Qhov Tseem Ceeb Minerals Thiab Metabolic Adaptation Of Immune Cells Part 1

Abstract:

Cov kev ua neej niaj hnub no tau hloov pauv ntau dhau los ntawm cov poj koob yawm txwv niaj hnub mus rau kev hloov pauv loj hauv kev noj haus thiab nce sedentarism. Cov kab mob ntawm tib neeg lub cev tsis tau txais kev txhawb nqa los ntawm micronutrient-inferior farmed nqaij thiab qoob loo cov khoom lag luam uas tsim los ntawm cov khoom noj ua liaj ua teb uas twb muaj lawm. Qhov no yog qhov tshwj xeeb tshaj yog pom nyob rau hauv kev nce obesogenic adipogenesis thiab qis-qib o uas tsis daws nrog lub sijhawm. Cov metabolically txwv ib puag ncig ntawm cov ntaub so ntswg ua rau ua kom muaj zog thiab kev loj hlob ntawm cov neeg nyob ib puag ncig thiab cov neeg nyob hauv lub cev tiv thaiv kab mob hauv kev pom zoo ntawm cov tshuaj tiv thaiv kab mob, nrog rau ib feem ntawm kev txhim kho autoimmune teb.

Kev sib raug zoo ntawm kev rog thiab kev tiv thaiv kab mob yog qhov nyuaj heev. Feem ntau cov kev tshawb fawb tau pom tias kev rog rog tuaj yeem ua rau muaj qhov txawv txav ntawm lub cev tiv thaiv kab mob, uas ua rau muaj kev pheej hmoo ntawm qee yam kab mob, xws li ntshav qab zib, kab mob plawv, thiab qee yam mob qog noj ntshav. Antibody qib rau qee yam kab mob. Cov hauv qab no yog kev sib raug zoo ntawm kev rog thiab kev tiv thaiv kab mob:

1. Kev rog dhau tuaj yeem ua rau mob ntev, uas ua rau muaj kev cuam tshuam rau kev tswj hwm kev tiv thaiv kab mob thiab txo kev tiv thaiv. Qhov no yog vim cov rog rog secretes series ntawm cytokines thiab inflammatory yam, xws li interleukin -6 (IL-6), qog necrosis factor- (TNF- ), C-reactive protein (CRP), thiab lwm yam. , uas Factors ua rau inflammatory teb, thiab mob o tuaj yeem ua rau lub cev tsis muaj zog.

2. Cov rog rog yuav tso qee cov tshuaj lipid tsis zoo, xws li cov rog dawb thiab cov tshuaj lipid inflammatory. Lub hav zoov ntawm cov tshuaj no yuav cuam tshuam rau lub cev tiv thaiv kab mob thiab txo nws txoj kev tiv thaiv.

3. Kev rog rog yuav ua rau muaj cov kab mob pro-inflammatory ntau ntxiv, xws li macrophages, cov kab mob tua kab mob ntuj, thiab cov rog rog uas muaj feem xyuam nrog T hlwb, uas tuaj yeem tso tawm ntau cov cytokines thiab cov kab mob inflammatory, ntxiv dag zog rau lub xeev inflammatory. lub cev.

4. Kev loj hlob ntawm adipocytes ntau dhau ua rau lub cev tiv thaiv kab mob nkag mus rau hauv lub cev, uas ua rau muaj kev mob ntev thiab kev tiv thaiv kab mob.

Hauv kev xaus, kev rog thiab rog tuaj yeem cuam tshuam tsis zoo rau lub cev tiv thaiv kab mob, uas ua rau muaj kev pheej hmoo ntawm qee yam kab mob. Yog li ntawd, kev poob phaus, txhim kho koj tus cwj pwm noj mov, thiab tswj kev noj qab haus huv tuaj yeem pab txhawb koj lub cev tiv thaiv kab mob. Los ntawm qhov kev xav no, peb yuav tsum tau saib xyuas tshwj xeeb rau kev txhim kho peb txoj kev tiv thaiv kab mob. Cistanche tuaj yeem txhim kho kev tiv thaiv zoo. Nqaij tshauv muaj ntau yam tshuaj lom neeg lom neeg, xws li polysaccharides, ob lub nceb, Huang Li, thiab lwm yam. Ua kom muaj ntau lub hlwb ntawm lub cev tiv thaiv kab mob thiab ua kom lawv lub cev tiv thaiv kab mob.

