Kev Tshawb Fawb Ua Ntej Ntawm Cov Mob Ntshav Plasma Cytokines hauv Cov Me Nyuam Autism leej twg muaj Cov tsos mob ntawm plab zom mov Part 2
Jul 25, 2023
2.2. Kev Tshawb Fawb Txog Kev Tshawb Fawb
Cytokine thiab chemokine concentrations yog ntuj-log-hloov rau kev txheeb xyuas. Covariates ntawm kev txaus siab raws li qhov ua tau confounders suav nrog tus menyuam lub hnub nyoog ntawm cov ntshav kos. Kev tiv thaiv kab mob tuaj yeem hloov pauv raws hnub nyoog; yog li ntawd, nws yog ib qho tseem ceeb uas yuav tau kho lub hnub nyoog raws li ib tug confounder. Kev soj ntsuam ntawm kev sib txawv (ANCOVA), hloov kho rau lub hnub nyoog ntawm cov ntshav kos, tau ua los sib piv cov tshuaj ntsuam xyuas cov ntsiab lus hauv cov xwm txheej thiab tswj nrog thiab tsis muaj cov tsos mob GI.
Kho cov txhais tau tias thiab cov txheej txheem yuam kev tau nthuav tawm raws li cov txiaj ntsig tau piav qhia hauv pg / mL units. p-tus nqi raug kho rau ntau qhov kev sib piv siv txoj kev Tukey-Kramer thiab suav tias yog qhov tseem ceeb yog p < 0.05 tom qab siv cov kev kho. Txhua qhov kev ntsuam xyuas tau ua tiav siv SAS version 9.2 (SAS Institute Inc., Cary, NC, USA).
Cytokines yog cov protein tseem ceeb hauv lub cev uas tuaj yeem cuam tshuam kev loj hlob, kev sib txawv, thiab kev ua haujlwm ntawm txhua lub cell hauv lub cev. Kev tiv thaiv kab mob hauv lub cev kuj tseem cuam tshuam nrog cytokines.
Kev tiv thaiv kab mob yog lub cev tiv thaiv kab mob, kab mob, thiab lwm yam kab mob. Thaum lub cev raug cuam tshuam los ntawm cov kab mob los ntawm lub ntiaj teb sab nraud, lub cev tiv thaiv kab mob yuav tsim ntau lub hlwb thiab cov tshuaj tiv thaiv lub cev. Cov tshuaj no suav nrog ntau cytokines, uas tuaj yeem tswj hwm kev ua haujlwm ntawm cov qe ntshav dawb hauv lub cev tiv thaiv kab mob, txhawb kev tsim cov tshuaj tiv thaiv, thiab yog li txhim kho lub cev tiv thaiv kab mob.
Cytokines tuaj yeem ua ncaj qha rau cov kab mob, ua kom cov macrophages thiab NK hlwb los tua thiab tua cov kab mob. Tsis tas li ntawd, cytokines tseem tuaj yeem koom nrog hauv kev tswj hwm ntawm cov kab mob inflammatory thiab kev tiv thaiv kab mob, thiab ua lub luag haujlwm tseem ceeb hauv kev tshwm sim thiab kev loj hlob ntawm cov kab mob autoimmune.
Yog li, cytokines txaus ua lub luag haujlwm tseem ceeb hauv lub cev tiv thaiv kab mob. Cov kws tshawb fawb tseem tab tom kawm txog kev siv cytokines los txhim kho lub cev tiv thaiv kab mob. Qee cov tshuaj tiv thaiv kab mob thiab cov tshuaj tiv thaiv kab mob tau siv dav hauv kev tiv thaiv kab mob.
Hauv kev xaus, cytokines muaj feem xyuam nrog kev tiv thaiv kab mob, kev txhim kho ntawm kev tiv thaiv kab mob yuav tsum muaj kev tswj hwm ntawm cytokines, thiab cov cytokines txaus kuj tuaj yeem txhim kho kev tiv thaiv. Yog li ntawd, peb yuav tsum mob siab rau kev tswj hwm qhov sib npaug ntawm cytokines hauv peb lub cev kom tswj tau peb lub cev kev noj qab haus huv thiab kev tiv thaiv kab mob. Los ntawm qhov kev xav no, peb yuav tsum txhim kho peb txoj kev tiv thaiv. Cistanche tuaj yeem txhim kho kev tiv thaiv zoo vim tias cov polysaccharides hauv Cistanche tuaj yeem tswj kev tiv thaiv kab mob ntawm tib neeg lub cev tiv thaiv kab mob, txhim kho kev ntxhov siab ntawm lub cev tiv thaiv kab mob, thiab txhim kho cov kab mob bactericidal ntawm lub cev tiv thaiv kab mob.
