Te kahurangi methylene me te multiple sclerosis: ngā mea i whakamātauria e te rangahau kararehe

Ki te rapu koe i te kahurangi methylene mō te MS, ka kitea ngā pepa e āhua whakautu ana i te pātai kotahi. Engari he rerekē ngā pātai. I hoatu e tētahi rangahau te kahurangi methylene ki ngā kiore māuiui hei maimoatanga. Kāore tērā atu i whakamahi hei maimoatanga mō tētahi kararehe. I whakamahia te kahurangi methylene hei whakapoke kahurangi i ngā tapahanga angiangi o te ua tuaiwi, kia kitea ai e te mātanga mātai mate te myelin mā te karu whakarahi.

Koinei te ariā matua o tēnei tuhinga katoa. E rua ngā whakamahinga o tēnei waikano i te koiora, ā, ko te pounamu anake te mea e ōrite ana. Ina whakamātauria hei rongoā pea, ka hoatu he horopeta ki tētahi kararehe ora, ā, ko te pātai mēnā ka rerekē te mate. Ina whakamahia hei whakapoke, ka pania ki te kiko mate kua whakapūmautia i muri i te whakamātautau, ā, ko te pātai he pēhea te āhua o te kiko. Ki te kore koe e kite i taua rerekētanga, ka pānui koe i tētahi wāhanga tikanga mātai mate me te mea nei he putanga maimoatanga.

He aha te EAE, mā ngā kupu māmā

Ko te experimental autoimmune encephalomyelitis, e whakapotohia ana ki te EAE, he tauira kararehe e whakamahia whānuitia ana mō ētahi āhuatanga o te multiple sclerosis. Ka whakaoho tētahi kairangahau i te pūnaha ārai mate o tētahi kiore whakaraerae mā tētahi wāhanga pūmua myelin me tētahi matū kaha hei whakapakari i te urupare ārai mate. Kātahi ka whakaeke te pūnaha ārai mate i te pūnaha io matua o te kararehe ake. Ka tīmata te ngoikore i te wāhanga whakararo o te kiore, ka piki whakarunga, ā, he māmā te whakawhiwhi kaute i runga i tētahi tauine 0 ki te 5, mai i te hiku tāwerewere ki te pararutiki o ngā waewae o muri.

Nā te māmā o taua whakawhiwhi kaute ka whakamahia nuitia te EAE, engari koia anō tētahi take e whakapohehe ai. Ka puta noa ake te MS ki te tangata, he whānui ake, he iti ake hoki te mārama o ngā whāinga o te whakaeke ārai mate, ā, ka puta ngā tohumate e pā ana ki te kite, te rongo ā-tinana, te hinengaro, te roro tuarongo, me te nekeneke, i roto i ngā wā e hoki mai ai te mate, e ahu whakamua tonu ai rānei. Ka whakaputaina anō e te EAE ētahi tukanga kua kōwhiria, pērā i te mumura, te ngaronga myelin, me te wharanga axon, i raro i ngā āhuatanga kua whakahaerehia. Kāore e whakaputa i te MS hei mate iti noa iho. Ka taea e ngā kaipānui e hiahia ana ki te anga whānui te arotake i ngā whakaaro mō te mahi a te kahurangi methylene i te taumata pūtau, i mua i te whakatau mō tētahi kerēme mate takitahi.

I whakamahia hoki e ngā pepa e rua i raro nei ngā antigen EAE rerekē, ā, he mea whai take tēnei. I whakaaweawehia e te rangahau maimoatanga te mate mā te MOG35-55, he peptide poto nō te myelin oligodendrocyte glycoprotein. I whakaaweawehia e te rangahau mātai mate te mate mā te MP4, he whakakotahitanga o ngā wāhanga o te myelin basic protein me te proteolipid protein. Ka rerekē ngā wāhi e puta ai ngā wharanga me te whanonga o te mumura i runga i te kāwai kiore me te antigen kua kōwhiria. Nō reira, ehara ēnei rangahau e rua i te whakahaere rua i te whakamātautau kotahi.

