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Microsomemes: Ba ratoang ho Vitra Metabolic mohlala bakeng sa lipatlisiso tse seng tsa lithethefatsi

Microsomemes: Ba ratoang ho Vitra Metabolic mohlala bakeng sa lipatlisiso tse seng tsa lithethefatsi

Microsomemes: Tlhaloso le mesebetsi

Maemong a mangata, Microsomemes e bua ka mekhabiso ea dinomi, Vesikular Mefuta e tlase ea 100, e thehiloeng ka bophara ba thepa ea enddopperation (er) nakong ea homonenization ea sele homogenization le e fapaneng. Tsena li likopanyo tse phahameng tse phahameng tse fetisisang ho etsa likarolo tse peli tsa bohlokoa: er membasomes le li-ribosomes. Haholo-holo li-Microchrome p450 (cyp450) li-enzolism tsa muvolism 'me ke enzolistion ea ho phekola metabolism ea metabolism ea metabolism.

Vitra, likokomehemes le boloka tšebetso ea bohlokoa tsa ER, ho kenyelletsa protein Synthesis, Proptingo Gitcosytherhes, Mefuta ea VoSynthes le Lipething.

 

Mohloli oa Tissiamo

Mefuta ea

Ho panya

Sebete

Motho, Cynomolgus Monkey, Rhesus monkey, Ntja ea Begle, Rat, Mouse, Khauta hamster, Feline, Minipig, Bovine, Khoho, Guinea pig, Litlhapi, leLinku.

0.5ml, 20mg / ml

Mala a mala(Pmf)

Motho, Cynomolgus Monkey, Rithes Monkey,Ntja ea Begle, Rat, Mouse, Hamster ea khauta,Minipig.

0.15ml, 10mg / ml

0.5ml, 10mg / ml

Mala a mala(PMSF - MAHALA)

Motho,Cynomolgus Monkey, Rithes Monkey,Ntja ea Begle, Rat, Mouse, Harger, Milipig.

0.15ml, 10mg / ml

0.5ml, 10mg / ml

Liphio

Motho, Cynomolgus Monkey, Rhesus monkey, Ntja ea Begle, Rat, Mouse, Minipig.

0.5ml, 10mg / ml

Lung

Motho, Cynomolgus Monkey, Rhesus monkey, Ntja ea Begle, Rat, Mouse, Minipig.

0.5ml, 10mg / ml

Setšoantšo sa 1: Microsomemes (mohloli: inthanete)

  1. Li-organs tsa senotlolo sa metabolism ea lithethefatsi

Metabolism oa lithethefatsi e bua ka lik'hemik'hale tse fetolang lithethefatsi ka har'a 'mele, ho fella ka sebopeho sa sebopeho. Ts'ebetso ena, hape e boetse e tsejoa e le biotransformation, haholo-holo e etsahala litho tsa litho tsa Bole, haholo-holo li-organs tse kang sebete, liphio, matšoafo, mala, mala. Har'a bana, sebete ke sebaka se ka sehloohong sa metabolism, se lateloang ke liphio e le setho sa bobeli sa bohlokoahali.

Ka har'a sebete, sethethefatsi - Cababoname ea ts'ebetso ea ts'ebetso e ka khetholloang maemong a mabeli: karolo Ke metabolism.

  • Phase ke metabolism (Karolo eo ke fanang ka eona): Karolo ena e kenyelletsa lekhabunyane le amanang le ho hlahisa lihlahisoa tse bohareng, hangata ho kenyeletsoa lihlopha tsa elektrolip tsa motlakase le oksijene. Boitšoaro bona bo ka lebisa ho HEPATHOTOXY.
  • Phase II Metabolism (Phase Ii Reaction): Mokha ona o na le karabelo ea tumellano, o sebeletsa ho hlakola lithethefatsi. Kamora metabolism, lithethefatsi tse ngata li lahleheloa ke mosebetsi oa limela, leha ba fokolang ba ka ba mahlahahlaha a mafolofolo a phepelo.

Ka sebete, sebete se sebetsana ka hoo e ka bang 70% - 80% ea metabolism kaofela, e hatisa karolo ea eona ea mantlha ho biotransformation.

Ntle le sebete, liphio li kenya letsoho ho metabolism ea lithethefatsi, e sebetsang bakeng sa 10% - 20% ea mesebetsi e felletseng ea metabolic. Liphio li ile tsa phatlalatsa boitšoaro bo botle le metabokono ba bona ka ho fetoha le ho fetoha ha ho fifala le secreri. Leha ho le joalo, bokhoni ba bona ba ho sebelisa litlhare ho na le meeli e fokolang, bo ka lebisang ho bokelloang lithethefatsi tse itseng le khang e ka bang khang e ka bang teng.

Ntle le sebete le liphio, litho tse ling tse kang ho anyesa lithethefatsi, ho abosa le metabolism, ho ea fihla boholo ba lithethefatsi.