Nyem qhov txiaj ntsig kev noj qab haus huv ntawm cistanche
3. Cov txiaj ntsig
Peb pom tsis muaj qhov sib txawv ntawm cov cytokines ntawm TD tswj uas muaj cov tsos mob GI thiab cov kev tswj TD uas tsis muaj cov tsos mob GI, tom qab kho tus me nyuam lub hnub nyoog ntawm cov ntshav (Table 1).
Ntawm cov neeg mob AU, piv rau cov tsis muaj GI cov tsos mob cov tsos mob GI muaj ntau dua innate immune cytokines, suav nrog; IFN {{0}} qib (hloov txhais tau tias 86.574 (tus qauv yuam kev 1.234) vs. 38.092 (1.241) pg/mL, p=0.04); IL-1 theem (23.999 (1.496) vs. 5.028 (1.513) pg/mL, p=0.04); TNF (21.672 (1.349) vs. 5.094 (1.358) pg/mL, p=0.006); thiab, IL-15 (3.561 (1.405) vs. 0.690 (1.418) pg/mL, p=0.006).
Rau cytokines feem ntau cuam tshuam nrog cov lus teb hloov kho lymphocyte, suav nrog; IL{{0}} (2.052 (1.391) vs. 0.525 (1.404) pg/mL, p=0.03); IL-12p70 (5.989 (1.332) vs. 1.954 (1.342) pg/mL, p=0.04); IL-4 (3.456 (1.432) vs. 0.669 (1.445) pg/mL, p=0.01); thiab, IL-13 (1.747 (1.568) vs. 15.502 [1.551] pg/mL, p=0.005), cov no tau nce siab hauv AU cov tsos mob nrog GI piv rau cov mob AU uas tsis muaj GI. cov tsos mob. Qhov zoo siab, kev tswj hwm cytokine IL-10 tau txo qis hauv AU cov neeg mob nrog cov tsos mob GI piv nrog cov tsis muaj cov tsos mob GI (1.504 (1.516) vs. 9.365 (1.499) pg/mL, p=0.01).
Lub ntsiab lus ntawm GM-CSF ntau dua hauv AU nrog GI cov tsos mob pab pawg piv nrog TD tswj tsis muaj cov tsos mob GI tom qab hloov kho rau tus menyuam hnub nyoog ntawm cov ntshav (16.248 (1.298) vs. 4.568 (1.298) pg/mL, p {{ 9}} 04; Table 1). Ntxiv mus, theem ntawm lwm yam innate cytokines tau nce rau IL-1 (23.999 (1.496) vs. 9.757 (1.383) pg/mL; p=0.011); IFN -2 (86.574 (1.234) vs. 50.3 (1.184) pg/mL; p=0.026); TNF (21.672 (1.1.349) vs. 8.248 (1.271) pg/mL; p=0.006) thiab IL-15 (3.561 (1.405) vs. 0.905(1.314) pg/mL; p=0.01) hauv AU nrog cov tsos mob GI piv nrog TD tswj tsis muaj cov tsos mob GI.
AU cov menyuam yaus uas muaj cov tsos mob GI tau muaj IL ntau dua {{0}}} ntau dua TD tswj nrog cov tsos mob GI (0.542 [1.707], p=0.03). Qib ntawm IL-13 kuj tseem ceeb dua hauv AU cov menyuam yaus uas muaj cov tsos mob GI piv rau qib hauv TD tswj nrog cov tsos mob GI (1.113 (1.923), p=0.03). IL-15 qib kuj tseem ceeb dua hauv AU cov menyuam yaus uas muaj cov tsos mob GI piv nrog cov menyuam yaus TD uas muaj cov tsos mob GI (0.499 (1.660), p=0.01).