Te mahere: mai i te tauira ki te pātai ki ngā herenga

Me waiho tēnei ripanga kia tuwhera. Koinei te tohutoro matua mō tēnei tuhinga. E whakaatu ana ia rārangi ko tēhea pātai haumanu ka taea e te tauira te tirotiro, he aha tonu i inea, me te wāhi e mutu ai te taea te whakamahi i ngā kitenga ki te tangata.

Ka taea e te tangata e arowhai ana i te kupu matua o te rongo kōrero e whai ake nei te whakamahi anō i aua tīwae, mā te āwhina o te pānui rangahau i mua i ngā whakamātautau haumanu: pātaihia te momo kararehe me te antigen, te whakamahinga o te pūhui, ngā putanga i inea, mehemea hoki e whakaatu ana te hua i te haere o te mate, i te āhua rānei o te kiko i tētahi wā kotahi.

Te putanga maimoatanga: ngā mea i rerekē nā te hoatutanga horopeta

I whakamahia e te rangahau maimoatanga o 2016 i te Journal of Neuroimmunology ngā kiore uwha C57BL/6, e 8 ki te 10 wiki pea te pakeke, i whakaohohia ō rātou pūnaha ārai mate mā te 250 micrograms o te MOG35-55 mō ia kiore. Whai muri i te whakaaweawe i te mate, i tohaina matapōkeretia ngā kararehe EAE ki tētahi rōpū kahurangi methylene, ki tētahi rōpū EAE kāore i whiwhi maimoatanga rānei, ā, i aroturukihia ngā kaute haumanu tae noa ki te rā 30 pea.

He iti iho ngā kaute haumanu o ngā kiore i whiwhi maimoatanga i ō ngā kiore whakataurite EAE mai i te rā 15 ki te rā 30, ā, he whai tikanga ā-tatauranga taua rerekētanga, me te P iti iho i te 0.01. I tautoko hoki te tātari ua tuaiwi i taua kitenga: he iti ake te kuhu o ngā pūtau mumura, te ngaronga myelin, me te ngaronga axon ki ngā kararehe i whiwhi maimoatanga.

Ko te āhuatanga motuhake ko te huinga inenga tuku tohu. Nā te maimoatanga i piki ai te whakahohe AMPK me te whakapuaki SIRT1, ā, i pehia te whakahohe NF-kB, he whakakā matua mō te mumura. I te taha o te ārai mate urutau, i whakaitihia te urupare Th17, ā, i whakapakaritia te urupare Treg. Nō reira, ko te raupapa e whakaarohia ana: te kahurangi methylene, kātahi ko te AMPK me te SIRT1, kātahi ko te hekenga o te tuku tohu NF-kB, kātahi ko te nekehanga mai i te Th17 whakaawe mumura ki te Treg whakahaere urupare, kātahi ko te wharanga kiko māmā ake, kātahi ko ngā kaute iti iho.

He whakamāramatanga taua raupapa, ehara i te raupapa take me te hua kua whakamātauhia. E whakaatu ana te rangahau i te rongoā, ngā rerekētanga tohu, me te pai haere o te mate e neke tahi ana. Kāore e whakamātau ana nā te AMPK me te SIRT1 te painga katoa. Waihoki, kāore te tuhinga kua whakarārangitia tūmatanuitia e whakaatu mārama ana i te horopeta tika i te milligram mō ia kilogram, te ara tuku, te rā tīmata, te roanga rānei, kia taea ai te tārua i te hōtaka maimoatanga mai i te whakarāpopototanga anake. Me whakaaro he mea kāore anō kia manatoko tētahi tau horopeta e whakahuatia ana mō tēnei pepa i tētahi whārangi hoko, ki te kore e tohutoro ki ngā tikanga i roto i te tuhinga katoa. Ko te kohinga taunakitanga whānui ake mō te kahurangi methylene ki te tangata te wāhi hei tirotiro mēnā i whanake tēnei kitenga tōmua mō te ārai mate hei raraunga haumanu.

