NHP Non-Alcoholic Steatohepatitis (NASH) Model

Tshawb nrhiav Western noj zaub mov ntxias NASH: nrog cov rog rog, Kev noj zaub mov siab Fructose (HFFD) rau 8 lub lis piam.Closer Metabolic thiab Liver Pathphysiology Zoo sib xws, Ntau Cov Kab Mob Muaj Feem Ntau, Txhim Kho Cov Qauv Qauv, Kev Kho Mob Txhais Kev Kho Mob thiab Cov Txheej Txheem

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Tsis-Alcoholic Steatohepatitis (NASH)yog ib hom mob hnyav ntawm cov kab mob uas tsis yog-alcoholic fatty siab (NAFLD) uas tshwm sim los ntawm kev sib sau ntawm cov rog hauv daim siab, nrog rau kev mob thiab daim siab cell puas. Tsis zoo li daim siab rog yooj yim, NASH cuam tshuam txog kev raug mob hepatocyte thiab fibrosis, uas tuaj yeem ua rau mob hnyav dua xws li cirrhosis, daim siab tsis ua haujlwm, thiab mob qog nqaij hlav hepatocellular. NASH yog sib txuas nrogmetabolic syndromes , suav nrog kev rog rog, ntshav qab zib hom 2, dyslipidemia, thiab kub siab, ua rau nws muaj kev txhawj xeeb txog kev noj qab haus huv rau pej xeem vim nws muaj peev xwm ua rau lub siab tsis zoo thiab nws qhov ntau ntxiv thoob ntiaj teb.

Ua rau:Qhov laj thawj tiag tiag ntawm NASH tsis nkag siab tag nrho, tab sis nws ntseeg tau tias yog los ntawm kev sib xyaw ntawm cov noob caj noob ces, metabolic, thiab ib puag ncig.Insulin tsis kam , uas feem ntau nrog kev rog rog thiab ntshav qab zib hom 2, ua lub luag haujlwm tseem ceeb hauv kev txhim kho NASH los ntawm kev txhawb nqa cov tsub zuj zuj ntawm fatty acids hauv daim siab. Qhov no rog buildup ua rau oxidative kev nyuaj siab thiab o, ua rau daim siab cell puas. Ntxiv yam xws li dyslipidemia, plab microbiota hloov, thiab inflammatory cytokines ntxiv exacerbate lub siab raug mob. Genetic predispositions, suav nrog cov kev hloov pauv hauv cov noob xws li PNPLA3, kuj ua rau muaj kev loj hlob thiab kev loj hlob ntawm NASH. Cov yam ntxwv ntawm kev ua neej, suav nrog kev noj zaub mov tsis zoo thiab kev coj tus cwj pwm tsis zoo, yog qhov tseem ceeb rau kev cuam tshuam ntawm metabolic uas cuam tshuam rau tus kab mob.

Kev kuaj mob NASH feem ntau suav nrog kev tshawb fawb txog kev kuaj pom, kuaj lub siab ua haujlwm, thiab qee zaum daim siab biopsy los ntsuas qhov mob thiab fibrosis. Muab nws qhov xwm txheej asymptomatic nyob rau theem pib, ntau qhov xwm txheej tau pom tshwm sim thaum kev ntsuam xyuas rau lwm yam mob. Kev kho mob tsom mus rau kev hloov pauv txoj kev ua neej, xws li kev poob phaus, nrog rau kev tswj hwm ntawm cov teeb meem metabolic. Kev kho tshuaj kho mob tshiab tseem raug tshawb xyuas los hais txog cov txheej txheem tshwj xeeb uas tsav NASH kev vam meej.

Qhov zoo ntawm Non-Human Primate (NHP) Qauv rau NASH Kev Tshawb Fawb:

1.Closer Metabolic thiab Kab Mob Siab Homology:NHPs qhia qhov zoo sib xws nrog tib neeg nyob rau hauv cov ntsiab lus ntawm daim siab qauv thiab cov txheej txheem metabolic, suav nrog insulin rhiab heev, lipid metabolism, thiab inflammatory teb. Qhov no ua rau lawv tshwj xeeb tshaj yog tsim rau kev ua qauv ntawm pathophysiology ntawm NASH thiab rau kev sim tshuaj kho cov kev cuam tshuam uas lub hom phiaj metabolic thiab inflammatory pathways.

