Inqaku
I-methylene blue nempilo yentliziyo: izifundo zezicwili, iimodeli zezilwanyana, nemeko yokusetyenziswa kwezonyango
Umfundi udibana neengxelo ezimbini kwiveki enye. Enye ithi i-methylene blue iphucula ukuphefumla kweemitochondria kwiintliziyo zeempuku ezinesifo seswekile. Enye ithi isetyenziswa ezibhedlele xa kusenziwa utyando lwentliziyo. Isigqibo esinokuzenzekela kukuba i-methylene blue inika intliziyo iinzuzo eziluncedo ekusileleni kwentliziyo okanye ekuyikhuseleni ngokubanzi.
Eso sigqibo sidibanisa iingcamango ezintathu ezahlukileyo. Eyokuqala sisiphumo sebhayokhemistri ngaphakathi kweemitochondria ezahluliweyo. Eyesibini lutshintsho kwikhemistri yezicwili ezingaphandle komzimba. Eyesithathu sisiphumo sezonyango kwisigulana, njengeempawu ezimbalwa, ukutyelela esibhedlele okumbalwa, okanye ukuphila ixesha elide. Nganye inomgaqo wayo wokusebenza. Isiphumo kwelinye inqanaba asidluleli ngokuzenzekelayo kwelilandelayo.
Eli nqaku liyawahlula loo manqanaba. Lihlolisisa uphando lweemitochondria zentliziyo, uphando lwezicwili zentliziyo nemithambo yegazi zabantu, uphando lwezilwanyana ezipheleleyo, kunye nemeko eyahlukileyo yasesibhedlele apho i-methylene blue ichaphazela ukujikeleza kwegazi.
Itheyibhile yobungqina obuphathelele intliziyo
Le theyibhile sisikhokelo esiphambili sesi sihloko. Yahlula amalungiselelo ezicwili ezahluliweyo, izilwanyana ezipheleleyo, kunye neemeko zonyango kuba ziphendula imibuzo eyahlukileyo.
| Inqanaba lobungqina | Oko kwavavanywayo | Oko kwatshintshayo | Oko kungakungqiniyo |
|---|---|---|---|
| Iimitochondria zentliziyo ezahluliweyo, kwiimpuku ezinesifo seswekile nezisempilweni | I-methylene blue eyi-0.1 micromolar yongezwa okwethutyana kwiimitochondria ezinikwe iisubstrate zekh ompleksi I okanye zekh ompleksi II | Ukusetyenziswa kweoksijini kwenyuka ngeentlobo zombini zeesubstrate. Ukukhutshwa kwehydrogen peroxide kwenyuka ngeesubstrate zekh ompleksi I kwaza kwehla ngesuccinate, isubstrate yekhompleksi II. Ukugcinwa kwecalcium akuzange kutshintshe. | Akubonisi ukuphucuka kokumpompa kwentliziyo, kweempawu, okanye kokuphila kwisigulana esiphilayo. Eli lungiselelo alinakho ukuhamba kwegazi kwimithambo yentliziyo, ulawulo loxinzelelo lwegazi, izintso, imithambo-luvo, okanye ukusebenzisana kwamayeza. |
| Intliziyo epheleleyo yempuku enesifo seswekile, enikwa idosi ixesha elide | I-methylene blue eyi-10 mg nge-kg ngosuku, kunye ne-echocardiography, uphononongo lokuhamba kwegazi, umlinganiselo wokuphefumla, nohlalutyo lweeproteni | Ioksideshini ye-NADH yanda, i-NAD yenyuka, ukusebenza kwe-sirtuin 3 kwenyuka, kwaza ukongezwa kwamaqela e-acetyl kwi-lysine kwehla kwiindawo eziyi-83 kwiiproteni zeemitochondria eziyi-34. Ioksideshini yeeasidi zamafutha yatshintsha kwaye ukusebenza kwentliziyo kwaphucuka kwizilwanyana ezinesifo seswekile. Isiphene sekhompleksi I esinxulumene nesifo seswekile ngokwaso asizange silungiswe. | Akungqini ukuba i-methylene blue lunyango lokusilela kwentliziyo ebantwini. Uhlobo lwesilwanyana, imodeli yesifo seswekile, idosi, kunye nemilinganiselo esetyenziswa endaweni yeziphumo zokwenene kuthintela ukudluliselwa ngokuthe ngqo ekusileleni kwentliziyo yabantu. |