Qhov ntau ntawm ob peb lwm cytokines sib txawv nyob rau hauv rooj plaub thiab tswj nrog thiab tsis muaj cov tsos mob GI tab sis tsis ncav cuag qhov tseem ceeb ntawm cov ntaub ntawv ntawm {{0}}.05. Qib IL-5 tau siab dua hauv AU cov menyuam uas muaj cov tsos mob GI piv nrog cov menyuam AU uas tsis muaj cov tsos mob GI (0.433 (1.504) vs. 0.106 ( 1.520) pg/mL, p=0.08); Ntxiv mus, IL-5 qib siab dua hauv AU cov menyuam uas muaj cov tsos mob GI piv rau cov menyuam yaus TD uas tsis muaj cov tsos mob GI (0.071 (1.839) pg/mL, p=0.07). AU cov menyuam yaus uas muaj cov tsos mob GI kuj muaj IL-6 ntau dua AU cov menyuam uas tsis muaj cov tsos mob GI (3.487 (1.492) vs. 0.886 (1.507) pg/mL, p=0.09), thiab AU cov menyuam yaus nrog Cov tsos mob GI muaj IL{31}} ntau dua li cov menyuam yaus TD uas tsis muaj cov tsos mob GI (0.583 (1.815) pg/mL, p=0.07). Ib yam li ntawd, IL-7 qib siab dua hauv AU cov menyuam yaus uas muaj cov tsos mob GI piv nrog cov menyuam yaus TD uas tsis muaj cov tsos mob GI (7.637 (1.381) vs. 1.848 (1.619), p=0.08).
4. Kev sib tham
Lub cev tiv thaiv kab mob ua lub luag haujlwm tseem ceeb hauv kev tiv thaiv tus tswv ntawm kev kis kab mob thiab tsis tu ncua los ntawm ob qho tib si sab nraud thiab sab hauv stimuli. Inflammation yog ib qho tseem ceeb tiv thaiv thiab ciaj sia teb, tshwm sim los ntawm innate thiab adaptive tiv thaiv mechanisms.
Txawm li cas los xij, kev mob tsis tu ncua lossis kev tiv thaiv kab mob tsis zoo tuaj yeem ua rau muaj kev cuam tshuam ntawm cov txheej txheem physiological hauv ob qho tib si tiv thaiv kab mob thiab tsis muaj zog. Tsis tas li ntawd, o ua rau muaj kev tsim cov pa oxygen ntau ntxiv uas tuaj yeem ua rau oxidative kev nyuaj siab thiab cov ntaub so ntswg puas.
Hauv AU, peb thiab lwm tus tau pom kev hloov pauv ntawm cov kab mob tiv thaiv kab mob, cov cim inflammatory, oxidative kev nyuaj siab, kev tiv thaiv kab mob hauv lub cev, thiab teb rau cov kab mob [3,5,10,34]. Hauv qhov kev tshawb fawb ua ntej no, peb pom tias cov menyuam yaus uas muaj AU thiab GI cov tsos mob tau nce qib ntawm innate cytokines IFN , IL-1a, IL-15, thiab TNF , thiab hloov cytokines IL-2, IL-4, IL-12 (p70), thiab IL-13, tab sis txo qis kev tswj hwm cytokine IL-10 piv nrog cov menyuam yaus uas muaj AU tsis muaj cov tsos mob GI.
Hauv TD tswj peb pom tsis muaj qhov sib txawv raws li cov tsos mob GI. AU cov menyuam yaus uas muaj cov tsos mob GI muaj ntau dua IL-4 thiab IL-13 ntau dua li TD tswj nrog cov tsos mob GI. Ntxiv mus, ntau yam cytokines innate tau nce hauv cov menyuam yaus nrog AU nrog cov tsos mob GI piv nrog TD tswj tsis muaj cov tsos mob GI suav nrog, GM-CSF, IL-1, IFN -2, thiab TNF .
Thaum kawg, cov mucosal-hais txog cytokine IL-15 kuj tau nce hauv AU nrog cov tsos mob GI piv rau ob qho tib si TD tswj thiab cov uas tsis muaj cov tsos mob GI. Cov ntaub ntawv no qhia tias tej zaum yuav muaj cov qauv sib txawv ntawm cov plasma cytokines hauv cov menyuam yaus uas muaj AU nyob ntawm seb muaj cov kab mob sib kis xws li cov tsos mob GI.