Setšoantšo sa 2: Boitšoaro bo Hloetse ke Monooxgease (mohloli: inthanete)

  1. Li-enzymes tsa senotlolo ka har'a metaboli ea lithethefatsi

Joalokaha ho tšohliloe, metabolism ea lithethefatsi hangata e latela ts'ebetso e fapaneng ea litsamaiso tse fapaneng tsa enzyme tse fapaneng ka sebete, liphio, gastrointestinanse le litho tse ling. Ho utloisisa lipapatso tsa enzearic tsa litho tsena ho bohlokoa bakeng sa thuto e felletseng ea lits'ebetso tsa metabolism tsa metabolism.

Li-enzymes tsa lipalesa hangata li aroloa litlelaseng tse peli: litsamaiso tsa minosal litsamaiso le litsamaiso tsa enzsal.

  • Litsamaiso tsa Minomal Enzyme:
    Li-enzyme tsena li rekisoa haholo ka har'a litho tsa liporophilic tsa pherekano ea endoplasmic ka lisele tsa sebete le lisele tse ling. Sehlopha sa bohlokoa ka ho fetisisa sa li-enzyme tse ntle ho hepatic Microsos microsomers tse kopaneng - Tsamaiso ea oxidase ea oxidase e tsejoang e le monooxese. Li-enzyme tsena li emela tsela ea mantlha bakeng sa metabolism ea lithethefatsi 'meleng, e khona ho nka mokhoa o fapaneng le oxi oxidation. Ts'ebetso ea biotranformation ke li-enzyme tsena e hloka hore cytochrome P450 (Cyp450), lifofane tsa masole
    Ntle le moo, UDP - Glusunusyltransferansferasferasferasferasferasesferasesferasesferases ea mantlha
  • Not - Litsamaiso tsa enzyal enzyal:
    Hape e tsejoang e le enzyme ilika, li kenyelletsa li-uggengs, sulfransferasferansferasferasferasferasferasferansferasferasferasferasferasferasferasferas. SENDO YA METSOALLE E MOLEMO OA KOTSI EA K'ONA II

Ntle le karolo ea eona ea 'mele ho boloka metsi le tekano ea Balecrolyte le lintho tse khahlisang tsa motlakase le tse makatsang, le tsona li na le setho sa bohlokoa sa bokhabane.

  • Karol i metabolism ho liphio:
    E kenyeletsa li-enzyme tsa P450, tse nang le dehydroseline, le meabo ea libuoni tsa tsona e tlase haholo ho feta ba sebete, ke liphio ke sa buseha.
  • Phase, Metabolismm In The Liphio:
    Haholo-holo o kenyelletsa ho nyahlatsa litho, li-cass, nats, le li-amino acid tse kopanyang li-enzgicating, li bapala karolo e kholo metabolism ea lithethefatsi.

Kameho, e le e 'ngoe ea litho tsa maoto tse kholohali, li boetse li bapala karolo ea bohlokoa lipakeng tsa lithethefatsi. Ka pampitšana e meholo ka ho fetisisa, lithethefatsi tse ngata li etsa qeto e matlafatsang ho feta metabolao ho feta metabolao. Mekhoa ena ea metabolic e etsahala ka litsela tse peli:

  1. Enzzlism ea enzymatic nakong ea lisele tse linyebe tsa mala, tse kenyelletsang li-enzyme tse kang cyp450, li-ugg450, li-uggs le Lipises.
  2. Metabolism e ikhethang ea metabolism ka microbiota ea mala.

Ka bobeli, sistimi ena ea enzzyatic e fapaneng e tiisa metabolism e sebetsang le ho hlophiseha ha lithethefatsi, tse totobatsang ho rarahana le mekhoa ea metabolism ea metabolism 'meleng.



Leha ho le joalo, ka tsoelo-pele e tsoelang pele ea moriana, ho sebelisa litlhare tse khaphatsehileng ho ruile bocha lilemong tsa morao tjena ka potlako, ho qala ho feta pele - fetela metabolism. Ho se na lithethefatsi tse tloaelehileng, ho na le mekhoa e mefetloang e fana ka meriana ka kotloloho mehahlanong ea pulmonari, e qoba ho tsosa pele - Litlaleho tsa Tsopelo. Sena se totobatsa bohlokoa ba ho etsa lipatlisiso ka har'a metabolism ka har'a matšoafong a lifokoana-hloko.

Matšoafo a na le mefuta e fapaneng ea lithethefatsi - Enzyme ea metabole, ho kenyeletsa le li-h450, li-hyzzise tsa hydrogas, le lipalesa - e nang le monooxes. Har'a bana, purimary P450 barezymes ba bapala karolo ea tšoaetso ea ho senya lijo tsa Xenobios

Ka kakaretso,Metabolism ka tloaelo 'meleng hangata ke ts'ebetso e hokahaneng e kenyelletsang lits'ebetso tse ngata le litsamaiso tsa enzyme. Kahoo, nakong ea ho khetha lithethefatsi tse seng tsa khale, ho khetha mekhoa ea vitro ho bohlokoa ho feta metabolic le ho khetholla enzyme ea bohlokoa.

