Kaha ts'ebetso ea enzyme ea metabolizing ea lithethefatsi e fokotseha butle-butle ka ho lelefatsa nako ea in vitro, mekhoa ea setso ea in vitro metabolism e na le meeli e kang nako e khuts'oane ea ho incubation, phetoho e tlase ea metabolism le moeli o tlase oa ho fumanoa (tekanyo e tlase ea CLint assay ke 2.5 μL /( min 106 cell)), e ke keng ea khona ho tsebahatsa litlhare tsa CLint butle butle.[1]. Ho sa le joalo,hepatocyteLi na le li-enzyme tse ngata tse hlokahalang bakeng sa oxidation, phokotso, hydrolysis le karabelo ea dimerization ha e bapisoa leli-microsome tsa sebete, le litsamaiso tsa in vitro, mefuta e mengata ea lipale e tloaetse ho ntlafatsoa ho ipapisitsoe lehepatocyte tsamaiso le ho tsoela pele ho etsisa tikoloho ea vivo ho lelefatsa ho boloka tšebetso ea enzyme hohepatocytes, le ho lelefatsa nako ea ho incubation ho fana ka monyetla oa ho lekola phetoho e lekaneng ea metabolism ea lithethefatsi tse liehang ho potlakisa metabolism.[1,2].
Ka lebaka la sena, IPHASE, e le moetapele oa li-reagents tsa likokoana-hloko bakeng sa lipatlisiso tsa in vitro, e bile pula-maliboho HepatoMax™ System le HepatoCon™ Media System e thehiloeng thutong ea li-hepatocyte tsa mantlha tse khomarelang le lisele tsa stromal tsa mefuta e sa tšoaneng, ho akarelletsa le batho, monkey, canine, rat, le mouse, joalo-joalo.hepatocytes e le mohlala, 'me litsamaiso ka bobeli li ile tsa thehoa bakeng sa qeto ea mosebetsi le botsitso ba metabolism ea mefuta e itseng ea enzyme le ho eketseha ha boleng ba karabo ea metabolites ea tolbutamide ea lithethefatsi matsatsing a 10 le matsatsi a 7 ho netefatsa litsamaiso. Metabolite e eketsa boleng ba karabo matsatsing a 10 mme ts'ebetso le botsitso ba metabolism ea mefuta e itseng ea enzyme matsatsing a 7 li ne li ikemiselitse ho netefatsa lits'ebetso.
- (1) Mekhoa e 'meli e hlophisitsoeng ea ho netefatsa litlhare ke tse latelang:
IPHASE-HepatoMax™ke sistimi ea setso ea li-hepatocyte tsa mantlha tsa motho tse hatselitsoeng le lisele tsa stromal. Li-hepatocyte tsa mantlha tsa batho li ile tsa tsosolosoa 'me tsa kenngoa ka lisele tsa stromal sebakeng sa HepatoP ™ bakeng sa matsatsi a 3 ho qala tlhahlobo ea tsamaiso ea lithethefatsi,' me metabolism ea lithethefatsi e ne e etsoa ka serum-e sa lefelloeng ea HepatoDo™ medium, e ileng ea tlatsoa feela ka lithethefatsi ntle le ho fetola seaplane. Kakaretso ea lihora tse 4, 72, 168 le 240 ka mor'a tsamaiso ea lithethefatsi, boleng bo ekelitsoeng ba metabolites ea lithethefatsi bo ile ba khethoa bakeng sa tlhahlobo.
IPHASE-HepatoCon™, ka lehlakoreng le leng, ke mokhoa oa ho hlaolela li-hepatocyte tsa mantlha tsa motho tse khomaretsoeng ka har'a HepatoCon™ medium. Ka mor'a ho tsosolosa motho oa pelehepatocytes, tlhahlobo ea tsamaiso ea lithethefatsi e ile ea etsoa ka mor'a matsatsi a 3 a setso ho HepatoCon™ medium feela, 'me nako e latelang ea tsamaiso, tsamaiso ea setso le mokhoa oa ho hlahloba li ne li tšoana le tsa HepatoMax ™ system.
