Te urunga o te kikorangi metilīni ki ngā pūtau: te whakahekenga, te whakahāoratanga anō, me te tohatoha ki te kiriuhi

Mātakitakihia he ipu pūtau endothelium e kapo ana i te kikorangi metilīni, ā, ko te whakamāramatanga e tino kitea ana he whakamāramatanga hē hoki. Ka ngaro te tae kikorangi o te wē whakatipu, ka puta he granule kikorangi ki ngā pūtau, nō reira ko te whakaaro kua whakawhiti te waikano i te kiriuhi hei rāpoi ngota kikorangi. He rerekē tā ngā whakamātautau e whakaatu ana. He iti noa te whakawhitinga o te āhua kikorangi. Ko te āhua kore tae kē ka whakawhiti, ā, ko te kikorangi ka kitea ki roto ka hangaia ki roto, i muri i te taenga atu.

He mea nui tēnei hurihanga o te whakaaro, nā te mea mā reira e whakatau he aha ngā kōrero ka taea, kāore hoki e taea, te tiki mai i te whakapuru. E tohu ana ngā granule kikorangi i te waikano whakahāora kua whakahāoratia anō, kua mau hoki ki ngā whēkau moroiti. Kāore ēnei e tohu i te katoa o te waikano i te pūtau, kāore e tohu i te rahinga kua whakahekea, ā, kāore e ine i te pānga koiora. Kia mārama ai te take, whāia ngā hipanga e toru: te whakahekenga i te mata, te tūringiringi o te āhua whakaheke, me te whakahāoratanga anō me te mau ki roto.

He rite te whanonga o ngā āhua e rua ki ērā o ngā rāpoi ngota rerekē

He pūnaha mowhiti papatahi te kikorangi metilīni whakahāora, he utanga hiko tōrunga tōna. Ka memeha ki te wai, ka kaha te ngongo i te aho i te takiwā o te 600 ki te 700 nanometers, ā, he kikorangi tōna āhua. Ko te utanga hiko te mea matua. Kāore tētahi rāpoi ngota whai utanga, whai piringa ki te wai, e ngāwari te kuhu mā tētahi kiriuhi lipid, nō reira ko te kupu tūpato i ngā tuhinga pūtaiao he āhua uaua te whakawhiti i te kiriuhi, ehara i te kore rawa e taea.

Ko te kikorangi metilīni whakaheke, e kīia ana ko te kikorangi metilīni leuko, he kore tae, he kore utanga, ā, ka memeha ki te ngako. Tangohia te utanga hiko, ka mutu te kiriuhi te tū hei pakitara. Ka ngāwari te tūringiringi o te rāpoi ngota whakaheke mā te kiriuhi, ā, kia tae ki roto i tētahi wāhanga e kaha ake ana te whakahāora, ka taea te tuku irahiko anō, ka hoki ki te āhua kikorangi, whai utanga, kua mau. Nō reira ko te matū whakaheke-whakahāora o te waikano tōna tikanga kawe hoki. Hurihia te maha o ngā irahiko, ka huri hoki te āhei ki te whakawhiti i te kiriuhi.

Ka ahu mai ngā irahiko mō te hipanga tuatahi i te pūtau tonu. Ka kawe ngā pūtau whāngote i ngā irahiko mā te kiriuhi pūtau, me te neke i ngā taurite whakaheke mai i ngā kaituku o roto ki ngā kaiwhiwhi i te mata. He mahinga noa tēnei mahi whakawhiti i te kiriuhi pūtau, ka kitea i te nuinga o ngā momo pūtau. He rite hoki te whanonga o te whākōkī whakaheke i te mata endothelium e whakahaere ana i ngā waikano thiazine ki ētahi atu, i tētahi āhuatanga tino whai tikanga: ka mahi tonu i te aroaro o te sainaiti me te asaiti, i ngā horopeta e aukati ana i ngā hipanga o muri. Ko taua wehenga te take matua o tēnei kōrero katoa.

I tuatahi te tohatoha ā-wāhanga, ā, i tata tonu tōna whakamārama i te kaponga

I te tau 1929, i pātai a Marian Irwin o te Rockefeller Institute i tētahi pātai māmā ake. Tērā pea ko te urunga o te waikano he tohatoha noa i waenga i te wai me ngā paparanga ngako o te pūtau, ā, ka taea e tētahi paparanga chloroform te whakakapi i aua paparanga ngako i runga i te tēpu taiwhanga. I roto i āna rangahau urunga mā te ine ngongo aho, i ruia ngā wairewa waikano ā-wai me te chloroform, ā, i whakatauritea te matū i neke ki te wāhanga pararopi ki te matū i uru ki ngā pūtau pūkohu ora.