Lub hauv paus / kev siv hluav taws xob ntawm cov cim lom lossis kos npe hauv AU yog qhov yooj yim; los pab rau kev kuaj mob, pab saib xyuas kev kho mob / kev cuam tshuam, thiab taw tes rau cov kab mob pathological koom nrog hauv kev ua rau muaj kev cuam tshuam. Txawm li cas los xij, kev siv cov cim kev lom neeg rau hauv kev tshawb fawb lossis chaw kho mob hauv AU yog qhov tsis yooj yim thiab tam sim no tau kawm ntau heev.
Piv txwv li, hauv txoj kev tshawb no qhov sib txawv ntawm cov plasma biomarkers tsuas yog pom tseeb hauv AU pab pawg nrog cov tsos mob GI thiab tsis yog cov tsis muaj cov tsos mob GI, tom qab kho lub hnub nyoog ntawm cov menyuam yaus cov ntshav thiab kho cov lej rau ntau qhov sib piv. Qhov no tuaj yeem cuam tshuam qhov sib txawv ntawm kev tiv thaiv kab mob hauv AU pawg nrog GI lossis tias pawg AU tsis muaj GI yog ntau dua heterogeneous.
Raws li cov cuab yeej muaj nyob rau hauv txoj kev tshawb fawb CHARGE (piv txwv li, kev soj ntsuam siv VABS, MSEL, ADOS, thiab ADI-R;), peb tsis tuaj yeem nthuav tawm cov kev mob tshwm sim ntxiv hauv AU xws li kev ntxhov siab, kev tsis txaus siab ntawm kev xav tsis zoo, lossis lub hlwb loj. kev loj hlob uas kuj yuav muaj lub hauv paus tiv thaiv kab mob hauv cov neeg koom hauv txoj kev tshawb fawb. Cov kab mob sib kis no tuaj yeem tshwm sim hauv AU pab pawg, txawm li cas los xij, raws li kev ntsuas tam sim no tsis muaj qhov sib txawv ntawm cov qhab nia ntawm ob pawg AU.
Cov kev tshawb fawb ntxiv nrog cov qauv loj dua tau lees paub los tshawb xyuas seb lwm cov kab mob sib kis puas tuaj yeem raug txheeb xyuas siv cov plasma cytokines. Raws li qhov sib txawv hauv pawg AU, kuj tseem muaj qhov sib txawv ntawm AU nrog GI thiab TD tswj, nrog thiab tsis muaj teeb meem GI hauv cov ntshav cytokine qib; Qhov no ntxiv qhov muaj peev xwm ntxiv rau plasma cytokines raws li kev kos npe lom neeg rau GI co-morbidities.
Kev tsim tawm ntau ntxiv ntawm IL-15 hauv AU nrog GI piv nrog AU tsis muaj GI thiab ob qho tib si TD (nrog thiab tsis muaj cov tsos mob GI) muaj ntau qhov cuam tshuam rau mucosal tiv thaiv kab mob. IL-15 yog tsim los ntawm cov hlwb epithelial hauv lub plab thiab lub cev tiv thaiv kab mob xws li macrophages, thiab dendritic cells. IL-15 txhawb nqa T cell proliferation thiab cytokine ntau lawm, cuam tshuam qhov kev qhia ntawm mucosal adhesion integrin- E 7- ntawm intraepithelial T hlwb, thiab nws kuj tuaj yeem ua rau kev loj hlob ntawm plab hnyuv epithelial hlwb [35].
Hauv cov kab mob GI, IL -15 yog overexpressed nyob rau hauv lub plab mucosa ntawm cov neeg mob uas muaj kab mob celiac thiab xav tias yuav pab txhawb rau epithelial puas [36]. Kev noj qab haus huv ntawm GI ib puag ncig yog nyob ntawm qhov ua tsis zoo ntawm lub plab ua haujlwm hauv ib feem tswj hwm los ntawm kev sib tshuam nruj nyob rau hauv nruab nrab ntawm cov enterocytes. Siv cov lactulose: mannitol test, txo cov plab hnyuv permeability tau pom nyob rau hauv autism [37,38].
