xov xwm

Cachexia yog ib qho kab mob uas tshwm sim los ntawm kev poob phaus, cov leeg nqaij thiab cov nqaij adipose atrophy, thiab cov kab mob hauv lub cev. Cachexia yog ib qho teeb meem loj thiab ua rau tuag rau cov neeg mob qog noj ntshav. Ntxiv nrog rau kev mob qog noj ntshav, cachexia tuaj yeem tshwm sim los ntawm ntau yam mob ntev, tsis muaj kab mob, nrog rau lub plawv tsis ua haujlwm, lub raum tsis ua haujlwm, kab mob obstructive pulmonary, kab mob neurological, AIDS, thiab mob caj dab rheumatoid. Nws kwv yees tias qhov tshwm sim ntawm cachexia hauv cov neeg mob qog noj ntshav tuaj yeem ncav cuag 25% txog 70%, uas cuam tshuam rau cov neeg mob lub neej zoo (QOL) thiab ua rau muaj kev cuam tshuam txog kev kho mob.

Kev cuam tshuam zoo ntawm cachexia yog qhov tseem ceeb rau kev txhim kho lub neej zoo thiab kev cia siab ntawm cov neeg mob qog noj ntshav. Txawm li cas los xij, txawm tias qee qhov kev nce qib hauv kev kawm txog cov txheej txheem pathophysiological ntawm cachexia, ntau cov tshuaj tsim los ntawm cov txheej txheem ua tau tsuas yog qee qhov ua tau zoo lossis tsis muaj txiaj ntsig. Tam sim no tsis muaj kev kho mob uas tau pom zoo los ntawm US Food and Drug Administration (FDA).

Muaj ntau qhov laj thawj rau qhov tsis ua tiav ntawm kev sim tshuaj ntawm cachexia, thiab qhov laj thawj tseem ceeb yuav nyob hauv qhov tsis muaj kev nkag siab zoo ntawm cov txheej txheem thiab cov txheej txheem ntuj tsim ntawm cachexia. Tsis ntev los no, xibfwb Xiao Ruiping thiab tus kws tshawb fawb Hu Xinli los ntawm College of Future Technology ntawm Peking University tau koom ua ke luam tawm ib tsab xov xwm hauv Nature Metabolism, qhia txog lub luag haujlwm tseem ceeb ntawm lactic-GPR81 txoj hauv kev tshwm sim ntawm kev mob qog noj ntshav cachexia, muab lub tswv yim tshiab rau kev kho mob cachexia. Peb xaus qhov no los ntawm kev sib txuas cov ntaub ntawv los ntawm Nat Metab, Science, Nat Rev Clin Oncol thiab lwm cov ntawv sau.

Kev poob phaus feem ntau yog tshwm sim los ntawm kev noj zaub mov kom tsawg thiab / lossis siv zog ntxiv. Cov kev tshawb fawb yav dhau los tau qhia tias cov kev hloov pauv ntawm lub cev hauv cov qog nqaij hlav cachexia yog tsav los ntawm qee yam cytokines secreted los ntawm cov qog microenvironment. Piv txwv li, yam xws li kev loj hlob sib txawv ntawm 15 (GDF15), lipocalin-2 thiab insulin-zoo li protein 3 (INSL3) tuaj yeem cuam tshuam kev noj zaub mov los ntawm kev khi rau kev noj qab haus huv cov chaw tswj hwm hauv nruab nrab lub paj hlwb, ua rau cov neeg mob anorexia. IL-6, PTHrP, activin A thiab lwm yam ua rau poob phaus thiab cov nqaij mos atrophy los ntawm kev ua kom txoj hauv kev catabolic thiab nce kev siv zog. Tam sim no, kev tshawb fawb ntawm cov txheej txheem ntawm cachexia tau tsom mus rau cov proteins zais cia, thiab qee qhov kev tshawb fawb tau koom nrog kev koom tes ntawm cov qog metabolites thiab cachexia. Xib fwb Xiao Ruiping thiab tus kws tshawb fawb Hu Xinli tau coj txoj hauv kev tshiab los qhia txog cov txheej txheem tseem ceeb ntawm cov qog nqaij hlav cachexia los ntawm kev xav ntawm cov qog metabolites.