| Amafutha entliziyo nemithambo yegazi yabantu, ngaphandle komzimba | Amafutha aphezu kwentliziyo najikeleze imithambo yegazi, athathwe kwizigulana eziyi-25 ezinokusilela kwentliziyo nezazisenziwa utyando lwentliziyo, agcinwa ne-methylene blue eyi-0.1 micromolar kangangeeyure eziyi-24 | Zombini iintlobo ze-monoamine oxidase zazikho, ingakumbi i-MAO-A. I-methylene blue yanciphisa ukuveliswa kwe-MAO neentlobo zeoksijini ezisebenza ngamandla. Iserotonin eyongeziweyo yandisa ihydrogen peroxide nge-MAO-A, kwaye i-methylene blue yalunciphisa ngokuyinxenye olo lwando. | Izicwili ezingaphandle komzimba azilolingo lonyango. Akubonisi ukuba ukuthatha i-methylene blue kuphucula ukusebenza kweeventricle okanye iziphumo zonyango. |
| Izinja ezipheleleyo nezisezingqondweni xa zizilolonga | Idosi yokuqala elandelwa kukufakwa okuqhubekayo kwe-methylene blue entsha ngomthambo xa zizilolonga kumatshini wokubaleka, kuthelekiswa nesisombululo setyuwa | Umlinganiselo welactate kwipyruvate egazini lemithambo yehla, ubonisa utshintsho lwe-redox, ngoxa umthamo wegazi ompompywa yintliziyo, isantya sentliziyo, amandla okushwabana, uxinzelelo lwemithambo yegazi, kunye neempendulo zeecatecholamine xa zizilolonga zingazange zitshintshe. | Akuxhasi ukuphucuka kwamandla okuzilolonga okanye ukusebenza kwentliziyo ngenxa yotshintsho lwe-redox. Izinja zazingenako ukusilela kwentliziyo okuxilongwe kwezonyango. |
| Iimeko zasesibhedlele zokulawula ukuhamba kwegazi | I-methylene blue efakwa ngomthambo (IV) yevasoplegia emva kotyando lwentliziyo, ukhathalelo olongezelelweyo lomothuko obangelwa lusulelo, kunye nonyango olunelayisensi lwemethemoglobinemia efunyenweyo | Uxinzelelo lwegazi oluphakathi kwimithambo nokuxhathisa kwemithambo yegazi kunokunyuka, kwaye imfuneko yeevasopressor inokwehla kwiimeko ezikhethiweyo zomothuko obangelwa kukwandiswa kwemithambo yegazi. Imethemoglobin iyehla kwimethemoglobinemia, ibuyisela ukuthuthwa kweoksijini. | Inkxaso ye-IV yexesha elifutshane yoxinzelelo okanye yokuthuthwa kweoksijini ayibobungqina bonyango oluthathwa ngomlomo ixesha elide lwesifo semithambo yentliziyo, iatherosclerosis, okanye ukusilela kwentliziyo. Indlela yokuyinika, idosi, ixesha, nesifo ziyahluka. |
Funda ikholamu yokugqibela kuqala. Loo kholamu iqulethe ulungiso lwendlela yokucinga olushiywayo ziingxelo ezininzi zamabango nge-methylene blue nentliziyo.
Oko kuboniswa ziimitochondria zentliziyo ezahluliweyo
Uphononongo lwentliziyo enesifo seswekile lwavavanya iimitochondria ezikhutshwe kwiimpuku ezisempilweni nakwiimpuku ezinesifo seswekile esibangelwe yistreptozotocin. Umlinganiselo wokuphefumla ochaneke kakhulu walinganisa ukusetyenziswa kweoksijini. Iimvavanyo zokukhanya kwefluorescence zalinganisa ihydrogen peroxide nokulawulwa kwecalcium.
Into eluncedo nengalindelekanga kukuxhomekeka kwisubstrate. Ngeglutamate kunye nemalate, ezibonelela ikhompleksi I, i-methylene blue yandisa ukuphefumla kodwa yandisa nokukhutshwa kwehydrogen peroxide. Ngesuccinate, ebonelela ikhompleksi II, yandisa ukuphefumla yaza yanciphisa ihydrogen peroxide. Ngoko igama elithi antioxidant aliyichazi yonke indlela esebenza ngayo. Ukunyuka okanye ukwehla kweentlobo zeoksijini ezisebenza ngamandla kuxhomekeke kwindlela yokuphefumla esebenzayo nakwimeko ye-redox ye-coenzyme Q.
