{"id":3843,"date":"2024-08-03T08:19:59","date_gmt":"2024-08-03T08:19:59","guid":{"rendered":"https:\/\/longchangextracts.com\/?p=3843"},"modified":"2024-08-03T08:19:59","modified_gmt":"2024-08-03T08:19:59","slug":"astragaloside-iv","status":"publish","type":"post","link":"https:\/\/longchangextracts.com\/da\/astragalosid-iv\/","title":{"rendered":"Beskyttende effekt af astragalosid IV p\u00e5 h\u00f8jdosis S-ketamin-induceret PC12-celleskade"},"content":{"rendered":"

Beskyttende effekt af astragalosid IV p\u00e5 h\u00f8jdosis S-ketamin-induceret PC12-celleskade
\nMillioner af sp\u00e6db\u00f8rn og sm\u00e5b\u00f8rn verden over f\u00e5r hvert \u00e5r generel an\u00e6stesi. Talrige unders\u00f8gelser har vist, at enkeltst\u00e5ende og kortvarige an\u00e6stesier ikke har negative virkninger p\u00e5 nervesystemets udvikling, men h\u00f8je doser eller gentagen eksponering for an\u00e6stesimidler kan for\u00e5rsage kognitiv dysfunktion og neurologiske udviklingsforstyrrelser. An\u00e6stesimidlers indvirkning p\u00e5 hjernens udvikling har tiltrukket sig stor opm\u00e6rksomhed fra mange for\u00e6ldre.<\/p>\n

S-ketamin (SK) er S-enantiomeren af ketamin og blev officielt godkendt af FDA som et adjuverende l\u00e6gemiddel til behandling af sv\u00e6r depression i 2019. Det er ogs\u00e5 et almindeligt anvendt bed\u00f8velsesmiddel i p\u00e6diatriske og obstetriske operationer. Det er bekymrende, at folk tilsyneladende kun er interesserede i at studere dets antidepressive virkninger uden at v\u00e6re s\u00e6rlig opm\u00e6rksomme p\u00e5 de potentielle risici, det kan medf\u00f8re. En nylig unders\u00f8gelse analyserede 962 bivirkninger relateret til SK og fandt, at kvindelige patienter, patienter, der fik h\u00f8jdosis SK, og patienter, der fik flere l\u00e6gemiddelbehandlinger, havde st\u00f8rre sandsynlighed for at opleve bivirkninger. Derfor er det af stor betydning at udforske mekanismen for SK-induceret nerveskade og finde tilsvarende h\u00e5ndteringsforanstaltninger for b\u00e5de sp\u00e6dbarns- og voksenan\u00e6stesi.
\nAstragalosid IV (ASIV) er en af de vigtigste aktive ingredienser, der er isoleret fra den traditionelle kinesiske medicin Astragalus membranaceus. Unders\u00f8gelser har vist, at det har en lang r\u00e6kke farmakologiske virkninger, herunder anti-tumor, anti-inflammatorisk, antioxidant, anti-fibrotisk og anti-apoptotisk virkning. Desuden har det vist sig at v\u00e6re et naturligt neurobeskyttende middel. Der er dog kun f\u00e5 rapporter om, hvorvidt ASIV kan lindre nerveskader for\u00e5rsaget af an\u00e6stesimidler. Derfor valgte denne unders\u00f8gelse den almindeligt anvendte neurale cellelinje rotte binyref\u00e6okromocytomceller, nemlig PC12-celler, til at konstruere en in vitro-skademodel af SK, udforske den neurobeskyttende effekt af ASIV og give reference til rationel brug af SK og udvikling af nye l\u00e6gemidler til ASIV.<\/p>\n

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\nAn\u00e6stesimidlers neurotoksicitet har altid v\u00e6ret en bekymring for det internationale samfund. US Food and Drug Administration og International Association for the Study of Anesthesiology holdt et f\u00e6lles m\u00f8de for at diskutere vigtigheden af at standardisere pr\u00e6klinisk forskning og etablere rapporteringsstandarder for an\u00e6stesiinduceret perinatal neurotoksicitet, og foreslog brugen af nye metoder til at l\u00f8se nogle af de st\u00f8rste problemer p\u00e5 dette omr\u00e5de. Hvad ang\u00e5r ketamin, er det i mods\u00e6tning til de fleste an\u00e6stetika en NMDA-receptorantagonist. Medicinsk blokade af NMDA-receptorer kan \u00e6ndre den excitatoriske h\u00e6mningsbalance, der er n\u00f8dvendig for hjernens udvikling, og f\u00f8re til neurotoksicitet. Unders\u00f8gelser har vist, at ketamin kan fremkalde neurotoksicitet hos mennesker gennem den mitokondrielle apoptosevej p\u00e5 en tids- og dosisafh\u00e6ngig m\u00e5de, mens dets enantiomer S-ketamin ikke er blevet rapporteret til at fremkalde lignende bivirkninger. Derfor spekuleres der i, at n\u00e5r en vis koncentrationst\u00e6rskel er n\u00e5et, kan SK ogs\u00e5 aktivere den mitokondrielle apoptosevej og for\u00e5rsage celleapoptose.
\nMitokondrier, som er centrum for cellul\u00e6r metabolisme og den vigtigste regulator af redoxbalancen, spiller en afg\u00f8rende rolle i forekomsten og udviklingen af sygdomme. Blandt de mange fysiologiske reaktioner, der medieres af mitokondrier, er oxidativ stress en af n\u00f8glefaktorerne i aktiveringen af den mitokondrielle apoptosevej, og overdreven ROS er det materielle grundlag for forekomsten af oxidativ stress. Almindeligt anvendte an\u00e6stetika i klinisk praksis har vist sig at fremme eller reducere graden af oxidativ stress. For eksempel kan inhalationsan\u00e6stesi sevofluran fremkalde neuronal apoptose ved at \u00f8ge den intracellul\u00e6re Ca2+-koncentration, h\u00e6ve ROS-niveauerne og \u00f8ge ekspressionen af mitokondrie-apoptosevej-relaterede proteiner Cleaved-Caspase-9, Cytochrome C og Bax\/Bcl-2. Lokalbed\u00f8velsesmidlet bupivacain aktiverer ROS-medieret autofagi, hvilket f\u00f8rer til nedsat autofagi-flux og nedsat cellelevedygtighed. Brugen af reaktive oxygenarter kan dog vende denne autofagiske skade betydeligt. I den mitokondrielle vej f\u00f8rer stigningen i ROS-indhold til \u00e6ndringer i de relative ekspressionsniveauer af Bax og Bcl-2. Bax aktiveres og oligomeriseres ved mitokondriernes ydre membran og binder sig derefter til specifikke molekyler for at \u00e6ndre mitokondriernes membranpermeabilitet. Cytokrom C frigives derfor fra mitokondrierne til cytoplasmaet, hvor det bindes til faktorer som Apaf-1 for at danne apoptotiske legemer og aktivere Pro-Caspase-9 til spaltning. Den spaltede Caspase-9 aktiverer yderligere downstream-relaterede apoptotiske faktorer og fremmer celleapoptose.<\/p>\n