Te putanga mātai mate: ngā mea i whakaaturia e te kiko i roto i te ono marama

I whakamahia e te rangahau MP4 o 2015 i PLoS ONE ngā kiore uwha C57BL/6, i whakaohohia ō rātou pūnaha ārai mate mā te 200 micrograms o te MP4 i roto i te complete Freund adjuvant, me te tāpiri i te tāoke pertussis i te rā o taua whakaoho me te 48 hāora i muri mai. Kāore tētahi kararehe i whiwhi kahurangi methylene hei rongoā. Whai muri i te whakapūmau me te whakatō i te kiko ki tētahi matū tautoko, i whakapokea ngā tapahanga whakawhiti o te ua tuaiwi, kotahi micrometer te mātotoru, ki te kahurangi methylene mō te tirohanga mā te karu whakarahi māramatanga. I whakamahia hoki te karu whakarahi irahiko ki te ara io o mua me te taha, kia kitea ai ngā taipitopito iti ake.

I tīpakohia te kiko i ngā wāhanga e toru: i te tihi o te wā whakapeka, e 7 ngā kiore; i te toru marama i muri i te tīmatanga, e 5 ngā kiore; ā, i te ono marama i muri i te tīmatanga, e 10 ngā kiore. He āhua ōrite ngā kaute haumanu toharite i aua wāhanga, e tata ana ki te 1.7 ki te 1.8 i runga i te tauine 0 ki te 5. He rerekē te kōrero a te kiko. I piki te wharanga myelin anake mai i te 569,000 muka pea mō ia millimeter pūrua i te tihi whakapeka ki te 1,496,000 pea i te ono marama. He whai tikanga ā-tatauranga te whakataurite i te wā whakapeka ki te wā roa, me te P ōrite ki te 0.027. I tata rearua te wharanga myelin me te wharanga axon e pā tahi ana i te ono marama. I noho iho ngā muka e hanga myelin anō ana i te kotahi ōrau i ia wāhanga, he taipitopito e whakaiti ana i te tūmanako mō te whakaora kiko.

I whai te wharanga axon i tētahi tauira āhua U: he nui i te tihi whakapeka, he iti ake i te toru marama, ā, ko te taumata nui rawa i te ono marama. I whai hononga taua wharanga ki te pupuhi o ngā mitochondria me te hekenga o te tawhiti i waenga i ngā neurofilament. Kāore ngā kaitātari i mōhio ki te kaute me te wāhanga o ia tauira kiko. E whakapakari ana tēnei i te whakamāramatanga kāore ngā kaute haumanu i tino whakaatu i te wharanga hanganga e haere tonu ana.

Ko taua rerekētanga te tino takoha o te rangahau ki te kaipānui e whai ana i te MS. Kāore te pūmautanga o te kaute hauātanga i tohu he pūmau hoki te kiko. E whakaatu ana hoki he aha tēnei pepa e kore ai e tautoko i tētahi kerēme maimoatanga mō te kahurangi methylene me te MS. Ko te wā te mea i whakamātauria, ehara i te maimoatanga.

He aha e kore ai tētahi o ēnei rangahau e whakaū i te painga ki ngā tūroro

Whakaarohia ia pepa he mea e pai ana te whakautu i tētahi pātai whāiti, engari kāore rawa e whakautu i te pātai mō ngā tūroro.

Tuatahi, he rerekē te take o te mate. Ka āta whakaaweawehia te EAE mā tētahi antigen kua tautuhia me tētahi matū whakapakari urupare ārai mate. Ka whanake noa ake te MS ki te tangata, me tētahi huinga urupare ārai mate whānui ake, tae atu ki ngā pūtau T, ngā pūtau B, te ārai mate taketake, me ngā pūtau glia e noho ana i te kiko. Kāore e taea te whakapae ka whakarerekē tētahi pūhui i taua urupare whānui ake ki te tangata nā te mea ka whakarerekē i tētahi urupare e anga nui ana ki te MOG i te kiore.