Nyem cistanche deserticola ntxiv

Raws li cov theem sib txawv ntawm kev tiv thaiv kab mob thiab kev daws teeb meem nyob ntawm seb muaj cov zaub mov tshwj xeeb los tswj cov txheej txheem kev ncaj ncees ntawm daim tawv nqaij thiab cov hnoos qeev, kev ua kom thiab txav chaw ntawm lub cev tiv thaiv kab mob, ua kom lub zog ntxiv, thiab tso tawm cov pro-inflammatory cytokines thiab chemokines. , qhov kev tshuaj xyuas no tham txog kev nce qib tsis ntev los no hauv peb txoj kev nkag siab txog kev koom tes ntawm cov pob zeb hauv av hauv kev ua kom zoo rau cov lus teb ntawm innate thiab adaptive tiv thaiv kab mob. Kev pom luv luv ntawm kev nqus, thauj, thiab xa cov zaub mov mus rau lub cev cov ntaub so ntswg raws li kev cuam tshuam rau metabolic adaptation yog xam.

Ntsiab lus:

micronutrients; kev noj zaub mov tsis txaus; macrophage polarization; txoj hnyuv tiv thaiv kab mob; mucosal kev ncaj ncees; kev noj zaub mov.

1. Taw qhia

Txoj kev ua neej tshiab tau hloov zuj zus hauv 80 xyoo dhau los, vim feem ntau ntawm kev hloov pauv ntawm kev noj haus thiab kev nce hauv sedentarism. Cov xwm txheej no tau ua rau muaj kev nce ntxiv ntawm cov kab mob tsis sib kis, suav nrog cov kab mob ntev uas cuam tshuam nrog plaub qhov kev hloov pauv hauv lub cev thiab lub cev (nce ntshav qabzib, nce LDL cholesterol, lub cev hnyav lossis rog, thiab ntshav siab). Lub Chaw Tiv Thaiv Kab Mob thiab Kev Tiv Thaiv daim duab qhia tau zoo taug qab qhov kev rog rog hauv Teb Chaws Asmeskas lub sijhawm no, nrog kwv yees qhov nruab nrab nce ntawm 15 kg ntawm lub cev hnyav, 4.5 BMI units, thiab 18 cm ntawm lub duav ncig rau cov neeg laus nruab nrab [1]. Cov adiposity ntau dhau lawm yuav luag dhau los ua tus qauv, thiab cov xwm txheej hauv kev kuaj mob ntshav qab zib tau taug qab cov ntaub ntawv rog rog nrog kev ncua 15-20 xyoo vim muaj kev puas tsuaj loj heev los ntawm kev ua haujlwm hyperglycemia thiab cuam tshuam cov tshuaj insulin hauv cov ntaub so ntswg [2].

Tsuas yog 6.8 feem pua ​​​​ntawm cov neeg laus hauv Asmeskas tau muaj kev noj qab haus huv cardiometabolic zoo tshaj plaws hauv 2018 [3], qhov teeb meem tseem ceeb uas tau coj los rau hauv kev tsom mus rau ib zaug ntxiv los ntawm kev sib raug zoo ntawm metabolic noj qab haus huv thiab kev pheej hmoo ntawm mob hnyav COVID-19 cov txiaj ntsig cuam tshuam nrog kev tiv thaiv kab mob. -kev kho mob tsis zoo uas ua rau muaj kev mob ntsws (15 feem pua) thiab kab mob hnyav (5 feem pua) hauv cov neeg tsis tau txhaj tshuaj [4]. Qhov kev sib koom ua ke ntawm cov adiposity ntau dhau thiab cov kab mob tiv thaiv kab mob tsis zoo tam sim no tau pom thoob ntiaj teb, raws li 50-60 feem pua ​​​​ntawm cov pej xeem raug cais raws li cov rog lossis rog, thiab 9-12 feem pua ​​​​ntawm cov ntshav qab zib, hauv Europe [5], Middle East, thiab Gulf cheeb tsam [6], thiab East Asia [7].

Txawm hais tias plaub qhov kev pheej hmoo metabolic muaj qhov sib txawv ntawm cov kab mob pathophysiological, o, thiab oxidative kev nyuaj siab yog cov hauv nruab nrab hauv lawv txoj kev loj hlob [8-10]. Cov xeev metabolic cuam tshuam ncaj qha rau cov cim cim ntawm cov mob qis qis thiab cuam tshuam nrog kev tiv thaiv kab mob hauv cov ntaub so ntswg xws li rog, siab, txiav, thiab vasculature [11]. Lub cev tiv thaiv kab mob hauv lub cev (granulocytes thiab myeloid hlwb) tso cai rau cov lus teb sai sai rau kev raug mob lossis kev kis kab mob los ntawm kev ua kom cov qauv lees paub receptors; Txawm li cas los xij, nws qhov kev daws teeb meem tau qeeb qeeb hauv cov xeev metabolic tsis zoo.