Ntxiv mus, ib qho kev tshawb fawb yav dhau los qhia tau hais tias 75 feem pua ntawm cov kab mob hauv plab uas cais tawm los ntawm cov neeg uas muaj kev puas siab puas ntsws tau txo qis kev qhia txog kev thaiv kev sib tshuam, thiab 66 feem pua tau nce pore-forming claudins thaum piv rau kev tswj [39]. Peb kuj tau qhia txog kev hloov pauv hauv cov noob tswj cov qib zonulin, cov molecule uas tswj cov hnyuv permeability, hauv cov menyuam yaus uas muaj cov tsos mob GI tab sis tsis yog AU yam tsis muaj GI cov tsos mob lossis kev tswj hwm [10].
IL-15 kuj tseem koom nrog hauv kev ua kom NK hlwb ib qho kev tshawb pom yav dhau los pom hauv autism [5]. Tsis tas li ntawd, IL-15 tuaj yeem thaiv kev tswj hwm T-cell tiam los ntawm kev ua IL-12p70 ntau lawm hauv dendritic hlwb [40]. Txo kev tswj hwm T-cell tsim tau pom nyob rau hauv autism [22,41]. Hauv txoj kev tshawb fawb tam sim no, peb kuj pom tau nce IL -12p70 hauv AU nrog cov tsos mob GI.
Qhov sib txawv ntawm lwm cov cytokines innate kuj tau sau tseg hauv AU nrog cov tsos mob GI. Lub cev tiv thaiv kab mob hauv lub cev ua haujlwm ua thawj kab ntawm kev tiv thaiv thiab tau tshwm sim los ntawm cov qauv lees paub receptors xws li Tus Xov Tooj Zoo li receptors (TLR). Hauv cov kab mob GI, cov kev sib cuam tshuam no tseem ceeb vim tias muaj peev xwm los teb rau cov kab mob commensal, cov kab mob hauv cov zaub mov, lossis cov kab mob los ntawm cov khoom.
Cov hlwb loj ntawm lub cev tsis muaj zog muaj xws li macrophages, dendritic cells, NK hlwb, thiab neutrophils. Perivascular macrophages thiab microglia (ib hom tshwj xeeb ntawm macrophage) yog cov neeg nyob hauv lub cev tiv thaiv kab mob hauv lub hlwb thiab tiv thaiv kev puas tsuaj lossis kab mob. Kev hloov pauv hauv cov lus teb hauv lub cev thiab microglia muaj nuj nqi txuas rau ntau yam kab mob neurodevelopmental, suav nrog autism [5].
Lub paj hlwb mob nrog lub tshuab ua kom muaj microglia thiab astrocytes uas cuam tshuam rau kev sib txuas ntawm neuronal nrog kev poob ntawm kev sib txuas ntawm synaptic thiab neuronal cell tuag tau piav qhia hauv ASD [42]. Cov kev tshawb fawb tseem qhia txog qib siab ntawm cov cytokines pro-inflammatory xws li IL-1 , IFN, TNF, thiab IL-8 ob qho tib si hauv lub cev thiab hauv hlwb [5]. Lub caij no, cov tshuaj tiv thaiv cytokines, xws li hloov pauv kev loj hlob beta1 (TGF 1), thiab IL-35 tau txo qis hauv AU [10,25,27,42].
Interestingly, ntau qhov kev tshawb fawb qhia txog kev sib koom ua ke ntawm qhov hnyav ntawm AU-txog kev coj cwj pwm thiab qib cytokine, [3,13,43]. Ntawm qhov kev ceeb toom, innate cytokine IL-1 tuaj yeem cuam tshuam rau hypothalamic-pituitary-adrenal (HPA) axis, thiab IL-6 muaj lub luag haujlwm tseem ceeb hauv kev txhim kho neuro ntxov ntxov thiab kev sib txuas lus neuro-immune [5].
