MITOXONDRIALIY-REDOKS-IMMUN O'QI: SKELET MUSKULASI VA QON TOMORI DISFUNKSIYASINI BAG'LAYDIGAN INTEGRATIV MOLEKULYAR MEXANIZM
DOI:
https://doi.org/10.37547/Keywords:
Mitoxondrial disfunksiya; Oksidlovchi stress; Immun hujayra polarizatsiyasi; Skelet mushak miopatiyasi; Endotelial disfunksiya; Periferik arteriya kasalligi; Redoks signalizatsiyasi; Mitofagiya; Uremik toksinlar; Yallig'lanish.Abstract
So'nggi o'n yillikdagi tadqiqotlar mitoxondriyalarning energiya ishlab chiqarishdan tashqari, hujayra signalizatsiyasi va taqdirini belgilashda muhim rol o'ynashini ochib berdi. Ushbu maqola skelet mushaklari va qon tomir disfunktsiyasi o'rtasidagi patofiziologik bog'liqlikni tushuntiruvchi integrativ molekulyar mexanizm sifatida "mitoxondrial–redoks–immun aksi" kontseptsiyasini ilgari suradi. Mitoxondriyal elektron transport zanjiridagi nosozliklar nafaqat energiya tanqisligiga, balki reaktiv kislorod turlarining (ROS) nazoratsiz ishlab chiqarilishiga ham olib keladi. Ushbu redoks muvozanatining buzilishi yallig'lanish hujayralari, xususan makrofaglar va T-limfotsitlarning funksional polarizatsiyasini o'zgartirib, surunkali past darajadagi yallig'lanishni keltirib chiqaradi. Periferik arteriya kasalligi (PAD), surunkali buyrak kasalligi (CKD) va yurak yetishmovchiligi (HF) kabi patologiyalarda mitoxondrial disfunksiya, oksidlovchi stress va immun hujayralar faollashuvining o'zaro ta'siri natijasida skelet mushaklarining atrofiyasi, qisqarish qobiliyatining pasayishi va endotelial disfunksiya rivojlanadi. Yangi multiomik tadqiqotlar, xususan, uremik toksinlarning (kynurenin, indoksil sulfat) mitoxondrial genlar ekspressiyasini bostirishi va mushak kuchsizligiga olib kelishi aniqlandi. Shu bilan birga, immun hujayralaridagi mitoxondrial dinamika (masalan, Drp1 oqsili sulfenillanishi) va redoks-sezgir signal yo'llari (cGMP-PKG, NAMPT-NAD+) ishemik sharoitda qon tomir regeneratsiyasi va mushaklarning tiklanishida hal qiluvchi ahamiyatga ega. Mazkur aksning molekulyar tarkibiy qismlarini aniqlash, skelet mushaklari va qon tomir tizimining o'zaro bog'liq kasalliklarini davolash uchun mitoxondriyal transplantatsiya, antioksidant strategiyalar va immunomodulyatsiyani o'z ichiga olgan yangi terapevtik yondashuvlarning rivojlanishiga zamin yaratadi.
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