Lub cev tiv thaiv kab mob hloov pauv (B thiab T lymphocytes) nyob rau hauv lem tseem ceeb heev nyob ntawm lub cev tsis muaj zog tiv thaiv kab mob rau kev nthuav qhia antigen thiab receptor-mediated activation, txwv tsis pub muaj peev xwm tswj tau zoo rau cov tshuaj tiv thaiv autoimmune. Hauv cov ntaub so ntswg, cov txheej txheem no zoo li tau khaws cia los ntawm cov ntaub so ntswg macrophages, nrog rau cov ntaub so ntswg macrophages paub tab tau los ntawm embryonic precursors noob nyob rau hauv qhov chaw ua ntej yug thiab nws tus kheej-renewed [12].

Kev ua tsis tiav ntawm kev tswj hwm cov metabolism hauv homeostasis ua rau lub xeev tsis zoo metabolic uas tso siab rau cov ntaub so ntswg nyob hauv macrophages kom nthuav tawm qhov mob [13]. Kev nthuav dav ntawm cov ntaub so ntswg adipose thiab ectopic cia ntawm triglycerides hauv daim siab, nqaij, thiab txiav txiav kuj ua tiav los ntawm cov tshuaj tiv thaiv hauv zos uas tso cai rau kom muaj zog perfusion thiab hloov kho cov ntaub so ntswg nruj [14]. Qhov no tau ua tiav los ntawm kev kho mob ntev ntawm cov teeb meem nyuaj uas suav nrog vasoactive amines (histamine thiab serotonin), eicosanoids-lipid mediators uas txhais tau hais tias pro-inflammatory (prostaglandins thiab thromboxanes) los yog anti-inflammatory (leukotrienes, lipoxins, resolvins) polarization, thiab. cytokines nrog cov teebmeem polarization zoo sib xws. Ib pawg tseem ceeb ntawm cov tshuaj molecules uas ua rau cov lus teb rau cov tshuaj tiv thaiv zoo li suav nrog TNF- , IL-1 /IL-6/IL-17, IL-18/INF- /MCP -1 [15], thiab cov tub txib ntawm kev ua kom ntev (NF-κB, COX-2, iNOS) [16]. Tam sim no nws tsis paub meej txog qhov xwm txheej ntawm qhov ua rau muaj kev cuam tshuam dab tsi dictates hom neeg nruab nrab induced.

Qhov xwm txheej no yog qhov nyuaj ntxiv los ntawm kev hloov pauv ntawm ob txoj kev sib raug zoo ntawm kev nplua nuj thiab ntau haiv neeg ntawm microbiota uas nyob hauv qhov chaw mucosal ntawm txoj hnyuv lossis lub ntsws, thiab cov ntaub so ntswg tiv thaiv kab mob [17]. Ib qho evolutionary mus kom ze rau kev tswj cov ntaub so ntswg kev ncaj ncees thiab noj qab nyob zoo metabolism yog sensing lub effector molecules (enzymes / substrates, receptors / ligands) los ntawm sequestrated hlwb uas ib txwm tsis overlap spatially, raws li pom nyob rau hauv lub nto epithelium, vascular endothelium, qab daus daim nyias nyias (epithelial- mesenchymal kev twb kev txuas), thiab plasma daim nyias nyias [13]. Kev sib dhos ntawm NALP3 inflammasome nyob rau hauv cov lus teb rau toxin intracellular ATP / cov tshuaj lom los ntawm kev ua kom cov macrophage purinoceptors [18], nrog rau kev sib txawv ntawm txoj hnyuv T hlwb hauv teb rau cov metabolites secreted los ntawm commensal microbial zej zog [19], qhia dual kev tswj ntawm cov metabolic. raws li txoj cai thiab kev saib xyuas ntawm qhov sib npaug zoo ntawm kev tiv thaiv kab mob thiab kev ua siab ntev hauv plab hnyuv.

Thaum kawg, lwm qhov sib txawv hauv kev sib raug zoo ntawm metabolic thiab kev tiv thaiv kab mob yog khoom noj. Cov zaub mov ua tiav niaj hnub ua tiav cov kev ua haujlwm tseem ceeb hauv kev tsim cov qoob loo thiab kev tsim lub neej zoo, thiab kev nyab xeeb ntawm cov khoom noj niaj hnub los xij. Qhov no tau ua tiav, txawm li cas los xij, ntawm qhov poob ntawm ntau yam phytonutrients tseem ceeb suav nrog kev noj zaub mov fiber ntau, micronutrients (vitamin thiab cov zaub mov tseem ceeb), thiab phytochemicals xws li phenolic metabolites [20]. Mineral malnutrition tshwj xeeb tshaj yog dav tab sis nyuaj rau kom muaj nuj nqis. Kev txo qis ntawm cov nqaij nruab deg, kev hloov pauv ntawm thaj chaw keeb kwm ntawm cov khoom noj, ntau yam tshiab, txoj hauv kev agroecological ntawm kev ua liaj ua teb thiab khaws cia cov av, thiab kev hloov pauv ib puag ncig yog ib feem ntawm lub luag haujlwm rau kev txo qis [21]. Lub luag haujlwm tseem ceeb ntawm cov zaub mov ua ib feem ntawm kev noj qab haus huv raws li nws siv rau kev noj qab haus huv thiab kev tiv thaiv kab mob tau txhawb kev tshawb fawb rau hauv kev hloov pauv ntawm cov cellular metabolism, feem ntau tsav los ntawm mitochondrial tsis ua haujlwm los tsim cov metabolic tsis sib xws, uas ua rau muaj kev mob thiab lub zog sib npaug. Cov cheeb tsam no yog qhov tseem ceeb ntawm kev tshuaj xyuas tam sim no.

