Li-Hepatocytes tsa ho lla

I. Selelekela

Ts'ebetsong ea lithethefatsi le ea moamoheli oa ho sebelisa lithethefatsi le ho etsa lipatlisiso tsa menoana ho hlahloba karolo ea bohlokoa ho hlahloba metabolism le polokeho ea batho ba bangata ba neng ba phalla. Har'a bona,li-hepatocytes tse hlakileng mmeLibaka tsa ho emisoa Sebeletsa mesebetsi e fapaneng, e etsang khetho e pakeng tsa tsona e bohlokoa bakeng sa lithuto tsa vitro. Ho utloisisa liphapang litabeng tsa bona le likopo li ka thusa bafuputsi ba khetha mokhoa o loketseng ka litlhoko tsa bona tse khethehileng.

Li-bioscients tsa iphase, Moetapele oa ho hlapolla lintho tsa khale, o tšehetsa tsoelo-pele ea mahlale ka ho fana ka Phahameng ea PEST - Hepatocytes ea boleng bakeng sa lits'ebetso tsa lipatlisiso. Ka boiphihlelo ka botsebi ka seleng - Sehlopha sa rona se thehiloe, sehlopha sa rona se tiisa hore lefatše la ho fumanoa le ka boleloang ho etsa se hlokahalang ho etsa se hlokahalang.

Sengoliloeng sena se hlahloba phapang ea bohlokoa lipakeng tsa lintoa tsa boiketsetso le ho emisoa, likopo tsa tsona tse lekantsoeng tsa lithethefatsi, le joang ho khetha mofuta o nepahetseng bakeng sa lipatlisiso tsa hau.

II. Litoro tse futhumatsang tse potelletseng ke eng?

Li-hepatocytes tsa li-opagh ke li-mobolayers tsa ho hokahanya le ho etsa li-monolayers, li etsa hore li tšoanele nako e telele - nako lithutong tsa vitro.

Litšobotsi tsa Bohlokoa:

• E khona ho latela lipolaiti tsa moetlo

Boloka sebete - Mesebetsi e tobileng ea nako e telele ho feta linako tse telele

E loketse ho ithuta ho ikoetlisa, chefo le tšebetso ea lipalangoang

Likopo tsa tlhahlobo ea lithethefatsi:

• Long - Lintlha tsa Thupelo ea Li-Metabolism tsa Metabolism:Tloaetse ho hlahloba hore na lingaka li sebetse joang ha nako e ntse e feta.

• Lithuto tsa Marato ea Anzyme:Ho lekola hore na lithethefatsi li susumelletsa mesebetsi ea sebete ea Severyme.

• Tlhahlobo ea hepatotoxic:Ho tsebahatsa tšenyo e ka bang teng e bakiloeng ke metsoako e mecha.

• Patlisiso ea ts'ebetso ea Tsamaiso:Ho ithuta sefifi sa lithethefatsi - Tšebelisano ea lithethefatsi le metsamao ea hepatic / efflux ea efflux.

III. Ke lintho life tse emisitsoeng ke liphiri?

Lits'ireletso tsa ho emisoa ke ha lisele lisele tse khabisitsoeng bakeng sa mantlha bakeng sa ho khutsufatsa - Ba boloka tšebetso ea enzymatic empa ba sa hokahane le lipolanete tsa moetlo, ba li etsa tse sebetsang bakeng sa liteko tse potlakileng.

Litšobotsi tsa Bohlokoa:

• Batho bao ba sa kopaneleng, ba bolokiloeng naheng ea ho emisoa

• E loketseng ho khuts'oane - Nomoro ea lithethefatsi ea lithethefatsi

• Fana ka karolo e tšepahalang ea I le prose ea ii enzyme ea boithabiso
  
  

Likopo tsa tlhahlobo ea lithethefatsi:

• Bokhutšoanyane - Ithute lithuto tsa lithethefatsi tsa metabolism:Ho lekanya litefiso tsa tumello ea li-vis tsa kalafo.

• Phahameng - Ho kena ho Screeting (HTS):Ho leka kapele metsoako e mengata bakeng sa botsitso ba metabolic.

• Reaction Phenotyping:Ho Khetholla Barababobo ba Enzyme ba ne ba kenyelletsa metabolism ea lithethefatsi.

• Lithethefatsi - Thuto ea Lieo-Burractions:Ho lekola metaolism le bokhoni ba enkizyme.

IV. Phapang ea Bohlokoa pakeng tsa lithaelese tse hlakileng le tse emisang

Liphapang tsena li totobatsa bohlokoa ba ho khetha mofuta o nepahetseng oa ho khetha mofuta o nepahetseng oa ho ithuta ka sepheo sa ho ithuta.