Astragalosid IV er et naturligt aktivt stof med st\u00e6rke antioxidantegenskaber, og forskning har vist, at nogle af dets virkninger er t\u00e6t forbundet med mitokondrier. For eksempel kan ASIV fremme mitokondriel autofagi, reducere ophobningen af beskadigede mitokondrier og dannelsen af mitokondrielle reaktive oxygenarter. Liu et al. fandt ogs\u00e5 ud af, at ASIV kan ud\u00f8ve neurobeskyttende effekter ved at angribe alfa-synuclein, et protein, der er placeret i mitokondriernes indre membran og er st\u00e6rkt udtrykt i den menneskelige hjerne. Man kan se, at ASIV har potentiale til at behandle nerveskader for\u00e5rsaget af bed\u00f8velsesmidler.
\nBaseret p\u00e5 ovenst\u00e5ende forskningsresultater og analyser udf\u00f8rte denne unders\u00f8gelse et in vitro-eksperiment ved hj\u00e6lp af den mitokondrielle apoptosevej som en ledetr\u00e5d til at behandle h\u00f8jdosis SK-induceret nerveskade med ASIV. De endelige eksperimentelle koncentrationer af SK og ASIV blev bestemt til at v\u00e6re henholdsvis 450 \u03bc g\/mL og 25 \u03bc mol\/L ved hj\u00e6lp af CCK-8-assay. Derudover viste eksperimentet, at PC12-celler, der blev udsat for h\u00f8je doser SK, ikke kun viste en signifikant stigning i apoptosehastighed og ROS-indhold, men ogs\u00e5 aktiverede de vigtigste upstream-molekyler Bax, Bcl-2, Caspase-9 og Cytochrome C i den mitokondrielle apoptosevej. Dette indikerer, at h\u00f8jdosis SK inducerer apoptose i PC12-celler ved at aktivere den ROS-medierede mitokondrielle apoptosevej. Efter behandling med ASIV blev disse \u00e6ndringer induceret af SK signifikant h\u00e6mmet, hvilket viser, at ASIV har en vis beskyttende virkning p\u00e5 PC12-celler under denne proces.
\nSammenfattende kan astragalosid IV lindre h\u00f8jdosis S-ketamin-induceret skade i PC12-celler, og dens mekanisme kan v\u00e6re relateret til h\u00e6mning af mitokondriel apoptosevej.<\/p>","protected":false},"excerpt":{"rendered":"

Beskyttende effekt af astragalosid IV p\u00e5 h\u00f8jdosis S-ketamin-induceret PC12-celleskade Millioner af sp\u00e6db\u00f8rn og sm\u00e5b\u00f8rn verden over f\u00e5r hvert \u00e5r generel an\u00e6stesi. Talrige unders\u00f8gelser har vist, at enkeltst\u00e5ende og kortvarig an\u00e6stesi ikke har negative virkninger p\u00e5 udviklingen af nervesystemet, men h\u00f8je doser eller gentagen eksponering for an\u00e6stesimidler kan [...].<\/p>","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[20],"tags":[],"yoast_head":"\nProtective effect of Astragaloside IV on high-dose S-ketamine induced PC12 cell injury - China Chemical Manufacturer<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/longchangextracts.com\/da\/astragalosid-iv\/\" \/>\n<meta property=\"og:locale\" content=\"da_DK\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Protective effect of Astragaloside IV on high-dose S-ketamine induced PC12 cell injury - China Chemical Manufacturer\" \/>\n<meta property=\"og:description\" content=\"Protective effect of Astragaloside IV on high-dose S-ketamine induced PC12 cell injury Millions of infants and young children worldwide receive general anesthesia every year. 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