2. Kev mob plab thiab metabolic tsis ua haujlwm

Inflamation yog ib qho physiological teb rau adverse stimuli, uas tej zaum yuav yog lub cev, tshuaj, los yog lom. Cov lus teb ib txwm ua rau kev rov qab los ntawm homeostasis thiab apoptosis ntawm malfunctioning lossis necrotic hlwb los ntawm macrophages. Nyob rau hauv cov txheej txheem no, macrophages tau ua kom ua kom muaj polarization ntawm ob lub xeev tsis sib xws, M1 lossis classical (pro-inflammatory), thiab M2 lossis lwm txoj hauv kev (pro-resolution) phenotype [22]. Ntxiv nrog rau kev tiv thaiv kab mob, M2 macrophages tshem tawm cov hlwb apoptotic thiab txo qis cov lus teb rau IL-4, IL-10, IL-13, thiab TGF- signaling [23].

Yog hais tias qhov tsis txaus siab stimuli tsis nruab nrab thiab tshem tawm, lossis yog tias cov hlwb apoptotic inflammatory tsis tshem tawm ntawm cov ntaub so ntswg, cov txheej txheem inflammatory txuas ntxiv mus, thiab cov mob ntawm cov mob ntev lossis autoimmunity tuaj yeem txhim kho nrog kev nrhiav T lymphocytes thiab tsim cov lymphoid. infiltrates hauv cov ntaub so ntswg metabolic [24] Cov txheej txheem no tshwj xeeb tshaj yog tshwm sim nyob rau hauv lub xeev metabolic ntawm morbid rog uas yog tus cwj pwm los ntawm kev ua kom tsis tu ncua ntawm lub cev tiv thaiv kab mob uas ua rau mob hnyav [25]. Kev txhawb nqa M2 lub xeev ntawm cov ntaub so ntswg-cov neeg nyob hauv macrophages yuav yog ib qho kev nthuav qhia kom txo tau cov kab mob inflammatory mediators thiab yog li txo cov kab mob metabolic cuam tshuam nrog kev mob ntev.

2.1. Inflamation nyob rau hauv Obesity

Kev rog dhau yog qhov tsis txaus ntseeg hauv ntau yam kab mob metabolic. Cov lipids ntau dhau hauv kev ncig, txawm tias lawv yog kev noj haus lossis kev txiav txim siab caj ces, ua rau hyperplasia, kho dua tshiab, thiab hypertrophy ntawm cov ntaub so ntswg adipose, thiab ua rau muaj roj ntau ntxiv raws li kev hloov mus rau lub zog ntxiv. Cov txheej txheem no muaj kev cuam tshuam loj heev, thiab qhov mob yog txuas rau txhua theem ntawm kev hloov pauv hauv metabolic. Metabolic tsis ua hauj lwm feem ntau pom ua ke nrog cov qib qis hauv zos o, tsis muaj cov insulin receptor signaling, thiab metabolic homeostasis cuam tshuam [26]. Txawm li cas los xij, kev koom tes meej ntawm tus neeg macronutrients (carbohydrates, rog, proteins) rau kev loj hlob ntawm rog thiab pro-inflammatory metabolic xeev tsis tau tsim.

Thaum muaj kev pom zoo dav dav uas nce qib ntawm fructose-muaj carbohydrates, saturated long-chain fatty acids, thiab branched-chain amino acids cuam tshuam kev noj qab haus huv ntawm metabolic, cov kev xav ntawm lawv lub luag haujlwm sib txawv yog polarized heev. Qhov no yog qhov tseem ceeb los ntawm feem ntau pom zoo U-zoo li lub koom haum ntawm kev pheej hmoo ntawm kev tuag thiab kev noj zaub mov carbohydrate, nrog rau cov ntaub ntawv kis mob los ntawm kev kawm PURE ntawm ib qho huab [27] thiab Blue Zone Diets ntawm lwm [28]. Cov kev tsis sib haum xeeb no tshwm sim los ntawm cov kev txwv tsis sib xws ntawm cov txheej txheem kev noj zaub mov ib leeg, thiab tsis muaj peev xwm los txheeb xyuas qhov kev tshawb pom nrog cov khoom noj sib xyaw ua ke. Piv txwv li, thaum cov protein yog diluted nyob rau hauv cov zaub mov los ntawm kev nkag tau yooj yim digestible carbohydrates thiab rog nyob rau hauv daim ntawv ntawm cov zaub mov ua tiav, protein "leverage" ua rau cov calorie ntau ntau, ua rau nce qib ntawm rog rog thiab kab mob metabolic [29].

