Te puru metilīni me te ate momona: ngā kitenga o ngā rangahau whakamātau

He ingoa kotahi te ate momona mō ētahi raruraru rerekē. Ki tētahi tangata, ko te pūtake he kaha tonu te inu waipiro mō te wā roa. Ki tētahi atu, ko te nui rawa o ngā matūkai, me te ātete ki te insulin me te nui ake o te ngako ka tukuna ki te ate. Mā te karu whārahi pea e kitea ai te penapena ngako noa i ngā āhuatanga e rua, engari he rerekē ngā pūtake o mua. Mā taua rerekētanga e whakatau he aha ngā mea ka taea e tētahi whakamātau te whakaū.

He iti ngā tuhinga rangahau mō te puru metilīni me te ate momona, ā, mō tēnei pātai, kei te taumata i mua i ngā whakamātau ki te tangata katoa. E toru ngā rangahau kiore nunui me ngā kiore iti e tino whakahuahia ana, ā, kāore e ōrite te aronga o ā rātou kitenga. Nā tētahi rangahau whāngai ethanol i whakatika tētahi panonitanga redox, engari kāore i huri te ngako o te ate. Nā tētahi rangahau kai ngako-nui i whakaheke te ngako o te ate, me te panoni hoki o ngā tohu whakahaere. I kitea e tētahi rangahau kararehe hauora ngā putanga tauaro mō te whakahāoratanga peroxy o ngā lipid i te ate me te tākihi. Ina pānuitia ngātahitia, ka kitea he aha me wehe tonu ēnei putanga e toru: te panoni redox, te whakahohe tohu whakahaere, me te whakaeminga ngako ki te kiko.

E toru ngā putanga he ngāwari te whakapohehe

Ka whakaahua tētahi inenga redox i te whakahaere irahiko. Ko te ōwehenga NAD+ ki NADH o te ate e tohu ana mēnā kei te āhua whakahāoratia, whakahekea rānei te taiao o te pūtau. Mā te whakahāora ethanol e huri ai te NAD+ hei NADH, nō reira ka heke taua ōwehenga i te inu waipiro mō te wā roa. Ka taea e tētahi waikano tango irahiko te whakapiki anō. He tukanga matū tēnā, ehara i te taunakitanga kua iti iho te ngako e penapenahia ana.

Ka whakaahua tētahi inenga tohu i te whakahaere. He whākōkī whakahaere te SIRT1 e whakawhirinaki ana ki te NAD+, e whakarerekē ana i ngā pūmua whai wāhi ki te mahi a ngā mitochondria me te whakahaere lipid. Ko te AMPK he pūoko mō te pūngao iti; ina whakahohea, ka tautoko i te whakahāoratanga wahie, ka aukati hoki i te hanga lipid. Ina pūrongotia e tētahi tuhinga te whakahohe SIRT1 i te ate nā te puru metilīni, kei te pūrongo taua tuhinga i tētahi panonitanga whakahaere. Kāore anō kia pūrongotia he putanga mō tētahi tūroro.

Ka whakaahua tētahi inenga mātai kiko, matū koiora rānei i te ate tonu. Ko ētahi tauira noa ko te nui o te triglyceride mō ia karamu kiko, te tae Oil Red O o te ngako kūpapa, te aromatawai hematoxylin me te eosin i te pupuhi ā-poihau me te wharanga, me te mahi ALT i te wē toto. Mā tēnei kāwai tuatoru anake e whakautu mēnā i pai ake te whakaeminga ngako ki te ate nā te puru metilīni i taua whakamātau.

Mā te wehe i ēnei kāwai e ārai ai te hē o te whakamāramatanga e tino kitea ana: kāore te putanga pai mō te redox, mō ngā tohu whakahaere rānei e ōrite ki te iti iho o te ngako o te ate.

Tauira ethanol: i whakatikaina te redox, kāore i huri te ngako

Ko te kitenga tōraro tino mārama nō tētahi rangahau whāngai ethanol mō te wā roa ki ngā kiore nunui Wistar tāne. I whiwhi ngā kararehe i te ethanol hei wāhanga o tētahi kai wai, ka piki ki te 36 ōrau o te pūngao katoa. I whiwhi ngā kararehe whakataurite i te rahinga kai ōrite, me te kūhuka hei whakakapi i te pūngao ethanol. I whiwhi hoki tētahi rōpū ethanol me tētahi rōpū whakataurite i te puru metilīni, 130 mg mō ia rita kai, arā, tata ki te 42 mg mō ia kg i ia rā, mai i te rā 5 ki te rā 30.