Ntxiv rau qhov kev hloov pauv ntawm qhov sib npaug ntawm innate cytokines thiab IL-12, peb kuj pom qhov nce hauv cytokines cuam tshuam nrog atopy hauv AU nrog cov tsos mob GI. IL-4 thiab IL-13 yog txuam nrog cov lus teb humoral thiab yog tus tsav tsheb ntawm o hauv atopy thiab zaub mov tsis haum [40,46]. Autism yav dhau los tau cuam tshuam nrog kev ua xua zaub mov ntau ntxiv thiab mob hawb pob [44–48]. Nce IL-4 kuj tau pom nyob rau hauv cov ntshav me nyuam mos los ntawm cov menyuam yaus uas tom qab tsim mob hnyav AU [49]. Cov kev tshawb fawb ntxiv los tshawb xyuas biomarkers thiab zaub mov ua xua hauv AU tau lees paub.
Tsis tas li ntawd, lwm qhov sib txawv ntawm pawg AU yog qhov txo cov ntshav plasma ntawm IL-10 uas tuaj yeem qhia qhov tsis txaus ntseeg hauv kev tiv thaiv kab mob. Peb, thiab lwm tus, tau pom qhov txo qis hauv cov ntshav ntshav ntawm lwm cov kev tswj hwm cytokines xws li TGF 1 thiab IL-35 qib hauv cov neeg laus thiab menyuam yaus nrog AU [25,27,50]. Ntau cov ntawv tshaj tawm kuj tau pom tias txo qis IL-10 qib hauv T hlwb hauv cov menyuam yaus uas muaj kev puas hlwb [17,18,22,51]. Kev tswj hwm lub cev tiv thaiv kab mob homeostasis yog qhov sib npaug ntawm kev muab kev tswj hwm / kev ua siab ntev rau tus kheej cov protein thiab tseem ceeb cov txiaj ntsig zoo microbes, thiab teb rau cov kab mob microbes. Cov kev tshawb fawb yav dhau los tshawb xyuas cov lus teb txhawb zog hauv lub cev tiv thaiv kab mob hauv AU cov menyuam yaus pom tias cov neeg uas tau cim qhov kev hloov pauv ntawm tus cwj pwm thiab cov tsos mob GI, tau txo qis IL-10 rau qee yam kev tiv thaiv kab mob [23,24].
Thaum cov kws kho mob muaj zog tuaj yeem pab txhim kho kev tiv thaiv zoo rau cov kab mob, kev cuam tshuam hauv kev tswj hwm tuaj yeem ua rau mob hnyav heev thiab tau cuam tshuam rau ntau yam kab mob autoimmune nrog rau cov uas cuam tshuam rau GI xws li Crohn's kab mob thiab mob plab ulcerative [52-55].
Cov kev tshawb fawb tsis ntev los no qhia tau hais tias cov tshuaj tiv thaiv kab mob tuaj yeem cuam tshuam rau lub plab microbiome, nrog rau lub paj hlwb, thiab tej zaum yuav koom nrog hauv pathology ntawm AU [4]. Piv txwv li, lub cev tiv thaiv kab mob tuaj yeem tsim cov microbiome muaj pes tsawg leeg los ntawm kev tsim cov tshuaj tiv thaiv kab mob xws li -defensins thiab -defensins, qhov kev hloov pauv tuaj yeem ua rau IgA, thiab T hlwb uas tshwj xeeb rau cov kab mob commensal [56-58]. Tsis tas li ntawd, kev tsim cov pa oxygen reactive vim cov lus teb inflammatory tuaj yeem ua rau muaj kev loj hlob ntawm cov kab mob tshwj xeeb, hloov cov microbiome muaj pes tsawg leeg.
Hloov microbiota muaj pes tsawg leeg feem ntau pom hauv AU; Txawm li cas los xij, qhov ua rau ntawm qhov no tsis paub thiab tej zaum yuav cuam tshuam rau cov zaub mov rhiab heev lossis kev nyiam noj zaub mov [59]. Ntxiv mus, nws tsis ntev los no tau pom tias GI cov tsos mob hauv AU tsis cuam tshuam nrog kev hloov pauv microbiome hauv AU [60], thaum peb qhia ntawm no thiab yav dhau los, tias kev tiv thaiv kab mob thiab ntshav cytokines cuam tshuam nrog GI cov tsos mob hauv AU [10,22,25] . Cov kev tshawb fawb ntxiv yog xav tau los qhia meej txog lub luag haujlwm ntawm lub cev tiv thaiv kab mob hauv lub plab - lub hlwb, nrog rau kev sib cuam tshuam ntawm lub cev tiv thaiv kab mob, plab hnyuv ua haujlwm, microbiome, thiab lub paj hlwb thiab lub paj hlwb peripheral.