Nyob rau theem molecular, cov txheej txheem tau sib kho hauv ib feem los ntawm kev nce de novo lipogenesis hauv daim siab, txo cov roj oxidation hauv mitochondria, tsub zuj zuj ntawm cov tshuaj lom ceramides thiab diacylglycerides, thiab ua kom mTOR uas thaum kawg degrade cov insulin receptor substrate -1 ( IRS-1) substrate thiab ua rau muaj kev ua haujlwm tsis zoo ntawm cov ntaub so ntswg-sensitive insulin [30]. Hauv kev sib tshooj zoo kawg li, qhov tsis zoo hauv IRS-1 substrate tsav cov proinflammatory phenotypes ntawm lub hom phiaj cov ntaub so ntswg [31]. Zoo ib yam li metabolic mediators, inflammatory cytokines zoo li TNF-, IL-6, thiab IL-1 kuj tseem cuam tshuam rau txoj kev taw qhia cov tshuaj insulin uas ua rau cov tshuaj insulin-tiv thaiv metabolic [32]. Ob leeg IL-6 thiab TNF- txhawb kev tsim cov kab mob siab ntawm C-reactive protein (CRP), uas yog ib qho tseem ceeb ntawm cov tshuaj reactant rau cov mob hnyav, uas tseem nce ntxiv hauv cov neeg rog rog. Qhov no ntxiv txhawb cov txheej txheem ntxiv, kho phagocytosis, thiab tswj kev mob hauv cov ntaub so ntswg [33].

Cytokines, endothelial adhesion molecules, thiab chemotactic mediators nyob rau hauv cov ntaub so ntswg adipose pib los ntawm ob qho tib si adipocytes, nrog rau cov neeg nyob hauv lossis cov macrophages uas nkag mus rau hauv cov ntaub so ntswg [34]. Cov teeb liab no tseem ua rau lwm txoj hauv kev molecular, hu ua inflammasome, hauv cov hlwb myeloid uas kho qhov kev loj hlob thiab tso tawm ntawm IL-1 thiab IL-18 los ntawm macrophages [35]. Cov neeg xa xov liaison muaj kev cuam tshuam hauv zos ntawm adipocytes thiab lwm cov kab mob hauv lub cev (xws li neutrophils, B hlwb, thiab T hlwb), thiab ncig hauv thaj chaw, uas lawv cuam tshuam rau lub siab thiab cov leeg pob txha. Hauv daim siab, qhov no txhais tau tias muaj kev nkag mus ntxiv nrog cov neeg nyob hauv Kupffer hlwb thiab monocyte-derived recruited hepatic macrophages [36], thaum lub cev nqaij daim tawv tau nce pro-inflammatory M1 macrophage infiltration [37].

2.2. Mob ntshav qab zib

Kev sib raug zoo ntawm kev tiv thaiv kab mob thiab carbohydrate metabolism yog bidirectional, encompassing ob qho tib si o lub luag hauj lwm nyob rau hauv lub pathogenesis ntawm metabolic ntshawv siab thiab cuam tshuam ntawm metabolic mob, nrog rau inflammatory signaling, nyob rau hauv lub cev tiv thaiv kab mob [38]. Ntawm cov kab mob pathophysiological, hom 2 mob ntshav qab zib mellitus (T2D) feem ntau tshwm sim los ntawm peripheral insulin tsis kam thiab kev qaug zog / kev puas tsuaj ntawm insulin-tsim pancreatic beta hlwb [39]. Cov kev hloov pauv no tseem cuam tshuam nrog kev ntxhov siab oxidative siab, uas ua rau muaj kev cuam tshuam ntxiv ntawm polyol, hexosamine, thiab protein kinase C (PKC) txoj hauv kev, nrog rau kev nce hauv kev tsim cov khoom siab tshaj glycation kawg (AGEs) [40] . Qhov tseeb, nce oxidative kev nyuaj siab tau ua rau muaj kev pheej hmoo loj tshaj plaws rau cov mob ntshav qab zib microvascular feem ntau, suav nrog nephropathy, retinopathy, thiab neuropathy tom qab theem ntawm T2D. Qhov tseem ceeb, hauv cov neeg mob ntshav qab zib, qhov no tsis tu ncua nce oxidative kev nyuaj siab ua rau qis-qib pathological o [40].