Uphononongo olunxulumeneyo lweempuku ezinesifo seswekile luyicacisa ngakumbi indlela yokusebenza. I-methylene blue isebenza njengenye indlela yokuthwala iielektroni. Inceda ukwenza ioksideshini ye-NADH ibe yi-NAD, nto leyo eyandisa ukusebenza kwe-sirtuin 3, i-enzyme yeemitochondria esusa amaqela e-acetyl. Le enzyme isusa amaqela e-acetyl kwiintsalela ze-lysine ezikwiiproteni zeemitochondria. Uhlalutyo lweeproteni lwafumana ukuncipha kokongezwa kwamaqela e-acetyl kwiiproteni ezibandakanyeka ekuthuthweni nasekwenziweni kweoksideshini yeeasidi zamafutha, kumjikelo we-tricarboxylic acid, ekuthuthweni kwee-elektroni, kwimetabolism yeeamino acid, nasekuthuthweni kwezinto. Ukusebenza kwentliziyo kwaphucuka kwiimpuku ezinesifo seswekile ezanyangwayo nangona isiphene esisisiseko sekhompleksi I sasisekhona.
Cinga ngale nto njengokutshintsha indlela yee-elektroni kunokuba ibe kukususa nje iiradical. Isikhokelo sokuthuthwa kwee-elektroni kwiimitochondria sibeka le ngcamango yokutshintsha indlela kwikhonkco elibanzi. Oku kusese yingcaciso yenqanaba lezicwili, kungekhona umyalelo wonyango.
Oko kongezwa zizicwili zentliziyo yomntu, noko zingenakukongeza
Uphononongo lwabantu lusondela inyathelo elinye kwizigulana ngaphandle kokuba lulingo lonyango. Oogqirha botyando baqokelela amafutha e-epicardial, ahleli ngqo phezu kwentliziyo, namafutha e-perivascular, ajikeleze imithambo yegazi, kwizigulana ezinokusilela kwentliziyo. Elebhu, iisampulu zagcinwa ne-methylene blue yoxinaniso oluphantsi kangangosuku olunye.
Zombini izicwili zazivelisa ii-enzyme ze-monoamine oxidase, ingakumbi uhlobo lwe-MAO-A. Ezi enzyme zinokuvelisa iintlobo zeoksijini ezisebenza ngamandla kuloo ndawo. I-methylene blue yanciphisa ukuveliswa kwe-MAO yaza yehlisa iimpawu zoxinzelelo lweoksideshini. Xa abaphandi bongeza iserotonin, isubstrate ye-MAO-A, ihydrogen peroxide yenyuka. I-methylene blue yalunciphisa ngokuyinxenye olo lwando.
Oku kubalulekile kuba amafutha ajikeleze intliziyo nemithambo yegazi ngoku ajongwa njengomthombo osebenzayo weempawu zokudumba nezeoksideshini kwizifo zentliziyo nemetabolism, kungekhona nje izinto zokugcwalisa ezingasebenziyo. Uphononongo luchonga isiphumo esinokwenzeka se-methylene blue kuloo ndawo kwizicwili zokwenene zabantu.
Lo mda usasebenza. Iisampulu ezingamashumi amabini anesihlanu ezithathwe ngexesha lotyando, zanyangwa ngaphandle komzimba kangangeeyure eziyi-24, azinakubonisa ukuba i-methylene blue eginyiweyo ifikelela kuloo ndawo kuxinaniso olusebenzayo, ihlala apho ngokukhuselekileyo, itshintsha ukusebenza kwentliziyo, okanye iguqula iziphumo. Ngemigaqo ngokubanzi exhasa loo mda, jonga indlela yokufunda uphando lwe-methylene blue.
Oko kuboniswa luphononongo lokuzilolonga lwezilwanyana ezipheleleyo
Uphononongo lwezinja luxabisekile ikakhulu njengesiphumo esingabonisi phuculo. Izinja ezisezingqondweni zabaleka kumatshini wokubaleka kumanqanaba amabini omsebenzi. Elinye iqela lanikwa isisombululo setyuwa. Elinye lanikwa idosi yokuqala ye-methylene blue elandelwa kukufakwa okuqhubekayo ngomthambo. Elesithathu lanikwa i-methylene blue ngaphandle kokuzilolonga.