E rua ngā kitenga o taua mahi e tika tonu ana kia āta whakaarohia. Tuatahi, he trimethyl thionine, e kīia ana ināianei ko azure B, kei roto i ngā wairewa kikorangi metilīni arumoni. He tere ake te urunga o taua poke i tō te kikorangi metilīni ake, otirā i te pH kawakore e nui ake ai te āhua pūtake herekore ka memeha ki te lipid. Ko ētahi urunga i whakaarohia he urunga kikorangi metilīni, he urunga kōwhiri kē o te azure B. Tuarua, nā te pH i whakatau te putanga mā tana whakatau i te āhua katote, ā, he nui ake te waikano i uru ki ngā pūtau whara i tō ngā pūtau kāore i whara. Nā ngā whakarea tohatoha me te āhua utanga hiko i whakahaere te matū i ngongo ai te pūnaha horihori me te pūtau ora. Nā te ōritetanga o ngā mea e rua i tautoko te whakaaro he paparanga ehara i te wai kei te paenga pūtau.

He matakite taua tauira mō ngā lipid me te whakakatote, engari kāore i taea te wehewehe i tētahi waikano e tohatoha ana i tōna ake āhua, i tētahi waikano ka panonihia ā-matū i te mata, ka whakawhiti i tētahi āhua rerekē, ā, ka hurihia anō ki tōna āhua tuatahi ki roto. Me whai whakamātautau rerekē mō taua wehewehenga, ā, ka puta taua whakamātautau e whitu tekau tau i muri mai, i te endothelium o te pūkahukahu.

Te whakahekenga ki waho, te mau ki roto

I mahi a Merker me ōna hoa ki ngā pūtau endothelium kua whakatipuria, nō ngā ia toto matua pūkahukahu o te kau. I whakatakotoria e rātou he raupapa hipanga e toru: ka whakahekea te waikano whakahāora i te mata pūtau ki tōna āhua kore tae whai piringa ki te ngako, ka tūringiringi taua āhua whakaheke ki roto, ā, mā te whakahāoratanga anō i roto i te pūtau ka hangaia anō te āhua whakahāora kāore e ngāwari te whakawhiti i te kiriuhi, ka whakaemi ai. Kātahi ka whakamātauria e tā rātou rangahau kaponga thiazine a te endothelium taua raupapa mā te ngana ki te haukoti i ētahi wāhi motuhake.

Ko te taputapu tuatahi ko te ferisainaiti, he kaiwhiwhi irahiko kāore e taea te uru ki te pūtau. Ina whakaheke ngā whākōkī o te mata i te waikano kikorangi ki tōna āhua kore tae ki waho i te pūtau, ka taea e te ferisainaiti te kapo anō i aua irahiko, ka hanga anō i te waikano kikorangi i te wē whakatipu i mua i tōna whakawhitinga. I te wā e nui rawa ana te ferisainaiti (10 micromolar waikano ki te 50 ki te 500 micromolar ferisainaiti), i tata mutu te kaponga waikano. Nō muri noa i te paunga o te ferisainaiti ka tīmata anō te kaponga i tōna tere noa. I whakaatu hoki ngā raraunga tere tauhohenga i taua kōrero mā tētahi atu ara. I ngaro te ferisainaiti i tētahi tere āhua pūmau, e hāngai ana ki tētahi rere whakaheke pūmau i te mata e whāngai ana i tētahi takawaenga ka taea te whakamahi anō. Engari i ngaro te waikano o waho i te pūtau i runga i tētahi ānau taupū i te hekenga o tōna rahinga. Mā te rere pūmau me te rahinga e heke ana e tohu ko te tohu ferisainaiti e whakaatu ana i te whakahekenga haere tonu, ehara i ngā rāpoi ngota waikano e wehe atu ana i te wairewa.

Nā te taputapu tuarua i tango katoa te hipanga whakawhiti. I herea e te rōpū te kikorangi toluidine O, he matū thiazine e tata ana te whanaungatanga, ki tētahi mekameka polyacrylamide nui rawa kia uru ki te pūtau, ahakoa te āhua whakahāora, whakaheke rānei. I whakaheke tonu ngā pūtau i te waikano kua herea. Nō reira kāore te whakahekenga e hiahia kia uru ki roto i te pūtau. Kei te mata te pūnaha mahi, e hono ana rānei ki taua mata mā te hiko.