 

  1. Mefuta ea metabolism ea vitro ea metabolism: Microsomemes

Ha ho bapisoa le lithuto tsa vivollism tsa vivolilism, tse tsoang ho vitro tsa vitroro li fokotsa ho kenella ka ho toba le lithibelo tse lipakeng tsa lithethefatsi le li-enzyme. Ka lebaka leo, ho mefuta ea vitra Metabolismmm e fetohile khetho e khethiloeng nakong ea nts'etsopele ea lithethefatsi. Mefuta e tloaelehileng ea lithunya tsa vitro, Metabolism ea lithethefatsi li kenyelletsa Microsomes, S9 fucktions, S9 Fuoa hore sebete ke sebaka sa mantlha sa metabolism ea lithethefatsi, lisele tsa hePatic le likarolo tsa bona tsa subclund-tse kang sebete tsa sebete tsa sebete, liver s9-Na mehlala ea mantlha ea ho ithuta metabolism ea lithethefatsi.

Microsomemes, ka ho khetheha, na Membrar membrar membrar e tsoa ho setumo sa pheletso sa FragerPlerop Thatdoprop's Li abeloa li-organs tse kang sebete, liphio, mala, mats'oafo a matšoafo. Joalokaha li-Microsomemes ke li-enzymes tse kang cytochrome p450 (cyp450) le lipehelo, li fumana litsela tse ngata tsa lithethefatsi tsa metabolis. Kahoo, ho khetha lisele - MICSOMES e tobileng ke mohato oa bohlokoa oa ho sebelisa vitro ea vitro nalliolism ea metabolism.

Ho feta moo, ho latela litataiso tsa teknoloji bakeng sa lithuto tsa morao-rao tsa pharmacokinetic tse kang litoeba, likolobe tsa Guinea, le litšoene li sebelisoa hangata. Bakeng sa lithethefatsi tse ncha, bonyane mefuta e 'meli e lokela ho sebelisoa,' me e le litoeba le e 'ngoe eo e seng hape - ea Roden U feta Mefuta ea Liphoofolo, lisebelisoa tsa bathojoalo ka Microsomes ea sebete-e boetse e hatisoa e le lisebelisoa tsa bohlokoa bakeng sa lithuto tse seng tsa addminical. Ka lebaka leo, ho khetha Microsomes ho tsoa mefuta e mengata, ho kenyelletsa le batho, ke ho nahanisisa ka poliotal lipatlisisong tsa lithethefatsi tsa metabolism.



Ka lebaka la sena,Iphase, e le mofani ea etellang pele oa linko tsa vitro-kougengs, ho kenyelletsa le mefuta e mengata ea mefuta e mengata ea mefuta e mengata ea mefuta e mengata ea mefuta e fapaneng ea mefuta e mengata ea mefuta e mengata ea mefuta e mengata, ho kenyeletsoa le batho, litšoene, lintja le litoeba. Lihlahisoa tsena li fana ka likhetho tse ngata bakeng sa liphapang tsa mefuta ea mefuta ea limela, botsitso ba metabolic, le metabolition ea Metabolic, le Metabolic enzyme Phenolity.

Ka mehato ea taolo ea boleng bo thata, Iphase o tiisa hore ba tšepahala, ba thusa bareki Boloka nako le ho ntlafatsa katleho. Li-Microsomes tsa Iphase ke khetho e loketseng ea lipatlisiso tsa vitra.

Melemo ea lihlahisoa tsa iphase ea iphase:

  • Ho latela:Li-seswe tsohle tse sebelisitsoeng ho tlhahiso li entsoe ka liteishene tse netefalitsoeng ka ho ts'oara botsitso.
  • Ts'ireletso:Lithane tsa tlhahiso li lekoa bakeng sa likokoana-hloko ho netefatsa boleng ba sehlahisoa le polokeho.
  • Boleng bo phahameng:Lihlahisoa tse tsamaeang ka thata tsa boleng ba kahare, li netefatsa hore boholo bo boholo ba sehlopha sa batch se na le boholo ba batch.
  • TLHOKOMELISO:Lihlahisoa tse ntle tsa likoti ho tsoa ho mefuta ea likokoana-hloko kapa lisele lia fumaneha ho kopana le litlhoko tse ikhethang tsa bareki.

Lilemo tse ngata tsa R & D tsa boiphihlelo,Iphasee qalile ho le phahameng - Qetetsa ea ho etsa lipatlisiso tse ngata ho feta masimong a mangata le mekhahlelo e mengata. Lihlahisoa tsena li sebeletsa e le lisebelisoa tsa bohlokoa tsa pele - nts'etsopele ea lithethefatsi, mekhoa le mekhoa ea ho hlahloba mahlale a bophelo. Ba boetse ba fana ka tharollo e loketseng bakeng sa lithuto tsa sebopeho sa liphatsa tsa lefutso lijong tsa lijo, meriana le lik'hamera.

Re ikemiselitse ho tšehetsa bafuputsi ka lihlahisoa tsa rona tse ncha le tse tšepahalang!



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