Chinyorwa
Methylene blue nemasero anotsigira uropi: astrocytes, microglia, uye kuzvimba
Ngatiti unoita miedzo miviri nedhayi yebhuruu imwe chete, wowana mhinduro mbiri dzinokurudzira. Mundiro imwe, masero anotsigira ane chimiro chenyeredzi anopona kana abvisirwa okisijeni neglucose. Mune imwe, masero anodzivirira uropi anoramba aine chimiro chawo chine mapazi, chinoonekwa paanenge asina kumutswa, pasinei nechepfu yemabhakitiriya. Zviri nyore kuda kubatanidza izvi woti chinhu chimwe chete: dhayi inoderedza kuzvimba muuropi uye inodzivirira uropi. Pakubatanidza uku ndipo chaipo panofanira kumbomira vaverengi vanongwarira.
Uropi hune mapoka maviri emasero anotsigira ane mabasa akasiyana, uye methylene blue inoongororwa pane rimwe nerimwe pachishandiswa chinokonzera chakasiyana mumuedzo. Astrocytes masero anotsigira maitiro ekushandisa simba nezvinovaka muviri. Anogara pakati petsinga dzeropa nemasero etsinga, anobvisa glutamate yakawandisa, anodzikamisa huwandu hwepotassium, anochengeta glycogen, uye anoendesa zvinopa simba kumasero etsinga panokwira zvinodiwa. Microglia ndiwo masero anodzivirira anogara muuropi achiongorora. Mapazi awo madiki anorinda nyama, anoona zviratidzo zvemabhakitiriya nezvekukuvadzwa, uye kana paine chenjedzo anodzokera mukati, sero rova nedenderedzwa rakafanana neamoeba, rakagadzirirwa kufamba nekumedza zvinhu uku richiburitsa mamorekuru anotumira zviratidzo. Zvakawanikwa muboka rimwe hazvibvi zvashanda kune rimwe, uye chiyero chakashandiswa muchiitiko chimwe nechimwe ndicho chinoratidza zvakanyatsoratidzwa.
Astrocytes pakushushikana kwemaitiro ekushandisa simba: nguva ndiyo yakakosha pazvakawanikwa
Muedzo weastrocytes unotanga nekushayiswa zvinodiwa. Vatsvakurudzi vakarera murabhoritari astrocytes emugoko reuropi kubva kumbeva dzichangoberekwa, vakabvisa glucose neinoda kusvika okisijeni yose kwemaawa matanhatu, vozodzosa zvose kwemaawa makumi maviri nemana. Uyu muenzaniso wemurabhoritari wesitiroko inoteverwa nekudzoka kwekuyerera kweropa. Methylene blue payaivapo panguva yekushayiswa uku, kupona kwemasero kwakaderera. Payakawedzerwa chete panguva yokudzorerwa kweokisijeni, pa0.1 ne1 micromolar, kupona kwakavandudzika zvakakosha maererano nekuongororwa kwekurarama kwemasero necalcein. Chidzidzo cheastrocytes dzembeva chinotsanangura musiyano uyu wenguva pamwe chete nemashoko ekufema kwemasero.
Musiyano iwoyo ndiwo wakanyanya kukosha pane zvakawanikwa. Panguva yekushayiswa, panenge pasina okisijeni yokugamuchira maerekitironi, saka nzira yekuatambidza haina kwaanoendeswa. Pakudzorerwa kweokisijeni, michina yesero inotangazve kushanda uye dhayi inenge iine basa rekuita. Astrocytes dzakapiwa dhayi dzakashandisa okisijeni yakawanda, dzakatora glucose yakawanda, dzakagadzira ATP yakawanda, uye dzakavakazve matura eglycogen, paine kuwedzera kwekushanda kwehexokinase asi pasina kukwira kwesuperoxide mumitochondria. Tsananguro yakatsanangurwa ndeiya inozivikanwa kubva mutsananguro yemethylene blue semutakuri wemaerekitironi mumitochondria: inotakura maerekitironi ichiapfuudza nzvimbo dzakavharika mucheni yekufema kwemasero, kuitira kuti kufema kutangezve zvakanaka pane kuti maerekitironi abude achipinda mumamorekuru anoshanda zvakanyanya.
