Oxidative Stress, Dysfunctional Energy Metabolism, Thiab Destabilizing Neurotransmitters Hloov Cov Cerebral Metabolic Profile nyob rau hauv ib tus nas qauv ntawm Simulated Heliox Saturation Diving rau 4.0 MPa Ⅱ

Cov txheej txheem rho tawm cov ntaub so ntswg

Cov txheej txheem rho tawm ntawm cov polar metabolites los ntawm cov qauv ntaub so ntswg yog ib qho kev hloov me me raws li qhia [18]. Preweighed cov ntaub so ntswg khov tau thawed rau ntawm cov dej khov thiab tom qab ntawd raug rau cov neeg kho tshuab homogenization nyob rau hauv cov dej khov-txias HPLC-qib methanol-chloroform-dej hnyav system (400 μL, 400 μL, thiab 285 μL, feem, ntawm 100 mg ntawm lub hlwb) siv cov ntaub so ntswg homogenizer (Precellys 24, Bertin Technologies, Villeurbanne, Fabkis). Cov txiaj ntsig homogenates tau khaws cia rau hauv dej khov rau lub sijhawm 30 min thiab tom qab ntawd centrifuged ntawm 12, 000 xg rau lub sijhawm 10 min ntawm 4˚C. Tom qab ntawd tus supernatant ntawm txhua tus qauv raug tshem tawm thiab lyophilized kom tau cov hmoov uas muaj cov polar metabolites hauv lub tshuab ziab khaub ncaws (FD-1A-80, BIOCOOL, Suav). Txhua cov qauv hmoov tau rov ua dua tom qab nrog 550 μL PBS tsis muaj 0.1 feem pua ​​​​TSP, thiab tag nrho cov qauv tom qab ntawd tau muab sib xyaw ua ke thiab centrifuged ntawm 12, 000 xg rau lub sijhawm 20 min ntawm 4˚C. Ib qho aliquot ntawm 500 μL ntawm supernatant raug xa mus rau hauv 5.0 mm-inch NMR raj (Norrel, UK). Lub hauv paus ntsiab lus ntawm kev rho tawm cov protein nyob hauv cov qauv cortex yog raws li tau piav qhia yav dhau los uas tsis muaj kev hloov kho. Qhov tseeb ntawm cov qauv cortex tau muab nchuav rau hauv homogenization tsis haum (HEPES 25 mmol / L, pH 7.4, MgC12 5 mmo1 / L, DTT 2 mmol / L, EDTA 1.3 mmol / L, EGTA 1 mmol / L, 0.1 feem pua ​​Triton X-100, aprotinin, pepstatin A thiab leupeptin 10 ug/ml txhua) thiab homogenized manually hauv da dej khov. Cov sib tov tau centrifuged ntawm 1,000 xg rau ib lub sij hawm ntawm 10 min ntawm 4˚C, thiab cov supernatant tau siv rau cov quantified protein concentrations siv Bradford test.

Nyem qhov no Kom Paub Cistanche Anti-Oxidation Function

Kev ntsuam xyuas biochemical

Ib qho kev sib tw, kev sib tw enzyme-linked immunosorbent assay (ELISA) tau siv nrog cov khoom siv tshuaj ntsuam xyuas kom muaj nuj nqis ntawm metabolic enzymes Na-KATPase thiab AChE thiab cov neurotransmitters DA, E, NE, 5HT, thiab GABA. ELISA kuj tau txiav txim siab qib SOD, MDA, thiab GPx hauv cov ntaub so ntswg cortical nrog cov khoom siv tshuaj ntsuam raws li cov chaw tsim khoom cov lus qhia.