Ntau cov cim ntawm qhov mob tau nce siab hauv cov neeg mob ntshav qab zib, suav nrog cov lej leukocyte, IL-6, TNF- , thiab CRP [41]. Zoo ib yam li kev rog dhau, TNF- ua rau cov kab mob metabolic perturbation hauv cov neeg mob ntshav qab zib mellitus los ntawm kev ua kom cov tshuaj insulin los ntawm kev ua kom IκB kinase (IKK), c-Jun aminoterminal kinase (JNK), thiab inhibitory phosphorylation ntawm IRS -1 ntawm Ser 307 [42. ]. Kev sib raug zoo ntawm kev rog thiab insulin tsis kam yog ua piv txwv los ntawm qhov tseeb tias kev poob qis ntawm 5-15 feem pua ​​​​ntawm lub cev qhov hnyav tshaj 3-10 lub hlis yog txaus los txhim kho -cell muaj nuj nqi thiab insulin rhiab heev nyob rau hauv tag nrho cov tseem ceeb metabolically active ntaub so ntswg: daim siab, pob txha pob txha, thiab rog [43] Nws kuj tau lees paub ntev tias cov kev kho mob tiv thaiv kab mob ua rau txo qis cov tshuaj insulin raws li pom nrog salicylic acid [44], salicylates [45], lossis tshuaj aspirin [46], zoo li ntawm inhibition ntawm κB hauv NF-κB inflammatory pathway. Inflammasome-activated IL-1 thiab IL-18 yog cov cytokines loj cuam tshuam rau kev loj hlob ntawm kev rog- thiab ntshav qab zib muaj feem xyuam rau cov tshuaj insulin, thiab qee qhov kev tsis sib haum xeeb tau tshaj tawm rau IL-6 thiab qis qis. STAT txoj kev [47].

2.3. Inflammation nyob rau hauv Gastrointestinal Disorders

Lwm qhov kev sib cuam tshuam ntawm cov kab mob hauv plab hnyuv, microbiota hauv plab hnyuv lumen, thiab kev tiv thaiv tus tswv tsev, uas muaj kev cuam tshuam loj heev, tsis ntev los no tau hais tias muaj kev cuam tshuam rau cov kab mob metabolic [48]. Lub plab hnyuv sawv cev yog ib qho tseem ceeb ntawm lub cev tiv thaiv kab mob uas tswj kev tiv thaiv homeostasis los ntawm kev txhawb nqa kev ncaj ncees ntawm txoj hnyuv epithelial barrier thiab paub txog cov zaub mov thiab microbial antigens. Cuam tshuam ntawm epithelial teeb meem tshwm sim thaum ob npaug (lub plab lossis txoj hnyuv los yog ploj zuj zus los tso cai rau kev nce qib kev noj haus kom muaj kev nkag mus rau cov khoom noj thiab cov microbial metabolites ntawm paracellular thauj txoj kev [50]

Qhov no tsim ib qho tshwj xeeb antigen nthuav qhia ib puag ncig uas nyob rau hauv ib txwm muaj kev tshwj xeeb epithelial microfold (M) hlwb paub txog luminal antigens thiab nthuav tawm lawv mus rau mononuclear phagocytes (dendritic cells thiab macrophages) thiab B hlwb kom ua rau cov antigen-specific secretory IgA, nrog rau cov txheej txheem IgG. kev tsim kho [51]. Hauv tib neeg, cov cheeb tsam no feem ntau nyob hauv thaj chaw deb ntawm txoj hnyuv me (ileum) qhov twg microbial loads pib nce [52].

Qhov no tso cai rau kev ua kom raws sij hawm thiab kev sib txawv ntawm cov effector thiab kev tswj hwm Th hlwb feem ntau ntawm IL-10 thiab TGF- signaling los suppress cov inflammatory teb ntawm B thiab T hlwb pib los ntawm ib txwm zaub mov, commensal microbes, thiab ib puag ncig antigens [53] . Cov txheej txheem epithelial kuj tau nthuav tawm ntau tus naj npawb tseem ceeb ntawm tsev neeg iab saj receptors (TAS2R, 25 cov tswv cuab hauv tib neeg) uas tsis txhawb nqa qhov kev hnov ​​​​qab hauv plab, tab sis hloov pauv, muab ib puag ncig chemosensing los kuaj thiab teb rau cov khoom noj khoom haus thiab cov tshuaj microbial. thiab hloov kho lawv qhov nqus [54].

Ntxiv nrog rau ectopic lipid tsub zuj zuj thiab mob o nyob rau hauv cov ntaub so ntswg tseem ceeb, cov metabolic ntau dhau kuj txhawb o ntawm cov ntaub so ntswg. Raws li qhov sib txawv ntawm lub plab ua haujlwm sib txawv hauv kev zom zaub mov thiab kev nqus cov as-ham, cov txiaj ntsig kev noj qab haus huv ntawm cov kab mob plab inflammatory yog qhov sib txawv heev. Nyob rau hauv ib txwm lub xeev, lub duodenum txhawb kev zom cov zaub mov nrog pancreatic thiab kua tsib secretions, nrog rau cov hlau, calcium, thiab magnesium nqus. Lub jejunum absorbs feem ntau cov as-ham, vitamins, thiab minerals.