2.Txoj Kev Txhim Kho Cov Kab Mob Siab Zoo:NHPs, zoo li tib neeg, tuaj yeem txhim kho cov kab mob siab, suav nrog steatosis, o, fibrosis, thiab txawm tias cirrhosis, thaum noj cov zaub mov thiab cov xwm txheej uas ua rau tib neeg metabolic syndromes. Qhov kev nce qib no ua rau NHPs muaj txiaj ntsig rau kev kawm keeb kwm ntawm NASH thiab ntsuas qhov cuam tshuam ntev ntawm kev kho mob.

3.Immune System ntsig txog:Lub cev tiv thaiv kab mob ntawm NHPs zoo ib yam li tib neeg, tso cai rau kev kawm txog kev tiv thaiv kab mob hauv lub cev uas cuam tshuam nrog NASH kev loj hlob, xws li lub luag haujlwm ntawm macrophages, T hlwb, thiab inflammatory cytokines hauv daim siab raug mob thiab fibrosis. Qhov no yog qhov tseem ceeb rau kev tsim kho cov tshuaj tiv thaiv kab mob hauv NASH.

4.Tus nqi txhais lus rau kev kho mob:NHPs muab tus choj tseem ceeb hauv kev tshawb fawb kev txhais lus, tshwj xeeb tshaj yog rau kev ntsuas kev nyab xeeb thiab kev ua tau zoo ntawm kev kho tshuaj kho mob rau NASH. Lawv cov metabolic thiab kev tiv thaiv kab mob zoo sib xws rau tib neeg ua rau lawv zoo tagnrho rau kev tshawb fawb txog kev kho mob tshiab, suav nrog cov phiaj xwm fibrosis thiab mob, ua ntej hloov mus rau tib neeg kev sim tshuaj.

Qhov zoo ntawm NHP qauv piv rau Mouse Models rau NASH Kev Tshawb Fawb:

1.Closer Metabolic thiab Liver Pathophysiology Similarity:NHPs ua kom raug ntau dua cov teeb meem metabolic uas pom hauv tib neeg NASH, suav nrog insulin tsis kam, dyslipidemia, thiab daim siab mob. Cov nas, tshwj xeeb tshaj yog hom kab mob, tsis ua raws li cov txheej txheem metabolic no, txwv tsis pub lawv cov txiaj ntsig hauv kev kawm txog tib neeg NASH kev nce qib thiab cov lus teb kho mob.

2.Ntau yam kab mob sib kis:NHPs tuaj yeem txhim kho txhua theem ntawm NASH, los ntawm kev yooj yim steatosis mus rau qib siab fibrosis thiab cirrhosis, uas zoo dua qhia txog tib neeg kab mob. Hauv qhov sib piv, cov qauv nas feem ntau ua tsis tiav dhau qhov yooj yim steatosis lossis mob me me, txo lawv qhov cuam tshuam rau kev kawm tom qab theem ntawm NASH thiab kuaj cov tshuaj tiv thaiv fibrotic.

3.Kev Txhim Kho Cov Qauv Ua Haujlwm Zoo:NHPs muaj lub cev tiv thaiv kab mob uas zoo sib xws rau tib neeg, ua rau lawv cov qauv zoo tshaj plaws rau kev kawm txog lub luag haujlwm ntawm kev mob thiab kev tiv thaiv kab mob hauv NASH. Cov nas feem ntau pom cov kab mob sib txawv uas tsis tuaj yeem kwv yees qhov tshwm sim ntawm tib neeg, tshwj xeeb tshaj yog nyob rau hauv cov ntsiab lus ntawm lub siab mob thiab fibrosis.

4.Clinical Translation of Therapeutic Dosing and Mechanisms:Qhov loj dua thiab lub cev zoo sib xws ntawm NHPs rau tib neeg tso cai rau kev siv tshuaj ntau dua thiab xa cov neeg ua haujlwm kho mob, suav nrog cov tshuaj tshiab tsom rau txoj hauv kev metabolic thiab fibrotic hauv NASH. Cov kev tshawb pom los ntawm NHP qauv tau yooj yim dua txhais rau cov chaw kho mob piv rau cov qauv nas, tshwj xeeb tshaj yog rau kev ntsuas kev ua tau zoo thiab kev nyab xeeb ntawm kev kho mob rau tib neeg siv.