I-methylene blue yawunciphisa ngokwenene umlinganiselo welactate kwipyruvate egazini lemithambo, umlinganiselo onxulumene nolungelelwaniso lwe-NADH ne-NAD. Umthamo wegazi ompompywa yintliziyo xa iphumle, isantya sentliziyo, uxinzelelo, kunye nemilinganiselo yamandla okushwabana yatshintsha kancinane. Ngexesha lokuzilolonga, umthamo wegazi ompompywa yintliziyo waphindeka kabini kwaye ukusetyenziswa kweoksijini ngumzimba wonke kwanda kathathu ukuya kane kuwo omabini amaqela, elesisombululo setyuwa nele-methylene blue. Unxulumano phakathi komthamo wegazi ompompywa yintliziyo nokusetyenziswa kweoksijini aluzange lutshintshwe yi-methylene blue.
Ngokweengcamango, inkqubo ye-redox yatshintsha ngoxa inkqubo yokumpompa ingazange itshintshe. Utshintsho lwebhayokhemistri alunyanzelekanga ukuba lutshintshe impendulo edibanisa iinkqubo ezininzi, njengomthamo wegazi ompompywa yintliziyo xa kuzilolongwa. Oku kwahlulwa kuhambelana ngokuthe ngqo namabango okuba amanani angcono eemitochondria amele ukuthetha intliziyo enamandla ngakumbi xa kusenziwa umsebenzi.
Ukusetyenziswa esibhedlele kwahlukile kunyango lwexesha elide
Izibhedlele zisebenzisa i-methylene blue ye-IV kwiimeko ezintathu ezivakala zinxulumene nentliziyo kodwa ezivavanya imibuzo eyahlukileyo.
Okokuqala, ivasoplegia emva kotyando lwentliziyo ithetha ukulahleka kakhulu kokuqina kwemithambo yegazi nangona intliziyo impompa ngokwaneleyo. Iimvavanyo zazidla ngokusebenzisa malunga ne-1.5 ukuya kwi-2 mg nge-kg nge-IV, zifakwe kanye ngomthambo. Isiphumo esiphindaphindiweyo luxinzelelo oluphakathi oluphezulu nokuxhathisa kwemithambo yegazi okuphezulu, kunye nokuncipha kwemfuneko yeevasopressor, ngaphandle kokunyuka okungaguquguqukiyo komthamo wegazi ompompywa yintliziyo. Uhlaziyo oluneenkcukacha lweemvavanyo lukwi phepha lobungqina bevasoplegia nomothuko obangelwa lusulelo.
Okwesibini, ukhathalelo olongezelelweyo lomothuko obangelwa lusulelo lusebenzisa iinkqubo ezahlukeneyo ze-IV, kuquka inkqubo yango-2023 ye-100 mg efakwa ngomthambo kwisithuba seeyure ezintandathu yonke imihla, kangangeedosi ezintathu. Ixesha eliphakathi ukuya ekuyekisweni kweevasopressor lehla ukusuka kwiiyure eziyi-94 ukuya kweziyi-69, ngoxa ukufa nexesha lokuncediswa ngokuphefumla zazifana. Uhlalutyo lwamva oludibanisa izifundo lucebisa ukuba kungakho uphawu lokuncipha kokufa kwixesha elifutshane, kodwa luthi ukuqiniseka kusezantsi kwaye kuxhomekeke kakhulu ekukhethweni kweemvavanyo. Ibango elomeleleyo kukunciphisa ukusetyenziswa kweevasopressor, kungekhona ukwanda kokuphila okungqiniweyo.
Okwesithathu, imethemoglobinemia efunyenweyo yimeko evunyelwe ngokusemthethweni ukunyanga nge-IV, ngokuqhelekileyo nge-1 mg nge-kg nge-IV, nedosi enye ephindwayo xa kuyimfuneko. Apha i-methylene blue ibuyisela ukusebenza kwehemoglobin nokuhanjiswa kweoksijini. Iimpawu zesifuba ziyaphucuka kuba ukuthuthwa kweoksijini kuyaphucuka, kungekhona kuba i-methylene blue ilungisa ngokutsha ubume bentliziyo.