Raws li kev tshawb fawb ua ntej, muaj ntau yam kev txwv. Peb txoj kev tshawb fawb yog txwv los ntawm cov qauv me me uas cuam tshuam txog kev txheeb xyuas tus cwj pwm hauv cov pab pawg thiab txwv tsis pub peb yuav ua li cas rau peb cov neeg kawm.
Peb tsis tau pom cov pov thawj rau kev kwv yees cov cim ntawm lub xeev thiab cov yam ntxwv zoo nrog ib qho cytokine siv thaj chaw hauv qab qhov nkhaus (AUC) kev tshuaj xyuas (cov ntaub ntawv tsis qhia) qhov tseeb uas feem ntau yuav cuam tshuam txog ntau qhov sib txawv uas xav tau kho thiab pab pawg me me. . Raws li nrog rau lwm cov kev tshawb fawb, kev nrhiav neeg ua haujlwm ntawm TD cov menyuam yaus uas ntsib teeb meem GI yog qhov nyuaj vim lawv qhov tsawg zaus hauv cov pej xeem hauv pawg hnub nyoog no. Peb tsom mus rau cov tsos mob ntawm lub plab zom mov tsis xwm yeem raws li cov yav tas los no tau muaj feem cuam tshuam nrog cov tsos mob GI hauv AU [1,3].
Vim muaj tus lej tsawg, peb tsis tuaj yeem sib cais pawg ntxiv los tshuaj xyuas qhov sib txawv ntawm cov kab mob GI tshwj xeeb (piv txwv li, cem quav vs. diarrhea vs. IBS) tab sis qhov no ua rau kev kawm ntxiv. Raws li kev nrhiav neeg ua haujlwm ntawm cov txiv neej thiab poj niam tau ua raws li AU kev kuaj mob, peb tsis muaj peev xwm txheeb xyuas qhov sib txawv ntawm kev sib deev vim muaj cov poj niam tsawg tsawg hauv ib pab pawg.
Thaum kawg, peb txoj kev tshawb fawb suav nrog cov hnub nyoog nqaim (cov tub ntxhais hluas), hauv kev tshawb nrhiav tom qab nws yuav raug lees paub los sib piv cov ntshav cytokines hauv cov hnub nyoog laus kom pom tias GI cov tsos mob hloov pauv li cas thiab lawv cuam tshuam li cas nrog cov ntshav cytokines thoob plaws hnub nyoog. Tsis tas li ntawd, hauv txoj kev tshawb no peb tsis tuaj yeem txiav txim siab qhov kev taw qhia ntawm qib cytokine siab, piv txwv li, nws puas tsim nyob rau hauv lub plab epithelium, lamina propria, mesenteric lymph nodes, lossis daim siab? Txawm li cas los xij, txawm tias muaj cov kev txwv no, peb xav tias txoj kev tshawb no muab cov ntsiab lus tseem ceeb rau cov ntshav cytokines thiab cov tsos mob GI hauv cov menyuam yaus nrog AU.
Vim yog qhov heterogeneity ntawm AU thiab ntau hom kev tiv thaiv kab mob tsis ua haujlwm tau tshaj tawm, peb tau nrhiav kev tshawb nrhiav qhov sib txawv ntawm cov plasma cytokines nyob rau hauv ib pawg ntawm cov menyuam yaus raws li comorbidity ntawm GI cov tsos mob. Lub hom phiaj tseem ceeb ntawm txoj kev tshawb no yog txhawm rau txheeb xyuas qhov sib txawv ntawm cov kab mob plasma cytokines hauv AU nrog thiab tsis muaj cov tsos mob GI piv nrog cov menyuam yaus TD. Cov menyuam yaus uas muaj AU thiab GI cov tsos mob tau pom qhov sib txawv loj tshaj plaws nrog cov kab mob cytokines siab thiab txo cov kev tswj hwm IL-10 piv nrog AU uas tsis muaj cov tsos mob GI. Mucosal-relevant IL-15 tau nce hauv AU nrog cov tsos mob GI piv nrog txhua pab pawg. Peb yav dhau los tau tshaj tawm txog kev hloov pauv lub cev tiv thaiv kab mob hauv cov menyuam yaus nrog AU uas muaj cov tsos mob GI. Peripheral ntshav mononuclear hlwb los ntawm cov menyuam yaus uas muaj AU thiab GI cov tsos mob ua rau cov mucosa ntsig txog cytokines tab sis txo qis TGF 1 tom qab stimulation hauv vitro [10], qhia txog qhov tsis sib npaug ntawm cov lus teb.