Cherechedza kuti uhwu uchapupu hwerudzii. Imhinduro yekupona nemaitiro ekushandisa simba nezvinovaka muviri mumhando imwe yesero yakaparadzaniswa, ine nguva yakatarwa yekushanda zvakanaka (pakupora, kwete pakushayiswa) uye uwandu hwakatarwa hwemushonga. Haitauri chinhu pamusoro pekutumira zviratidzo zvekudzivirirwa kwemuviri, uye haitauri chinhu pamusoro pemaitiro.
Microglia pachenjedzo yemabhakitiriya: kuchinjwa kwemaitiro ekushandisa simba
Miedzo yemicroglia inotanga nechinokonzera chakapesana neicho: kwete kushaya chikafu, asi chiratidzo chenhema cheutachiona. Lipopolysaccharide, chidimbu chegoko rekunze remabhakitiriya, inosunga pazvinonzwa zviratidzo zvehurongwa hwekudzivirira hwatinoberekwa nahwo, yoita kuti microglia aone sokuti utachiona hwasvika, kunyange pasina mabhakitiriya mapenyu. Mumbeva dzakapiwa lipopolysaccharide uye mumutsara wemasero emicroglia akarerwa murabhoritari, panobuda maitiro anozivikanwa ekuzvimba: zvinhu zvinokurudzira kuzvimba zvinokwira, microglia anorerekera kumamiriro ane hasha eM1, masero etsinga ari pedyo anofa, uye mhuka dzinoita zvakaipisisa pamabasa ekudzidza nekuyeuka.
Chidzidzo chekupindura uku mumbeva chinochitevera kusvika panzira inonzwa okisijeni: lipopolysaccharide inokonzera kugadzirwa kwePHD3 yakawandisa, imwe yemaenzayimu matatu eprolyl hydroxylase, kuburikidza necheni yeSiah2/Morg1 iri pamberi payo munzira iyi. Panguva imwe chete, masero anochinja mashandisiro awo esimba achienda kuglycolysis inoitika paine okisijeni, pamwe nekukwira kwemamorekuru eokisijeni anoshanda zvakanyanya mumitochondria. Vanyori vakayera shanduko iyi zvakananga nemiedzo yeSeahorse yemaitiro ekushandisa simba, vachiongorora kushandiswa kweokisijeni nekuwedzera kweasidhi kunze kwemasero. Methylene blue yakadzosera kumashure zvose shanduko yemaitiro ekushandisa simba nekugadzirwa kwePHD3 yakawandisa, ikaderedza zvinhu zvinokonzera kuzvimba, ikaderedza kufa kwemasero etsinga, uye ikavandudza zvibodzwa zvemaitiro. Positron emission tomography yakawedzera uchapupu hwemifananidzo: lipopolysaccharide yakakwidza kutorwa kweglucose muhippocampus paFDG-PET, uye kurapwa kwakaidzikisazve, zvichienderana nekudzikama kwemaitiro ekushandisa simba ane chekuita nekuzvimba muuropi huri mumhuka mhenyu.
Iyi ine zviyero zvakawanda kupfuura chidzidzo cheastrocytes (cytokines, maitiro ekushandisa simba, mifananidzo, nemaitiro emhuka), asi ndeyechinokonzera chakasiyana uye sero rakasiyana. Vaverengi vanofananidza zviviri izvi vanofanira kuramba vakaparadzanisa zvinokonzera: chimwe chidzidzo chinoponesa masero anotsigira anoshaya chikafu panguva yekupora; chimwe chinoderedza chenjedzo yenhema yeutachiona mumasero anodzivirira.
