Chinyorwa
Mapindiro anoita methylene blue mumasero: reduction, reoxidation, uye kugoverana mumembrane
Ukatarisa masero eendothelium ari mundiro achitora methylene blue, dudziro inoita seiri pachena ndiyo isiri iyo. Mvura yakakomberedza masero inorasikirwa neruvara rwayo rwebhuruu, masero achiwana tumapundu twebhuruu, saka zvingaita sekuti dhayi yayambuka membrane iri molekuru yebhuruu. Asi miedzo inoratidza zvakasiyana. Chimiro chebhuruu hachinyanyi kuyambuka. Chinoyambuka chimiro chisina ruvara, uye bhuruu raunoona mukati rinogadzirwa mukati, mushure mekunge dhayi yapinda.
Kusiyana uku kwakakosha nokuti ndiko kunoratidza zvinogona nezvisingagoni kukuudzwa nekusvibiswa neruvara. Tumapundu twebhuruu tunoratidza dhayi iri muchimiro cheoxidation, yakaitwazve oxidation ikavharirwa muzvikamu zviduku zviri mukati mesero zvinonzi organelles. Hatiratidzi dhayi yose iri musero, hatiratidzi huwandu huri muchimiro chereduction, uye hatiyeri zvinoitwa nedhayi mukushanda kwezvipenyu. Kuti uone chikonzero, tevera nhanho nhatu: reduction pamusoro pesero, diffusion yechimiro chakaitwa reduction, uye reoxidation nekuvharirwa mukati.
Zvimiro zviviri izvi zvinoita semamorekuru akasiyana
Methylene blue yakaitwa oxidation ine marin'i akabatana ari muchimiro chakati sandara uye ane chaji yemagetsi yakanaka. Inonyungudika mumvura, inotora chiedza zvakanyanya paurefu hwemasaisai hunosvika 600 kusvika 700 nanometers, uye inooneka iri bhuruu. Chaji ndiyo nyaya huru. Molekuru ine chaji uye inofarira mvura haiyambuki membrane yemalipid zviri nyore, saka mashoko anoshandiswa nekungwarira mumabhuku esainzi ndeokuti hainyanyi kupinda nemumembrane, kwete kuti haipindi zvachose.
Methylene blue yakaitwa reduction, inonzi leucomethylene blue, haina ruvara, haina chaji, uye inonyungudika mumafuta. Kana chaji yabviswa, membrane inorega kuita semadziro. Molekuru yakaitwa reduction inoyambuka zviri nyore nediffusion, uye kana yapinda muchikamu chine mamiriro anokurudzira oxidation, inogona kurasikirwa nemaerekitironi zvakare yodzokera kuchimiro chebhuruu chine chaji chinovharirwa mukati. Saka kemisitiri yeredox yedhayi ndiyowo nzira yekufambiswa kwayo. Ukachinja nhamba yemaerekitironi, unochinjawo kugona kwayo kuyambuka membrane.
Maerekitironi anoshandiswa panhanho yokutanga anobva musero pacharo. Masero emhuka dzinoyamwisa anofambisa maerekitironi achiyambuka membrane yeplasma, achiendesa simba rinopa reduction kubva kune zvinopa maerekitironi zviri mukati kuenda kune zvinoagamuchira zviri pamusoro pesero. Basa iri rinoyambuka membrane yeplasma rinowanzoitwa nemasero uye rinowanikwa mumhando zhinji dzemasero. Enzayimu yereductase iri pamusoro pemasero eendothelium, inoshanda nemadhayi ethiazine, yakafanana nedzimwe pane chimwe chinhu chinonyatsoratidza mashandiro ayo: inoramba ichishanda kana cyanide neazide zviripo pamadosi anomisa nhanho dzinozoitika pashure. Kupatsanurwa uku ndiko kwakakosha panyaya yose.
Kugoverana pakati pezvikamu kwakatanga kuongororwa, uye kwakapotsa kwatsanangura kutorwa kwedhayi
Muna 1929, Marian Irwin weRockefeller Institute akabvunza mubvunzo wakapfava. Zvichida kupinda kwedhayi kunongova kugoverana kwayo pakati pemvura nezvikamu zvine mafuta zvesero, uye chikamu chechloroform chinogona kumiririra zvikamu zvine mafuta izvi murabhoritari. Muongororo dzake dzekupinda kwedhayi achishandisa spectrophotometry, akazunza misanganiswa yedhayi yakanyungudutswa mumvura pamwe nechloroform, akaenzanisa chakapinda muchikamu cheorganic nezvakapinda mumasero mapenyu ealgae.