Kātahi ka puta te wehewehenga i ahu mai ai te taitara o te pepa. I te 2 millimolar, i kaha te sainaiti me te asaiti ki te pēhi i te whakaeminga waikano. I raro hoki i te karu whakarahi, i tata ngaro ngā putunga kikorangi pōuri me ngā putunga waiporoporo e karapoti noa ana i te karihi. Heoi, kāore tētahi o ngā matū aukati e rua i whakaroa i te whakahekenga o waho i te pūtau: i haere tonu te huringa ferisainaiti, kāore i iti iho, ā, i whakahekea tonu te waerau kāore e whakawhiti i te kiriuhi. I muri kē te wāhi aukati i taua hipanga. Nā te sainaiti me te asaiti i aukati te whakahāoratanga anō me te pupuri ki roto i te pūtau, ehara i te whakahekenga i te mata. I tautoko ngā whakamātautau mana oranga i taua whakamāramatanga, nā te mea i pupuri tonu ngā pūtau i tō rātou whākōkī tohu o te wai pūtau, te lactate dehydrogenase, puta noa i ēnei maimoatanga. Nō reira ehara te ngaronga o te kaponga i te paihana noa, i te pakarutanga rānei o te kiriuhi.

E hāngai tonu ana tētahi whakatūpato o te pepa. I noho ngā putunga kikorangi huri noa i te karihi, engari kāore i roto, e hāngai ana ki te whakahāoratanga i roto i ngā whēkau moroiti o te pūtau. Heoi, kāore te rangahau i tautuhi ko ēhea whēkau moroiti. I kīia ētahi tauira ōrite i ētahi atu momo pūtau nō ngā lysosome, ahakoa he iti ngā taunakitanga. Whakaarohia te mau ki roto hei mea kua whakaūngia, engari ko te wāhi tonu hei mea kāore anō kia whakaūngia. Ka taea e ngā kaipānui e whai ana i te ara o ngā irahiko te haere tonu ki te kawe irahiko a ngā mitokōria me te whakahaere whakaheke-whakahāora, me te tirohanga whānui ki te ngongo me te tohatoha e ai ki te ara urunga.

Ehara te whakapuru i te nui o te matū ka tae ki te kiko

E whakaatu ana tētahi rangahau tuatoru i te putanga ina hono tēnei tikanga kaponga ki tētahi inenga koiora. I kitea e Scott me ōna hoa ka here tika te methyl beta cyclodextrin, he huka āhua mowhiti, ki te kikorangi metilīni. Ko te pūmau hononga mō te matatini whakauru kei te takiwā o te 310 per molar, ki te whakatairite ki te 5846 per molar mō te takiruahanga o te waikano. I ngā pūtau fibroblast L929, nā tēnei herenga i aukati te whakapuru pūtau me te whakaongaonga i te kaponga kūhuka. I te rangahau, nā te whakatipu tuatahi me te cyclodextrin i ārai te whakapuru kikorangi, ā, nā te tāpiri i muri mai i whakatere te tangohanga o te tae. I te wehenga atu o te tohu kikorangi ā-aho i ngā pūtau, i heke haere hoki te kawe kūhuka kua whakahohehia, he tino tata te haere ngātahi.

I whakamārama ngā kaituhi i tēnei hononga hei tautoko i tētahi pāhekoheko tika i waenga i te waikano me tētahi pūmua i te ara whakahohe i te kaikawe kūhuka, kaua i tētahi tikanga ahotea whakahāora e roa ana te mau. He whaitake taua whakatau, engari he rohe tōna. Kāore te whakamātautau e whakaingoa i te pūmua, kāore e whakaatu i te herenga ki te kaikawe tonu, ā, kāore te hononga i waenga i te tangohanga tae me te ngaronga pānga e āhei ki te whakakore i ngā ara katoa e takawaengatia ana e te whakaheke-whakahāora.

Ko te akoranga ka mau tonu e pā ana ki te inenga. E tohu ana te whakapuru ā-aho i te waikano ka kitea, kua whakahāoratia, e hono ana ki te pūtau. Kāore rawa e kitea e taua inenga te rahinga whakaheke kore tae, nō reira ka taea tonu e tētahi pūtau kōmā te pupuri i ngā taurite waikano. Ko tētahi pūtau kua kaha te whakapuru e tohu ana i te waikano whakahāora kua mau, kaua i te nui katoa o te matū kua tae ki te kiko, i te rahi rānei o te pānga. Ka hāngai hoki taua whakatūpato ki ngā tauine rahi ake: ko te whakataurite i te whakapuru i waenga i ngā momo pūtau, ko te whakamahi rānei i tētahi wāhanga kiko pōuri hei taunakitanga kua nui ake te matū i tae atu, he whakahoki i te hapa tuatahi o te ipu. He huringa te kaponga e whai ana i te whakahekenga, te tūringiringi, me te whakahāoratanga anō. Ko tētahi whakaahua kotahi o te āhua kikorangi e kite ana i tētahi wāhanga anake o taua huringa. Ka ahu tika mai i tēnei ngā pānga mahi mō te whakapuru me te whakahaere i te taiwhanga, me te whakamārama i ngā kerēme mō te horopeta me te nui o te matū ka tae atu.