V. Likopo tsa tlhahlobo ea lithethefatsi le lipatlisiso

Litopo tsa tikatices tse hlakileng le tse emisang li sebelisoa hohle ho lipatlisiso tsa pharmaconetic le tse ngata. Ho utloisisa likopo tsa bona ho netefatsa moralo o tiileng oa liteko.

2. Likoloi tsa lithethefatsi le phabello ea lithethefatsi (DMPK):

• Litulo tse hlakileng tsa hepatocytes li tšehetsa nako e telele - lithuto tsa ho tsitsa tsa metabolic tsa metabolic.

• Li-tipacytes tsa ho emisoa ho etsa tlhahlobo e potlakileng ea litsela tsa metabolic.
  
  

To defnopology le hepatoxicity Concking:

• Litulo tse hlakileng tsa hepatocytes li khona ho fumana lithethefatsi tse sa sebetseng - kotsi e khahlehileng ea sebete (Dili).

• Likhau tsa ho emisoa ha lits'oaetso li lekola mokhoa o phollatsi oa cytotoxicity le karabelo ea metabolic.
  
  

Phao I & Phase Ithuma Makaboolism oa Metabolism:

• Phase seo ke se etsang (oxidation, phokotso) li hlahlojoa ka nepo u sebelisa mefuta ka bobeli.

• Lithuto tsa mekhachang tsa karolo (Glucuronidation, sulfation hangata li hloka li-apticytes tse hlakileng tse hlakileng.
  
  

Boikoetliso le lithuto tsa thibelo:

• Li-hepatocytes tse hlakileng li bohlokoa bakeng sa Lipatlisiso tsa Cyp enzyme tsa MaratorMe.

• Litoro tsa ho emisoa ho fana ka leseli le potlakileng ho bokhoni ba enzyme.
  
  

Phahameng - Ho kenya tlhahlobo ea lithethefatsi:

• Li-Ipatocytes tsa ho emisoa li nolofalletsa ho le leholo - Screengs Screengs.

• Li-hepatocytes li khona ho thusa lithutong tse qaqileng tsa melaetsa.

VI. Mokhoa oa ho khetha mofuta o nepahetseng oa Hepatocyte bakeng sa lipatlisiso tsa hau

Ha o khetha Ipatocytes bakeng sa lipatlisiso, ho lokela ho ithutoa lintlha tse 'maloa:

Ho ithuta nako:

• Nako e telele - liteko li hloka li-apatocytes tse hlakileng.

• Bokhutšoanyane - metabolism a mananeo a rata ho rata limpho tsa lipelaelo.
  
  

Lipakane tsa Teko:

• Boiketsi, chefo le lithuto tsa liparanta:Li-hepatocytes.

• Ho hlahlojoa ha Metabolism le thibelo ea li-assays:Li-tikatoctes tsa ho emisoa.
  
  

Khetho ea Mefuta:

• Hupatocytes ea Bathobakeng sa tokollo ea bongaka.

• Liphoofolo tsa liphoofolo tsa liphoofolobakeng sa lithuto tsa pelehi.
  
  

Li-hetpatocytes tse ntle tse nchafatsang:

• Lithabetso tse ncha tsa hepatocytese boloka e tiile, empa e na le ho fumaneha ha chelete e fokolang.

• Li-hepatocytes tsa "hepatocytesFana ka mokhoa o bonolo le tlhahiso.
  
  

Li-bioscients tsa iphase li fana PER PUP - Lintoa tse phahameng tsa boleng le ho emisoa bakeng sa lits'ebetso tsa lipatlisiso. Bophahamo ba rona ba netefatsa hore bo-rasaense ba amohela botsitso le ba netefalitsoeng ea koetliso ea likopo tsa koetliso ea ho sibolloa hoa li sibolla le tlhahlobo ea polokeho.

VII. Sephetho

Ho utloisisa liphapang lipakeng tsa li-attetocytes tsa li-apatetocytes le tikpectrictes ea ho emisoa ho bohlokoa bakeng sa ho khetha mofuta o motle bakeng sa lithuto tsa tlhahlobo ea lithethefatsi le tse fapaneng. Litulo tse hlakileng tse ipatileng li ipatela nako e telele -

Iphase Bignices, mofani ea ts'episelitsoeng - Lithaba - Litharo tsa Phetoho ea Hepatocyte - Lipatlisiso tsa Maxicology. Ka li-cappabut tse ngata R & D le marang-rang a tsamaiso ea lefatše, re netefatsa hore bo-rasaense ba fihlella mefuta e tšepahalang bakeng sa ho itšeha - Patlisiso ea Zet.

Bakeng sa tlhaiso-leseling e batsi mabapi le ho khetha li-Ipatocytes tse nepahetseng bakeng sa lipatlisiso tsa hau tsa lipatlisiso, etela li-bisycients tsa Iphas kajeno.