Lub ileum reabsorbs bile acids thiab kua dej, thiab txoj hnyuv ua kom tiav cov kua dej thiab electrolytes. Qhov kev sib cais ua haujlwm no yog ib feem ntawm cov kev tshwm sim sib txawv uas cuam tshuam nrog kev mob plab hnyuv, raws li kab mob celiac feem ntau cuam tshuam rau duodenum / jejunum, Crohn tus kab mob yog nyob rau hauv lub ileum thiab kis mus rau txoj hnyuv, thiab ulcerative colitis cuam tshuam feem ntau txoj hnyuv pib ntawm lub qhov quav. Vim li no, thawj cov ntxhia tsis txaus hauv cov neeg mob celiac yog hlau, calcium, magnesium, thiab rau qib qis zinc, tooj liab, thiab selenium [55].

Mineral malabsorption hauv Crohn cov neeg mob yog qhov sib txawv tab sis feem ntau suav nrog hlau, calcium, magnesium, thiab zinc [56]. Cov neeg mob ulcerative colitis tsis tshua muaj kev cuam tshuam rau cov pob zeb hauv av tab sis xav tau ntau cov zinc, tooj liab, thiab selenium los txhawb qhov txhab kho [57]. Cov kev hloov pauv ntawm cov kab mob epithelial barrier muaj nyob rau hauv tag nrho cov IBD tej yam kev mob thiab nthuav tawm raws li muaj zog xau-flux ntawm cov dej thiab cov kuab tshuaj uas ua rau kom siab antigen nthuav qhia, cov ntaub so ntswg o, thiab raws plab [58].

3. Immune Cell Metabolism thiab Metabolic Reprogramming

Lub cev tiv thaiv kab mob muaj ntau hom hlwb hauv nws lub xeev ruaj khov, uas ua haujlwm nyob rau hauv ntau lub sijhawm los teb cov kab mob, o, thiab kev hloov pauv hauv metabolic fluxes. Cov lus teb no suav nrog ntau qhov kev hloov pauv hauv txoj hauv kev hloov pauv cov teeb liab thiab cov noob qhia cov tes hauj lwm los ua cov haujlwm tsim nyog xws li kev tsim cov cytokines, cov ntaub so ntswg kho cov enzymes, cov neeg nruab nrab, thiab cov pa roj carbon dioxide, kom muaj peev xwm tsiv teb tsaws los ntawm cov ntaub so ntswg thiab / lossis kev faib cov cellular thiab proliferation. Cov kev hloov pauv no tau txais kev txhawb nqa los ntawm kev hloov pauv sai sai ntawm cov txheej txheem metabolic uas muab lub cev tiv thaiv kab mob nrog lub zog thiab bio-precursors kom cuam tshuam nrog kev tiv thaiv kab mob. Cellular bioenergetics, yog li ntawd, ua hauj lwm raws li ob qho tib si sensor thiab lub hauv paus effector ntawm lub cev tiv thaiv kab mob, thiab qhov no yuav tshwm sim ntau dua nyob rau hauv pathological metabolic xeev.

3.1. Inflamed Tissue yog Metabolically txwv ib puag ncig

Cellular metabolism koom nrog lub network ntawm biochemical cov tshuaj tiv thaiv uas siv cov as-ham thiab microelements los tsim lub zog, redox sib npaug, thiab macromolecules tshwj xeeb rau hom cell thiab kev ua haujlwm. Qhov no feem ntau ua tiav ua ntej ntawm glycolysis hauv cytosol thiab tom qab mitochondrial oxidative phosphorylation nyob rau hauv lub xub ntiag ntawm oxygen. Txawm li cas los xij, cov cell proliferating sai sai xws li cov qog thiab activated immune cells xav tau cov khoom siv hluav taws xob sai thiab ua tiav lawv los ntawm kev txo qis lawv cov metabolic efficiency thiab cia siab rau ze li ntawm qhov ceev glycolytic tshwm sim hauv cytosol.

Qhov no tso cai rau lawv tawm tsam lwm lub hlwb thiab cov ntaub so ntswg rau cov as-ham thiab microelements tseem ceeb rau lawv txoj sia nyob [59]. Aerobic glycolysis thiab pentose phosphate pathways yog lub ntsiab metabolic hom ntawm activated M1 macrophages, neutrophils (ua pa tawg thiab chemotaxis), iNOSexpressing dendritic hlwb, lymphocytes (effector T hlwb, LPS-stimulated B lymphocytes) thiab natural killer cells. Xwb, qhib lub cev tiv thaiv kab mob rau kev daws teeb meem ntawm qhov mob xws li M2 macrophages thiab kev tswj T hlwb cia siab rau oxidative phosphorylation los ntawm fatty acid oxidation es tsis txhob [60].