Akukho nanye kwezi meko evavanya i-methylene blue ethathwa ngomlomo yonke imihla yokusilela kwentliziyo okungapheliyo, isifo semithambo yentliziyo, okanye ukuthintela izifo. Iindlela zangoku zokunyanga ukusilela kwentliziyo nesifo semithambo yentliziyo aziyidwelisi njengonyango olucetyiswayo lwexesha elide. Ubungqina boxinzelelo lwegazi benza umahluko ofanayo kwindlela yokuyinika nakwimeko yokuyisebenzisa xa kuthethwa ngokuqina kwemithambo yegazi: impendulo yoxinzelelo kwi-IV xa kukho umothuko ayiqikeleli impendulo enokulinganiswa ngesixhobo sasekhaya soxinzelelo lwegazi emva kokuthatha imveliso ngomlomo.
Naluphi na udibaniso lwexesha elizayo lwamabango ngezifo ezingapheliyo luya kufuna idatha yolingo olwabela abantu kumaqela ngokungakhethiyo ngeempawu, ukusebenza, ukulaliswa esibhedlele, nokhuseleko ngenkqubo yokwenene yokuyithatha ngomlomo, kungekhona olunye uvavanyo lweemitochondria.
Imibuzo yokhuseleko abafundi abaneemeko zentliziyo abafanele bayicacise kuqala
Izigulana zentliziyo zidla ngokuthatha amayeza amaninzi asebenzisanayo. Kufuneka kuqale ukuhlolwa izinto ezintathu zokhuseleko ngaphambi kokuba kubekho ithemba ngenxa yendlela esebenza ngayo.
Okokuqala, i-methylene blue sisithinteli esinamandla se-monoamine oxidase. Ileyibhile ye-IV inesilumkiso esisebhokisini ngeserotonin syndrome xa isetyenziswa kunye nee-SSRI, ii-SNRI, izithinteli ze-MAO, kunye neeopioid ezininzi. Iimpawu ziquka ukuphazamiseka okwenza umntu angazolisi, ukudideka, umkhuhlane, ukubila, isantya sentliziyo okanye uxinzelelo olungazinzanga, ukungcangcazela, ukuqina kwezihlunu, kunye ne-clonus. Izigulana zentliziyo kufuneka zizise uluhlu olupheleleyo lwamayeza kugqirha okanye kusokhemesti, kwaye akufanele ziyeke ngokwazo amayeza okudakumba okanye eentlungu.
Okwesibini, ukunqongophala kwe-glucose-6-phosphate dehydrogenase yimeko engakuvumeliyo ukusetyenziswa kwayo kuba i-methylene blue inokubangela ukuqhekeka okukhulu kweeseli ezibomvu zegazi. Ukufunda okuqhelekileyo kwesixhobo sokulinganisa ioksijini egazini akukwazi ukukhupha lo mngcipheko. I-methylene blue inokuphinda igqwethe ukufunda kwezi zixhobo nezinye izixhobo zokubeka iliso xa kusetyenziswa iyeza lokulalisa ngexesha lotyando, nto leyo esesinye sezizathu zokuba ukusetyenziswa esibhedlele kwenziwe phantsi kokubekwa iliso.
Okwesithathu, ukuqiqa ngeendlela zebhayokhemistri akusosikhokelo seedosi. Iinitrate zisebenza ngenitric oxide ne-cyclic GMP. I-methylene blue inokunciphisa ukukhululeka kwemithambo yegazi okubangelwa yinitric oxide kwiimvavanyo, kodwa oko akubonisi ukuba inokuchasana ngokukhuselekileyo nenitrate okanye ithathe indawo yeyeza lentliziyo elimiselweyo. Iziphumo zoxinzelelo lwegazi ezixeliweyo nge-methylene blue ye-IV ziquka zombini uxinzelelo oluphezulu noluphantsi, kunye nesantya sentliziyo esikhawulezayo nokubetha kwentliziyo okungaqhelekanga, ngoko ukubekwa iliso kubalulekile.
Umgaqo osebenzayo ulula. Iziphumo zezicwili nezezilwanyana zizizathu zokwenza iimvavanyo ngononophelo, kungekhona izizathu zokuzinyangela imeko yentliziyo. Nabani na onokusilela kwentliziyo, isifo semithambo yentliziyo, ukubetha kwentliziyo okungaqhelekanga, okanye isixhobo sentliziyo kufuneka axoxe neqela leengcali zentliziyo ngako nakuphi na ukuchanabeka kwi-methylene blue, kubhalwe imveliso, uxinaniso, isixa, indlela yokuyinika, ixesha, kunye neempawu.