Zvinhu zviviri zvakawanikwa mubasa iroro zvichiri kufanira kutariswa. Chokutanga, misanganiswa yemethylene blue yaitengeswa yaiva netrimethyl thionine, yava kunzi azure B, uye tsvina iyi yaipinda nekukurumidza kupfuura methylene blue pachayo, kunyanya paalkaline pH apo chimiro chefree base chinonyungudika mumalipid ndicho chinonyanya kuwanikwa. Zvimwe zvaiita sekupinda kwemethylene blue zvaiva chaizvo kupinda kweazure B kwakasarudzwa nemamiriro acho. Chechipiri, pH yaitara mhedzisiro nokutara mamiriro eionization, uye masero akanga akuvara aipinza dhayi yakawanda zvikuru kupfuura akanga asina kukuvara. Partition coefficients nemamiriro echaji ndizvo zvaitonga kuti chiyedzo chakagadzirwa murabhoritari nesero benyu zvimwe nezvimwe zvaitora zvakadii. Kufanana kwezviviri izvi kwakatsigira pfungwa yokuti muganhu wesero une zvikamu zvisiri zvemvura.
Muenzaniso uyu wakanga wafanoona kukosha kwemalipid neionization, asi waisagona kusiyanisa dhayi inogoverana pakati pezvikamu isina kuchinja chimiro chayo nedhayi inoshandurwa nemaitiro ekemisitiri pamusoro pesero, yoyambuka iri muchimiro chakasiyana, yozodzoserwa kuchimiro chayo mukati. Kusiyanisa izvi kwaida mumwe muedzo, wakazoitwa makore makumi manomwe gare gare mumasero eendothelium emapapu.
Reduction kunze, kuvharirwa mukati
Merker nevamwe vake vakashanda nemasero eendothelium etsinga dzemapapu emombe akakuriswa murabhoritari, ndokupa pfungwa yenhanho nhatu dzinotevedzana: dhayi yakaitwa oxidation inoitwa reduction pamusoro pesero ichiva chimiro chayo chisina ruvara chinofarira mafuta, chimiro chakaitwa reduction chinopinda nediffusion, uye reoxidation yemukati mesero inodzorerazve chimiro chakaitwa oxidation chisingapindi nemumembrane, icho chinozoungana. Ongororo yavo yekutorwa kwethiazine nemasero eendothelium yakabva yaedza nhevedzano iyi nokuedza kuimisa panzvimbo dzakasarudzwa.
Chishandiso chokutanga chaiva ferricyanide, inogamuchira maerekitironi asi isingagoni kupinda musero. Kana maenzayimu ari pamusoro pesero akaita reduction padhayi yebhuruu kuti ive isina ruvara kunze kwesero, ferricyanide inogona kutorazve maerekitironi iwayo, ichidzorera dhayi yebhuruu mumvura yakakomberedza masero dhayi isati yayambuka. Chero bedzi ferricyanide yaivapo yakawandisa (10 micromolar yedhayi ichienzaniswa ne50 kusvika 500 micromolar yeferricyanide), kutorwa kwedhayi kwakapotsa kwamira. Kutora dhayi kwakatangazve pamwero wako wenguva dzose ferricyanide yapera chete. Kumhanya kwemaitiro aya kwakaratidza nyaya imwe chete neimwe nzira. Ferricyanide yaipera pamwero waisanyanya kuchinja, zvichienderana nereduction yairamba ichiitika pamusoro pesero ichipa maerekitironi kumurevereri aigona kudzokorora kushandiswa, ukuwo dhayi iri kunze kwesero yaipera ichitevera kuderera kweexponential sezvo huwandu hwayo hwaiderera. Kuyerera kusingachinji pamwe nehuwandu huri kuderera zvinoreva kuti chiratidzo cheferricyanide chinoratidza reduction inoenderera, kwete mamorekuru edhayi ari kubva mumvura yaakanyunguduka mairi.
Chishandiso chechipiri chakabvisa nhanho yekuyambuka zvachose. Boka iri rakasungirira toluidine blue O, iri hama yepedyo yethiazine, pacheni huru yepolyacrylamide yakanga yakakura zvokutadza kupinda musero mune chero chimiro cheoxidation. Masero akaramba achiita reduction padhayi yakanga yakasungirirwa. Saka reduction haidi kuti dhayi ipinde mukati mesero. Hurongwa hunoita basa iri huri pamusoro pesero kana kuti hwakabatana nepamusoro pesero nenzira yemagetsi.