Microglia pasi pemaikorosikopu: chimiro sechiyero
Muedzo wechitatu unoongorora chenjedzo imwe chete yemabhakitiriya uchishandisa chimiro chete. Mumasero eglia akarerwa kubva mugoko reuropi hwemakonzo, microglia eboka rekuenzanisa akapendwa kuti aratidze mucherechedzo weIBA1 anoratidza mapazi madiki mazhinji, chimiro chine mapazi chinoongorora zvakapoteredza. Pashure pemaawa makumi maviri nemana elipopolysaccharide pa10 micrograms per milliliter, masero anoti sandara oita chimiro chakafanana neamoeba, uye nzvimbo inofukidzwa nemuviri wesero inokura uku kureba kwemuganhu wayo kuchiramba kwakada kufanana. Ichi chiratidzo chejiyometri chekuita denderedzwa. Methylene blue pa1 micromolar, yakapiwa pamwe chete nechepfu, yakachengetedza mapazi uye ikaita kuti nzvimbo inofukidzwa nemuviri wesero nekureba kwemuganhu wayo zvirambe zviri pedyo nezviyero zveboka rekuenzanisa. Chidzidzo chemasero emakonzo akarerwa murabhoritari chinoyera kuchengetedzwa uku kwechimiro nenzvimbo inofukidzwa nemuviri wesero nekureba kwemuganhu wayo.
Zvinhu zviviri zvinoita kuti chidzidzo ichi chive chakakosha kupfuura mufananidzo chete. Chekutanga, menadione yakashandiswa kuenzanisa, rimwe morekuru rinobatanidzwa mukuchinjana kwemaerekitironi pahuwandu humwe chete, haina kuchengetedza chimiro uye pachayo yakasundira masero kumamiriro ekumutswa. Saka izvi hazvisi zvinhu zvinongowanikwa pamamorekuru ose anotenderera achigamuchira nekupa maerekitironi. Chechipiri, vanyori vanobatanidza kushanda kwedhayi nekumutswa kweNrf2, puroteni inodzora kuverengwa kwemajini inotungamirira maitiro emajini anodzivirira kukuvadzwa neoxidation uye anodzora kuzvimba, kwete nekubvisa mamorekuru anoshanda zvakanyanya zvakananga chete. Dzimwe tsananguro dzine chekuita nekuchinjana kwemaerekitironi nekutumira zviratidzo zvekuzvimba dzinoisa kubatana uku neNrf2 mumamiriro acho.
Zvisinei, chimiro ndicho chiyero chine uchapupu hushoma pazvitatu izvi. Sero rine mapazi rinowanzova sero rinoongorora, uye sero rakatenderera rinowanzova rakamutswa, asi chimiro chinongomirira mamwe maitiro, hachisi rondedzero yekuverengwa kwemajini. Muunganidzwa uyu wemasero wakanga usina masero anodzivirira anotakurwa neropa, usina dandemutande rekubatana kwetsinga, uye usina migumisiro yemaitiro.
Kuverenga zvakawanikwa zvitatu padivi nepadivi
| Chinokonzera | Mhando yesero | Zvakayerwa | Zvakaitwa nemethylene blue |
|---|---|---|---|
| Okisijeni neglucose zvakabviswa, zvobva zvadzorerwa | Astrocytes dzembeva | Kurarama kwemasero, kushandiswa kweokisijeni, kutorwa kweglucose, ATP, glycogen, superoxide | Yakadzivirira chete payakapiwa pakudzorerwa kweokisijeni; yakakwidza kufema kwemasero nematura pasina kukwidza superoxide |
| Chidimbu chechepfu yemabhakitiriya | Microglia dzembeva, mumasero akarerwa murabhoritari uye mumbeva mhenyu | Cytokines, zvicherechedzo zveM1, maitiro ekushandisa simba akaongororwa neSeahorse, mapuroteni enzira yePHD3, FDG-PET, mabasa ekuyeuka | Yakadzosera kumashure kuchinjwa kwemaitiro eglycolysis nekugadzirwa kwePHD3 yakawandisa; yakaderedza kuzvimba; yakavandudza maitiro |
| Chidimbu chechepfu yemabhakitiriya | Microglia dzemakonzo mumusanganiswa wemasero eglia akarerwa murabhoritari | Nzvimbo inofukidzwa nemuviri wesero rinoratidza IBA1, kureba kwemuganhu wayo, kupararira kwemapazi | Yakachengetedza chimiro chine mapazi chemasero asina kumutswa; menadione haina kudaro |
Chinoratidzwa nemitsara iyi ndechekuti chinokonzera chimwe nechimwe chine chiyero chacho nemhinduro yacho. Kununurwa kwemaitiro ekushandisa simba kunopindura mubvunzo wemaitiro ekushandisa simba. Mashoko ecytokines nemaitiro anopindura mubvunzo wekuzvimba. Chimiro chinopindura mubvunzo wechimiro. Hapana pazvitatu izvi chinoyambuka choga chichipindura mibvunzo yezvimwe.