Ua ntej, Xib Fwb Xiao Ruiping pab pawg tau tshuaj xyuas ntau txhiab tus metabolites hauv cov ntshav ntawm kev tswj hwm kev noj qab haus huv thiab cov nas qauv ntawm lub ntsws cancer cachexia, thiab pom tias lactic acid yog cov metabolite loj tshaj plaws hauv cov nas nrog cachexia. Cov qib lactic acid hauv cov ntshav nce ntxiv nrog cov qog loj hlob, thiab pom tias muaj kev sib raug zoo nrog qhov hnyav ntawm cov qog nqaij hlav nas. Cov qauv kuaj ntshav tau sau los ntawm cov neeg mob qog noj ntshav tau lees paub tias lactic acid kuj tseem ua lub luag haujlwm tseem ceeb hauv kev loj hlob ntawm tib neeg mob qog noj ntshav cachexia.

Txhawm rau txiav txim siab seb qib siab ntawm lactic acid ua rau cachexia, pab pawg tshawb fawb tau xa cov lactic acid rau cov ntshav ntawm cov nas noj qab haus huv los ntawm lub twj tso kua mis osmotic cog rau hauv qab ntawm daim tawv nqaij, ua kom cov ntshav lactic acid nce qib rau cov nas nrog cachexia. Tom qab 2 lub lis piam, cov nas tsim ib qho phenotype ntawm cachexia, xws li poob phaus, rog thiab nqaij nqaij atrophy. Cov txiaj ntsig no qhia tias lactate-induced fat remodeling zoo ib yam li induced los ntawm cov qog nqaij hlav cancer. Lactate tsis yog tsuas yog tus yam ntxwv metabolite ntawm mob qog noj ntshav cachexia, tab sis kuj yog tus neeg nruab nrab tseem ceeb ntawm kev mob qog noj ntshav vim hypercatabolic phenotype.

Tom ntej no, lawv pom tias kev tshem tawm ntawm lactate receptor GPR81 tau ua haujlwm zoo hauv kev txo cov qog thiab cov ntshav lactate-induced cachexia tshwm sim yam tsis muaj kev cuam tshuam rau cov ntshav lactate. Vim tias GPR81 tau qhia ntau heev hauv cov ntaub so ntswg adipose thiab kev hloov hauv cov ntaub so ntswg adipose ua ntej tshaj cov leeg pob txha thaum lub sij hawm kev loj hlob ntawm cachexia, qhov tshwj xeeb knockout nyhuv ntawm GPR81 nyob rau hauv nas adipose ntaub so ntswg zoo ib yam li lub cev knockout, txhim kho qog-induced yuag poob thiab rog thiab skeletal nqaij noj. Qhov no qhia tias GPR81 nyob rau hauv cov ntaub so ntswg adipose yuav tsum tau rau kev loj hlob ntawm mob qog noj ntshav cachexia tsav los ntawm lactic acid.

Cov kev tshawb fawb ntxiv tau lees paub tias tom qab khi rau GPR81, lactic acid molecules tsav fatty Browning, lipolysis thiab ua kom lub cev kub ntau dhau los ntawm Gβγ-RhoA / ROCK1-p38 txoj kev taw qhia, tsis yog txoj hauv kev PKA classical.

Txawm hais tias muaj txiaj ntsig zoo hauv cov kab mob qog noj ntshav uas cuam tshuam txog cachexia, cov kev tshawb pom no tseem tsis tau txhais mus rau hauv kev kho mob zoo, yog li tam sim no tsis muaj cov qauv kev kho mob rau cov neeg mob no, tab sis qee lub zej zog, xws li ESMO thiab European Society of Clinical Nutrition and Metabolism, tau tsim cov txheej txheem kho mob. Tam sim no, cov txheej txheem thoob ntiaj teb pom zoo kom txhawb cov metabolism hauv thiab txo cov catabolism los ntawm txoj hauv kev xws li khoom noj khoom haus, kev tawm dag zog thiab tshuaj noj.