Ho sa le joalo, ho etsa bonnete ba ho nepahala le ho tiea ha liphetho, IPHASE e entse taolo e mahareng (sele- mahala) le taolo ea lisele tsa stromal ka nako e le 'ngoe, ka lipehelo tse tharo, mme liphetho li bonts'a horeIPHASE-HepatoMax™ leIPHASE-HepatoCon™ litsamaiso li hlahisitse karabelo e matla ea tlhōrō ea metabolite ho tloha ka letsatsi la 3 ho ea pele, le hore bobeli ba bona ba bonts'a sekhahla se matla sa phetoho ea metabolic.
- (2) Metabolism ea lithethefatsi e itšetlehile haholo ka hepatocyteCYP450enzyme, mme ts'ebetso ea eona e ka lekanyetsoa ho hlahlojoa hantle.
TheIPHASE-HepatoMax™ leIPHASE-HepatoCon™ litsamaiso li na le ts'ebetso e ntle.
IPHASE e thehile mekhahlelo e mene ea taolo e mahareng (ha ho na lisele), HepatoMax™, HepatoCon™ le lisele tsa stromal. Ho sebelisa lebota-motho ea ka sehloohong ea khomarelanghepatocytes e le mohlala, metabolite e eketsa litekanyetso tsaCYP1A2, CYP2B6leCYP3A4li netefalitsoe ka letsatsi la 0, 3 le 7 kamora moohepatocyteho hlaphoheloa ka matsatsi a 3 ho sebelisa finasteride, bupropion le midazolam e le li-substrates, ka ho latellana. Litekanyetso tsa keketseho ea metabolite li bontšitse hore bobeliIPHASE-HepatoMax™ leIPHASE-HepatoCon™ litsamaiso li bonts'itse ts'ebetso ea enzyme e sebetsang ka letsatsi la 7, e ntse e khothaletsa metabolism e tloaelehileng ea lithethefatsi.
- (3) Ntle le netefatso ea ts'ebetso ea enzyme, botsitso bo botle ba metabolic hape ke mohato oa bohlokoa le oa bohlokoa ho netefatsa ts'ebeliso ea mefuta ea in vitro.
IPHASE e thehile mekhahlelo e meraro ea HepatoMax™, HepatoCon™ le lisele tsa stromal ho fumana botsitso ba metabolic ea Tolbutimide nakong ea lihora tse 80 ho sebelisa mohlala oa li-hepatocyte tsa mantlha tsa motho e le mohlala, tse ileng tsa tsamaisoa matsatsi a 3 ka mor'a ho tsosolosoa ha litho tsa mantlha.hepatocytes, 'me liphetho li bontšitse hore bobeli baIPHASE-HepatoMax™ leIPHASE-HepatoCon™ Litsamaiso ka bobeli li bonts'a ts'ebetso e matla ea ho tlosa metabolism ka har'a boleng bo bolelele ba nako ea tlhahlobo.
Ka kakaretso, IPHASE, joalo ka moetapele oa in vitro bio-reagents, e ntlafalitseIPHASE HepatoMax™ leIPHASE HepatoCon™ in vitro mehlala e thehiloeng leboteng-e sebelisitsoeng motho oa mantlha, tšoene, canine, rat le toebahepatocytes le lisele tsa stromal tsa mefuta e fapaneng, tse nang le phetoho e ntle haholo ea metabolism, mesebetsi e sebetsang ea li-enzyme le mesebetsi e matla ea ho hlakola metabolism, e fanang ka khetho e ncha bakeng sa bareki ba rona ho etsa litlhare tse tlase, 'me ke balekane ba bohlokoa ho hlokomela ho sibolloa ha lithethefatsi! TheIPHASE HepatoMax™ leIPHASE HepatoCon™ mefuta ea in vitro e fana ka litefiso tse ntle haholo tsa phetoho ea metabolic, mesebetsi e sebetsang ea enzyme le mesebetsi e matla ea ho hlakola metabolism, e fanang ka likhetho tse ncha bakeng sa bareki ho hlahisa lithethefatsi tse tlase-ho hlakola, mme ke molekane oa bohlokoa ho sibolloeng ha lithethefatsi!
Referense:
[1]阮婷婷,鞠武建,熊海伟,等.低清除率药物的代谢稳定性预测模型研究进中展展[J]. 2019(2):152-160.
[2] Di L, Trapa P, Obach R S, et al. Mokhoa oa ho fetisoa oa nova bakeng sa ho fumana boleng bo tlase-bo hloekisitsoeng[J]. Metabolism ea lithethefatsi le sebopeho, 2012, 40(9): 1860-1865.
Nako ea poso: 2024-07-19 17:20:41