Tuarua, he rerekē ngā āhuatanga e kitea ana. He inenga māmā te ngoikore e piki ana mai i te hiku ki ngā waewae o muri o te kiore. Ka kōpeke i ngā āhuatanga huhua o te MS ki te tangata ki tētahi tau kotahi mō te nekeneke. He maha ngā wā ka whakarerekē ngā rongoā i ngā kaute EAE wā poto, engari kāore e whakarerekē i te haere o te mate ki te tangata. Nā reira, he taputapu te EAE mō te tātari tuatahi me te tirotiro tukanga, ehara i te whare haumanu iti.

Tuatoru, kāore anō kia whakatauria te nui o te pānga ki te rongoā me te wā tuku. He rerekē te tuku horopeta haere tonu mai i te tīmatanga o tētahi whakamātautau kiore e 30 rā i te whakamahi mā te waha mō te wā roa a tētahi tangata kua tau kē te mate. Kāore hoki tētahi o ngā rangahau i ine i ngā taumata rongoā i te pūnaha io. Ki te kore taua hononga, kāore he tūāpapa hei whakawhiti mai i tētahi kukū i runga i te pereti taiwhanga, i tētahi horopeta ki te kiore rānei, ki tētahi hōtaka maimoatanga mō te tangata.

Tuawhā, kāore ngā pepa e rua e tārua ana i ngā kitenga o tētahi ki tētahi. He rerekē ngā antigen, ngā pātai, ngā putanga i inea, ā, i tētahi rangahau kāore rawa he maimoatanga. He hapa whakarōpū te whakahua tahi i ēnei hei rangahau e rua e whakaatu ana i te painga o te maimoatanga MS.

Te tikanga o ēnei kitenga mō ngā kaipānui e paunatia ana ngā taunakitanga

Kāore he kawa kahurangi methylene mō te MS kua whakaūngia i roto i ēnei pepa. E tautoko ana te rangahau maimoatanga i te rangahau anō mō te AMPK, te SIRT1, te NF-kB, me te taurite o Th17 ki Treg i te MOG EAE. He whakamaharatanga te rangahau mātai mate ka taea e te wharanga kiko te ahu whakamua ahakoa e āhua pūmau ana ngā kaute, ā, i ētahi wā ko te kahurangi methylene i tētahi wāhanga tikanga he ipu whakapoke kē, kaua he rongoā. Me maumahara ngā kaipānui e whai ana i te rangahau multiple sclerosis e haere tonu ana ki taua rerekētanga o te whakapoke me te rongoā. Me kōrero ki tētahi mātanga haumanu mō ngā pātai haumaru, tae atu ki ngā tūraru e pā ana ki te toto me ngā pāhekoheko rongoā, me te titiro hoki ki ngā raraunga haumaru whānui mō te kahurangi methylene, i mua i te mahi a te tangata i runga i ngā kupu matua o ngā rongo taiwhanga.

Ka taea te whakatakoto i te whakatau matua ki te rerenga kotahi. I hoatu e tētahi rangahau i whakahuatia he horopeta kahurangi methylene ki ngā kiore MOG EAE, ā, i pūrongo he māmā ake te mate me tētahi nekehanga o te ārai mate e whakaiti ana i te mumura, engari kāore tērā atu rangahau i hoatu horopeta, ā, i whakamahi i te kahurangi methylene hei whakapoke ua tuaiwi anake i a ia e tuhi ana i te whakaeminga o te wharanga myelin me te wharanga axon mō te ono marama, nō reira kāore ēnei rangahau e rua e whakaū ana ka āwhina te kahurangi methylene i te MS ki te tangata.