Kev muaj sia nyob ntawm lub cev tiv thaiv kab mob hauv lub cev tsis muaj zog nyob hauv ib puag ncig yog nyob ntawm kev sib tw ntawm cov piam thaj thiab cov lus qhia ntawm cov khoom thauj mus los ntawm lub xov tooj ntawm tes. Vim li no, ntau cov kab mob pro-inflammatory ua rau tsawg kawg ntawm kev hloov pauv, tab sis feem ntau lub xeev ntev ntawm insulin tsis kam nyob rau hauv cov ntaub so ntswg. Qhov no tau pom nyob rau hauv cov neeg mob sepsis [61], hlawv raug mob [62], thiab cev xeeb tub [63].

Qhov ua rau muaj cov piam thaj ntau ntxiv rau aerobic glycolysis muab cov biosynthetic precursors tseem ceeb rau kev sib txuas ntawm nucleotides, amino acids, thiab lipids ntawm cov cell loj hlob sai thiab proliferating. Cov kev hloov pauv hauv metabolic tau txhawb nqa ib feem los ntawm kev sib cuam tshuam ntawm glycolytic enzymes xws li GAPDH nrog kev txhais ntawm IFN- thiab IL-2 mRNA los xyuas kom meej tias tsis muaj kev txwv tsis pub muaj kev cuam tshuam ntawm cov teeb liab pro-inflammatory thaum glycolysis yog upregulated [64], nrog rau kev ua haujlwm ntawm glycolytic regulators xws li HIF-1 nyob rau hauv cov xwm txheej ntawm microenvironment hypoxia [65].

3.2. Metabolic Reprogramming thaum ua kom lub cev tiv thaiv kab mob

Kev xaiv ntawm cov txheej txheem metabolic ua rau lub cev tiv thaiv kab mob hloov mus rau lawv cov kev ua haujlwm, tab sis tib lub sijhawm, cov txheej txheem metabolic ntawm tus tswv tsev ncaj qha cuam tshuam rau phenotype thiab kev ua haujlwm ntawm lub cev tiv thaiv kab mob. Ob peb cov zaub mov tseem ceeb rau kev hloov pauv txaus ntawm kev so thiab qhib lub xeev ntawm lub cev tiv thaiv kab mob, kev ua haujlwm ntawm tus nqi-txheej enzymes hauv txoj hauv kev biochemical, thiab cov txheej txheem hloov pauv lub luag haujlwm rau kev ua kom lub hom phiaj ntawm kev nthuav qhia tes hauj lwm (Daim duab 1).

3.2.1. Neutrophils

Neutrophils yog ib tug subpopulation ntawm granulocytes (leukocytes) ntau nyob rau hauv cov ntshav thiab tsis tshua muaj nyob rau hauv cov ntaub so ntswg noj qab nyob zoo. Cov kab mob tiv thaiv kab mob no yog ib qho ntawm cov kev hloov pauv ntxov tshaj plaws uas nthuav tawm cov kab mob pro-inflammatory los ntawm kev tso tawm ntawm elastase 2, TNF- , thiab MCP-1 [47]. Neutrophils phagocytose khib nyiab, txhawb nqa angiogenesis, thiab tso cai rau cov ntaub so ntswg nthuav thiab kho. Lawv haus cov pa oxygen tsawg heev thiab vam khom feem ntau ntawm aerobic glycolysis los tsim ATP. Lub siab flux los ntawm txoj kev glycolytic thaum ua kom ua haujlwm yog channeled ntawm pentose phosphate txoj hauv kev los tsim NADPH thiab superoxide anions (oxidative tawg). Neutrophils kuj tswj qee qib ntawm fatty acid oxidation thiab glutaminolysis [66].

3.2.2. Mast Cells

Mast cells yog lwm chav kawm ntawm cov ntaub so ntswg uas nyob hauv hematopoietic hlwb uas yog cov teebmeem loj ntawm IgE-mediated allergies, tab sis kuj ua rau lub hlwb, plab hnyuv, thiab cov ntaub so ntswg adipose. Lawv tau dhau mus rau theem pib degranulation thiab lig-theem ua kom los ntawm kev tso tawm histamine, leukotrienes, TNF- , thiab Th2-txuas cytokines xws li IL-4, IL-6, IL{{7} }, thiab IL-13. Ob qho tib si oxidative phosphorylation thiab glycolysis tshwm sim yog qhov tseem ceeb rau kev tsis haum tshuaj sai, thaum glycolysis yog lub zog tseem ceeb rau kev ua kom tsis muaj IgE [67].

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