Pakazouya kupatsanurwa kunopa bepa iri musoro waro. Cyanide neazide pa2 millimolar zvakaderedza zvikuru kuungana kwedhayi, uye pasi pemaikorosikopu, mapundu ebhuruu rakasviba nerepepuru anowanzotenderedza nucleus akapotsa anyangarika. Asi hapana chimwe chezvidzivisi izvi chakanonotsa reduction yekunze kwesero: kutenderera kweferricyanide kwakaenderera kusina kuderera, uye polymer isingapindi musero yakanga ichiri kuitwa reduction. Kumiswa kwacho kwaiva panhanho dzaitevera. Cyanide neazide zvaimisa reoxidation nekuvharirwa kwedhayi mukati mesero, kwete reduction yepamusoro pesero. Miedzo yekutarisa kuti masero akaramba ari mapenyu yakatsigira dudziro iyi, nokuti masero akachengetedza enzayimu yawo inoratidza zviri mucytosol, lactate dehydrogenase, panguva yemaitiro aya. Saka kuderera kwekutora dhayi kwakanga kusiri kungokonzerwa nechepfu kana kuputika kwemembrane.
Imwe yambiro iri mubepa iri ichiri kushanda. Mapundu ebhuruu aiva akapoteredza nucleus asi asiri mukati mayo, zvichienderana neoxidation iri kuitika mukati meorganelles. Asi ongororo yacho haina kuratidza kuti aiva maorganelles api. Kuumbwa kwakafanana mune dzimwe mhando dzemasero kwakanga kwanzi kunoitika mulysosomes pachishandiswa humbowo hushoma. Kuvharirwa kwedhayi ngakuonekwe sechinhu chakasimbiswa, asi nzvimbo chaiyo ngairambe ichionekwa seisingati yasimbiswa. Vaverengi vari kutevera kuti maerekitironi anoenda kupi pashure vanogona kuenderera kumafambisirwo emaerekitironi nemabatirwo eredox mumitochondria pamwe nemufananidzo wakafara wekutorwa nekuparadzirwa zvichienderana nenzira yekupinda.
Kusvibiswa neruvara hakusi chiyero chekusvikwa nedhayi
Ongororo yechitatu inoratidza zvinoitika kana nzira iyi yekutorwa kwedhayi ikaenzaniswa nechiyero chekushanda kwezvipenyu. Scott nevamwe vake vakawana kuti methyl beta cyclodextrin, shuga ine chimiro cherin'i, inosunga methylene blue zvakananga. Association constant yekubatana uku, apo dhayi inopinzwa mukati merin'i, inosvika 310 per molar, ichienzaniswa neinosvika 5846 per molar yekubatana kwemamorekuru maviri edhayi. Mumafibroblasts eL929, kusunga uku kwakamisa zvose kusvibiswa kwemasero neruvara nekukurudzirwa kwekutorwa kweglucose: kutanga waisa masero pamwe necyclodextrin usati wawedzera dhayi kwakadzivirira kusvibiswa nebhuruu, uye kuiwedzera pashure kwakakurumidzisa kubviswa kweruvara. Sezvo chiratidzo chebhuruu chinoonekwa nechiedza chaibva mumasero, kufambiswa kweglucose kwakanga kwakurudzirwa kwakaderera kuchinyatsofambirana nacho.
Vanyori vakadudzira kufambirana uku sekunotsigira kubatana kwakananga pakati pedhayi neprotein iri munzira inomutsa chinofambisa glucose, pane nzira inokonzerwa neoxidative stress inogara kwenguva refu. Mhedziso iyi ine musoro asi ine miganhu. Muedzo haududzi kuti protein yacho ndeipi, hauratidzi kusunga pachinofambisa glucose pachacho, uye kufambirana pakati pekubviswa kweruvara nekurasika kwechiitiko hakugoni kubvisa mukana wenzira yose inoshanda kuburikidza neredox.
Chidzidzo chinoramba chakakosha chine chekuita nekuyera. Kusvibiswa kunoonekwa nechiedza kunoratidza dhayi inooneka, iri muchimiro cheoxidation, uye yakabatana nesero. Hakuratidzi zvachose huwandu huri muchimiro chereduction chisina ruvara. Saka sero rine ruvara rusina kusimba rinogona kuramba riine dhayi mumamwe mamiriro ayo, uye sero rakasvibiswa zvakanyanya rinoratidza dhayi yakaitwa oxidation yakavharirwa mukati, kwete huwandu hwose hwedhayi hwakasvika mumatishu kana kukura kwechiitiko chayo. Yambiro imwe chete iyi inoshandawo pamwero mukuru: kuenzanisa kusvibiswa neruvara pakati pemhando dzemasero, kana kuona chidimbu chetishu chakasviba seumbowo hwekuti chakasvikwa nedhayi yakawanda, kunodzokorora chikanganiso chokutanga chedudziro yendiro. Kutorwa kwedhayi kutenderera kwereduction, diffusion, nereoxidation, uye chero mufananidzo mumwe wechimiro chebhuruu panguva imwe chete unongoona chikamu chimwe chete chekutenderera uku. Zvinorehwa nazvo pakuita kusvibisa nekubata dhayi murabhoritari uye pakududzira zvinotaurwa nezvedosi nekusvikwa nedhayi zvinobva ipapo zvakananga.