I whakatau tatahia te āhua redox mā ngā takirua hua pākia paerewa: te lactate ki te pyruvate mō te cytosol, me te 3-hydroxybutyrate ki te acetoacetate mō ngā mitochondria. I te tīmatanga o te whāngai ethanol nui, i kitea ngā panonitanga nui i ngā rōpū ethanol: i heke te ōwehenga NAD+ ki NADH i te cytosol tata ki te 62 ōrau, ā, i ngā mitochondria tata ki te 71 ōrau, me te piki hoki o te glycerol 3-phosphate. Nā te puru metilīni i whakahoki te nuinga o aua panonitanga, ā, i whakahoki te glycerol 3-phosphate kia tata ki ngā uara whakataurite, me te kore e huri i te nui o te ethanol i kainga, te pikinga taumaha o te tinana, te ethanol rānei i te serum.

He rerekē tā te ngako o te ate i whakaatu ai. I te rā 12, i mua i te whakaeminga nui o te ngako, kāore he rerekētanga o te triglyceride i waenga i ngā rōpū. I te rā 27, he nui ngā pikinga triglyceride i ngā rōpū ethanol, ahakoa te puru metilīni. I te rā 30, i piki te lipid katoa tata ki te 89 ōrau, me te triglyceride tata ki te 196 ōrau, i ngā kararehe whāngai ethanol; kāore anō i pāngia ēnei e te waikano. He ōrite te āhua o te whakaeminga ngako i waenganui o ngā wāhanga iti o te ate, ahakoa i hoatu te matū, kāore rānei. Ko tā ngā kaituhi whakatau, ehara te panonitanga redox nā te ethanol i te pūtake matua o te ate momona i muri i te whāngai mō te wā roa i tēnei tauira. He āwhina i konei te ako ki te wehe i te āhua e hāngai ai ngā kitenga kararehe me ngā kitenga pūtau ki te tūraru tangata: tērā pea he tūturu tētahi tukanga, engari kāore tonu e whakahaere i te putanga.

Koinei te rangahau hei whakahua ina kī tētahi me tango katoa te ngako o te ate i te whakatikanga redox. Kāore i pērā i tēnei hoahoa whakamātau.

Tauira pākia: ngā tohu whakahaere me te iti iho o te ngako, i ngā kiore iti

He rerekē te āhua ka puta i tētahi rangahau pūtau ate me ngā kiore iti whāngai kai ngako-nui i aro ki te SIRT1 me te AMPK. I ngā pūtau HepG2, ngā pūtau AML-12, me ngā pūtau ate tuatahi nō ngā kiore nunui, nā te puru metilīni i whakapiki te ōwehenga NAD+ ki NADH, i whakapiki te pūmua SIRT1, i whakaheke te tāpiringa rōpū acetyl ki te kaiwhakahaere PGC-1alpha, i whakapiki te nui o te DNA mitochondrial me te whakamahinga hāora, ā, i whakahohe i te AMPK, me ngā pikinga whai muri o te CPT-1 me te PPARalpha. Ina whakaitihia te whakaaturanga o SIRT1, ka ngaro te whakahohe AMPK; ka herea te mekameka tukanga ki te SIRT1 i taua pūnaha pūtau. I whakahē hoki te waikano i ngā tohu hanga ngako nā te kaiwhakahohe LXR T0901317 me te pānga o te palmitate, tae atu ki te whakaoho SREBP-1c, FAS, me ACC.

I te wāhanga kararehe, i whakamahia ngā kiore iti C57BL/6 tāne, i whāngaihia ki tētahi kai e 60 ōrau te ngako mō te 8 wiki. I hoatu te puru metilīni mā te waha e whā ngā wā i ia wiki i ngā 4 wiki whakamutunga, ki te 3, ki te 10 mg rānei mō ia kg i ia rā. Ki ngā kiore i whiwhi i te matū, he iti iho te tae Oil Red O, he iti iho te triglyceride o te ate, he iti iho te pupuhi ā-poihau me te paheketanga ngako i te mātai kiko, ā, he iti iho te ALT i te wē toto i ō ngā kiore kai ngako-nui kāore i whiwhi i te matū. I ngā mahi mātai nekeneke rongoā i taua tuhinga anō, i kitea te wātea koiora mā te waha tata ki te 31 ki te 35 ōrau, me te ngongo tata katoa mai i te whēkau, engari he nui te whakarerekētanga mā te pākia. I te ate hoki te ōwehenga kiko ki te wē toto teitei rawa; nō reira, i runga i te tohatoha o te matū, he whaitake pea te pānga ki te ate.

He tohu tūturu tēnei o te whakaiti i te whakaeminga ngako, engari he whāiti ōna rohe. He whakamātau poto ki ngā kiore iti, me te 9 ki te 10 kararehe i ia rōpū, kotahi te momo kai, e rua ngā rahinga matū, me ngā wiki e whā o te hoatutanga. Ka whakamātau i ngā āhuatanga o te whakaeminga ngako nā te pākia me te mumura o te ate whai ngako, ehara i te mate e pā ana ki te waipiro. Kāore hoki e whakamātau i te cirrhosis, te whakahokinga o te fibrosis, i tētahi putanga tangata rānei. Ko te mahi a ngā inenga mitochondrial me te redox i te whakamāramatanga o ēnei putanga, he tohu kei te tautoko i tētahi whakapae, ehara i te tohu mō tētahi rahinga matū, tikanga whakahaere rānei.