Zvisingaratidzwi nemicroglia anotaridzika akadzikama
Uyu ndiwo mutsara unodiwa nemusoro wose uyu: microglia anotaridzika asina kumutswa zvakanyanya, kana kuchinjwa kwemaitiro awo ekushandisa simba, hazviratidzi pachazvo kuti kushanda kweuropi kwavandudzika.
Chimiro chinogona kuchinja basa risingateveri. Sero rinogona kuramba riine mapazi aro richiri kuburitsa cytokines, kana kuita denderedzwa richibvisa zvimedu zvakasara zvinofanira kubviswa. Zviyero zvemaitiro ekushandisa simba zvine muganhu mumwe chete: girafu reSeahorse kana mufananidzo wePET zvinoratidza mashandisirwo esimba, kwete kugona kufunga. Chidzidzo chembeva chakabatanidza zviyero zvemaitiro ekushandisa simba nezvakaita sezviyero zvechimiro nemiedzo yemaitiro chine uchapupu hwakasimba chaizvo nokuti chakabatanidza mazinga akawanda euchapupu pane kuda kuti chiyero chimwe chete chitsigire mhedziso yose. Kunyange ipapo, miganhu inowanzozivikanwa ichiripo, nokuti lipopolysaccharide inotevedzera chenjedzo isina utachiona hupenyu pane chirwere chaicho cheutachiona, mbeva hadzisi vanhu, uye vanyori pachavo vanotaura nezvemisiyano pakati pemarudzi. Ani naani ari kuronga basa rinotevera anofanira kufunga kuti zvakawanikwa pamicroglia zvinofambiswa sei pakati pemienzaniso yakasiyana asati afungidzira kuti nzira yacho inoshanda zvakafanana munyama yemunhu.
Pane mhedziso inoshanda inotevera pamusoro penguva. Zvakawanikwa paastrocytes zvinoratidza kuipa kwekupa mushonga nokukurumidza uye kunaka kwekuupa panguva yekupora. Zvakawanikwa pamicroglia zvinobva pakupa mushonga pedyo nenguva yechinokonzera kuzvimba. Kukuvadzwa kweuropi muupenyu chaihwo kunosanganisa zvikamu zvose izvi panguva imwe chete: kutadza kuwana simba pamwe nechenjedzo yehurongwa hwekudzivirira, zvichishanduka nekufamba kwemaawa. Muedzo unoparadzanisa chikamu chimwe chete haugoni kugadza nguva yekupa mushonga pachinoitika chine zvikamu zvose zvakabatanidzwa. Ndokusaka hurukuro dzenguva dzakakodzera kupa mushonga dzichichengeta nguva dzekushayiswa nedzekuzvimba dzakaparadzana.
Pfupiso yakatendeseka inokwana mundima imwe. Muastrocytes dzakaparadzaniswa, methylene blue inopiwa pakudzorerwa kweokisijeni inotangazve kufema kwemasero uye inoponesa masero. Mumicroglia akaiswa pasi pechidimbu chebhakitiriya, inodzosa kumashure maitiro ekushandisa simba ane chekuita nekuzvimba kuburikidza nenzira chaiyo yePHD3 uye inochengetedza chimiro chemasero asina kumutswa. Chimwe nechimwe chezvakawanikwa ichokwadi mukati memamiriro emuedzo wacho, uye hapana chimwe chinopa mutongo wakazara pamusoro pekuzvimba muuropi. Kuenzanisa masero eglia kunobatsira chaizvo nokuti kunodzivirira nyaya mbiri idzi kuti dzisavhiringidzwe dzichiitwa imwe chete.