bwapimye ingano y'umuti iri mu rwungano rw'imyakura. Iyo iyo sano itazwi, nta buryo bwo guhuza ubwinshi bw'umuti mu gikoresho cya laboratwari cyangwa ingano yawo yahawe imbeba n'uburyo bwo kuwuhabwa ku muntu.

Icya kane, izi nyandiko ebyiri ntizisubiramo igerageza rimwe ngo zemezanye. Antigene zirandukanye, ibibazo biratandukanye, ibipimo by'ibisubizo biratandukanye, kandi muri bumwe nta buvuzi bwageragejwe na gato. Kuzivuga hamwe nk'ubushakashatsi bubiri bwatanze ibisubizo byiza ku kuvura MS ni ukwibeshya mu gushyira ibintu mu cyiciro kimwe.

Icyo ibi bisobanura ku basomyi bapima uburemere bw'ibimenyetso

Muri izi nyandiko nta buryo bwemejwe bwo gukoresha methylene blue kuri MS burimo. Ubushakashatsi bwo kuvura bushyigikira gukomeza ubushakashatsi kuri AMPK, SIRT1, NF-kB n'uburinganire bwa Th17 na Treg muri MOG EAE. Ubushakashatsi bw'impinduka z'indwara bwibutsa ko kwangirika kw'ingirabuzimafatizo gushobora gukomeza nubwo amanota asa n'adahinduka, kandi ko methylene blue ivugwa mu gice cy'uburyo bwakoreshejwe rimwe na rimwe isobanura icupa ry'irangi aho gusobanura umuti. Abasomyi bakurikirana ubushakashatsi bukomeje kuri multiple sclerosis bakwiye kuzirikana iryo tandukaniro hagati y'irangi n'umuti. Ibibazo by'umutekano, birimo ibyago bijyanye n'amaraso no gukorana nabi n'indi miti, bigomba kuganirwaho n'umuganga hamwe n'amakuru rusange ku mutekano wa methylene blue mbere y'uko umuntu agira icyo akora ashingiye ku mitwe y'inkuru z'ibyavuye muri laboratwari.

Umwanzuro ushobora kuvugwa mu nteruro imwe. Bumwe mu bushakashatsi bwavuzwe bwahaye methylene blue imbeba zifite MOG EAE, butangaza ko ubukana bw'indwara bwagabanutse hamwe n'impinduka z'ubudahangarwa zigabanya kubyimbirwa; ubundi bwo ntibwatanze umuti na mba, ahubwo bwakoresheje methylene blue gusa mu gusiga amabara ku ruti rw'umugongo, bukurikirana kwangirika kwa myelin na axone kwagendaga kwiyongera mu mezi atandatu, bityo ubu bushakashatsi bubiri ntibwemeza ko methylene blue ifasha abantu bafite MS.