Cov ntaub ntawv no, nrog rau txoj kev tshawb fawb tam sim no, qhia txog qhov yuav tsum tau nrhiav cov pab pawg sib koom hauv AU, uas tuaj yeem pab txhais cov kev kho mob ntau dua kom muaj txiaj ntsig rau tib neeg thoob plaws spectrum [1]. Lub teb ntawm AU xav tau kev tshawb nrhiav ntxiv los piav qhia txog cov kab mob sib txawv ntawm qhov dav dav ntawm cov xwm txheej thiab cov kab mob sib kis. Qhov no ua rau cov lus nug ntawm yuav ua li cas peb tuaj yeem kho cov kab mob plab hnyuv hauv cov ntsiab lus ntawm AU. Piv txwv li, kev tiv thaiv kab mob puas tuaj yeem pab kho cov hnyuv homeostasis, thiab cov tshuaj tiv thaiv kab mob twg yuav tsum tau tsom? Peb cov ntaub ntawv qhia ob qhov chaw ua tau, xws li txo qis cytokines inflammatory los yog nce kev tiv thaiv kab mob. Cov kev tshawb fawb yav tom ntej tuaj yeem tsom mus rau kev tiv thaiv kab mob hauv lub plab hauv AU los pab tshem tawm txoj hauv kev, thiab kev tiv thaiv kab mob hauv cov menyuam yaus nrog AU nrog GI co-morbidities.
Nyiaj txiag:
Txoj kev kawm no tau txais nyiaj los ntawm Autism Speaks Foundation (Grant #7567), Lub Tsev Haujlwm Saib Xyuas Kev Noj Qab Haus Huv Hauv Tebchaws, muab R21HD086669, P01 ES011269-11, R01MH118209, R01HD090214, R01ES015359, NARSAD Foundations Jane, Michael thiab Barbara Basford Foundation , Jonty Foundation, thiab Brain Foundation. Txoj haujlwm no tau txais kev txhawb nqa los ntawm Lub Tsev Haujlwm Saib Xyuas Kev Tiv Thaiv, dhau los ntawm Kev Tshawb Fawb Kev Tshawb Fawb Autism raws li Award No. W81XWH-18-1-0681. Cov kev xav, kev txhais lus, cov lus xaus, thiab cov lus pom zoo yog cov neeg sau ntawv thiab tsis tas yuav pom zoo los ntawm Lub Tsev Haujlwm Saib Xyuas Kev Tiv Thaiv lossis NIH.
Institutional Review Board Statement:
CHARGE Study raws tu qauv tau pom zoo los ntawm lub koom haum tshuaj xyuas pawg thawj coj ntawm University of California hauv Davis thiab Lub Xeev California Pawg Neeg Saib Xyuas Kev Tiv Thaiv Tib Neeg (IRB ID: 226028-33).
Cov Lus Qhia Txog Kev Pom Zoo:
Sau ntawv tso cai tau txais ua ntej kev koom tes.
Cov ntaub ntawv muaj nyob:
Cov ntaub ntawv muaj nyob rau ntawm kev thov.
Kev lees paub:
Peb xav ua tsaug rau cov neeg tuaj koom thiab lawv tsev neeg rau lawv txoj kev koom tes hauv txoj kev kawm thiab cov neeg ua haujlwm ntawm University of California Davis MIND Institute thiab CHARGE project rau lawv cov kev txhawb nqa. Peb xav ua tsaug rau Paula Krakowiak rau nws cov lus qhia thiab kev txhawb nqa.
Kev tsis sib haum xeeb ntawm kev txaus siab:
Cov kws sau ntawv tshaj tawm tsis muaj kev sib cav txog kev txaus siab.
Cov ntaub ntawv
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