He tirohanga poto ki te kiko hauora: kotahi te rahinga, he tauaro ngā whēkau

He rangahau tuatoru e whakamahia nuitia ana hei tautoko i ngā kerēme mō te ate, ahakoa kāore e tika kia whakamahia pērā. I tētahi whakamātau 30 rā ki ngā kiore nunui Wistar uwha hauora, e rima ngā kararehe i whiwhi i te puru metilīni 1 mM i roto i te wai inu, ā, e rima hei rōpū whakataurite. Kāore te superoxide dismutase, te catalase, me te glutathione kua whakahekea i huri i te ate, i te tākihi rānei. I piki paku te whakahāoratanga peroxy o ngā lipid i te ate, ā, i heke i te tākihi. I heke te ALT me te creatinine i te serum, me te kore panoni o te hauota urea o te toto.

Ko te whakamāramatanga tika he rerekē ngā pānga i ia momo kiko o ngā kararehe hauora, ehara i te maimoatanga mate. I taua pānga matū kotahi, he paku tautoko i te whakahāoratanga tā tētahi tohu i whakaatu ai i te ate, ā, he paku whakamarumaru tā taua tohu anō i whakaatu ai i te tākihi, i te wā kāore ngā pūnaha ārai whakahāoratanga paerewa i huri. Nā te tokorima noa o ngā kararehe i ia rōpū me te kore tauira mate, he whakatūpato tēnei tuhinga kia kaua e kī he matū ārai whakahāoratanga whānui mō te ate te puru metilīni. Ka whakaatu hoki he aha me whai horopaki mate kua tautuhia ngā panonitanga whākōkī ate i mua i te kī he whakapainga aua panonitanga.

Te whakataurite i ngā whakamātau ate e toru

Mā te ripanga e kitea ai te kōrero matua. He waikano puru rite, engari he rerekē te koiora. Ka wehe te rangahau ethanol i te angitu redox i te kore angitu mō te ngako. Ka whakakotahi te rangahau kai i ngā tohu whakahaere me te whakapainga ngako i roto i te tauira kotahi. Ka whakaatu te rangahau kararehe hauora ka taea ngā tohu redox te neke ki ngā aronga tauaro i ngā whēkau rerekē.

He aha e kore ai e puta he kerēme maimoatanga

Kāore tētahi o ēnei rangahau i whakauru i te tangata whai ate momona. He rerekē ngā rahinga matū, ngā ara hoatu, me ngā roanga i waenga i ngā tuhinga, ā, kāore e taea te huri hei tikanga mō te tangata mā te whakarahi, te whakaiti noa rānei i runga i te rahinga tinana. Nā te tokoiti o ngā rōpū, otirā ko ngā kararehe e toru mō ia wā inenga redox i te rangahau ethanol me ngā kararehe e rima mō ia rōpū i te rangahau kararehe hauora, he nui tonu te rangirua. He rerekē hoki te ira, te kāwai kararehe, te hanganga kai, me te wā hoatu matū e pā ana ki te wharanga. Ā, e whakaatu ana ngā tauira mate e rua i ngā pūtake rerekē o mua, nō reira kāore e taea e te putanga pai o te rangahau kai te whakatika te putanga tōraro o te rangahau ethanol, kāore hoki e taea te mahi whakamuri.

Mō te tangata kua whakatauria he mate ate tōna, ko te pānuitanga whai take ake ko te tūpato, ehara i te maimoatanga. Ka whakamārama te tirohanga whānui ki ngā tūpato tākihi me te ate mō te puru metilīni he aha ka panoni ai ngā pātai haumaru i te ngoikoretanga o te whēkau, ahakoa he pai te āhua o tētahi tuhinga kararehe. Kawea te whakatau mate, ngā hua taiwhanga o nā tata nei, te hua tika me te ara hoatu, me te rārangi rongoā katoa ki tētahi mātanga haumanu. Pātai atu he aha ngā taunakitanga e tautoko ana i taua hua mō taua kaupapa ki tētahi tangata he pēnei te nui o tōna ngoikoretanga.

Hei whakakapi: i panoni te puru metilīni i te āhua redox o te ate i tētahi tauira ethanol, me te kore e whakaiti i te ngako e penapenahia ana; i whakahohe i te SIRT1 me te AMPK me te whakaiti i te ngako i tētahi tauira pākia kiore iti; ā, i whakaatu i ngā pānga redox motuhake ki ia whēkau i ngā kiore nunui hauora. He huinga aronga ēnei mō te rangahau, ehara i te maimoatanga kua whakaūngia mō te ate momona.