NMR ntsuas

Kev ua kom muaj txiaj ntsig zoo ntawm cov ntaub so ntswg metabolites tau ua tiav los ntawm kev siv cov txheej txheem tshuaj ntsuam raws li cov kua ua kua Bruker Avance-III NMR spectrometer nruab nrog lub siab-rhiab heev cryogenic sojntsuam ua haujlwm ntawm zaus ntawm 600. 17 MHz rau 1 H soj ntsuam ntawm 298 K. Ib qho dej-suppressed ib-dimensional 1 H ZGPR (TOPSPIN version 3.0, Bruker Biospin) pulse sequence (RD-90˚-ACQ) tau siv rau tau txais NMR cov ntaub ntawv rau txhua tus qauv. Plaub qhov kev soj ntsuam dummy thiab 128 ntu raug kaw rau hauv lub sijhawm sau ntawm 32 K cov ntaub ntawv cov ntsiab lus siv qhov dav dav ntawm 20 ppm nrog kev so ncua ntawm 10.0 s thiab lub sijhawm tau txais ntawm 2.73 s. Ib qho exponential kab-broadening muaj nuj nqi ntawm 0.3 Hz thiab xoom-filling rau 64 K cov ntaub ntawv cov ntsiab lus tau siv rau tag nrho cov dawb induction decays (FIDs) ua ntej Fourier transformation. Ntxiv ob-dimensional NMR cov tswv yim nrog pulsed teb gradient correlation spectroscopy (gCOSY) thiab 2D homonuclear tag nrho correlation spectroscopy (TOCSY) tau ua hauj lwm siv cov txheej txheem pulse cov kev pab cuam ntawm cov qauv xaiv kom paub meej tias cov tshuaj ua haujlwm hloov. Ib qho kev hloov pauv hloov pauv tsis tu ncua rau cov qauv xa mus tas li tau siv rau hauv txhua qhov kev nrhiav tau.

Kev txheeb xyuas thiab kev pom zoo ntawm metabolite

NMR cov cim qhia raws li qhov chaw ntawm ib tus neeg resonances ntawm lub spectra tau txheeb xyuas hauv Chenomx NMR Suite v. 8.4 software pob (Kev ntsuas version). Kev lees paub ntawm qee qhov kev ua haujlwm metabolite tau ua los txiav txim siab txog kev hloov pauv tshuaj, kev sib txuas tsis tu ncua thiab ntau cov qauv ntawm cov metabolites raws li cov ntaub ntawv ntawm scalar couplings rho tawm los ntawm 1 H–1 H COSY, 1 H–1 H TOCSY, pej xeem NMR databases xws li COLMAR thiab Human Metabolome Database (HMDB), thiab cov ntaub ntawv [18, 19].

Multivariate statistical tsom xam

Cov txheej txheem ua ntej siv rau kev ua ntej txhua 1D 1 H NMR spectrum yog tib yam li tau piav qhia hauv peb txoj haujlwm dhau los [20]. Lub 1 H NMR spectra tau phased thiab lub hauv paus-kho siv MestReNova (Mestrelab Research, SL, Spain), thiab thaj tsam spectral ntawm txhua metabolite tau muab tso rau hauv ib lub thoob. Lub resonances ntawm cov organic hnyav teeb liab thiab cov seem H2O / HOD teeb liab cheeb tsam raug tshem tawm nyob rau hauv tag nrho cov 1D 1 H NMR spectra. A 0.{{30}}03 Hz tus txheej txheem thoob thiab normalization rau cov lej ntawm cov spectral intensity multiplied los ntawm 10000 tau siv nyob rau hauv tag nrho cov spectra. Tsuas yog cov khoom loj tshaj plaws nyob rau hauv ib lub ncov tau raug xaiv rau cov kauj ruam tom ntej kom tsis txhob muaj kev txhais lus tsis raug ntawm cov metabolites vim muaj kev sib tshooj. Tom qab ntawd, ib lub thoob ntawm 47 metabolites tau muab rho tawm thiab raug rau kev txheeb xyuas cov ntaub ntawv sib txawv thiab ntau yam. Kev txheeb xyuas kev ntxub ntxaug los ntawm tus thawj tswj hwm kev tsom xam (PCA) thiab kev txheeb xyuas kev ntxub ntxaug los ntawm ib feem tsawg squares-discriminant analysis (PLS-DA) thiab orthogonal projections rau latent structures discriminant analysis (OPLS-DA) tau ua los ntawm SIMCA-P ntxiv rau 14.0 software pob (Umetrics , Umeå, Sweden) scaled rau unit variance data. PCA thiab PLS-DA cov qhab nia tau piav qhia nrog thawj thiab thib ob lub ntsiab lus tseem ceeb (t[1], t[2]), thaum OPLS-DA cov qhab nia tau siv t[1] thiab cov khoom siv orthogonal (rau [1] ]). Cov tsis muaj Q2 (cum), R2Y (cum), thiab R2X (cum) raug xam los ntsuas qhov muaj zog ntawm cov qauv kev ntxub ntxaug tawm tsam overfitting [21]. Raws li tau hais dhau los, qhov kev ntsuas tus nqi zoo ntawm Q2 � 0.4 yog suav tias yog tus qauv txhim khu kev qha. Lub xya lub tswv yim hla kev siv tau zoo thiab kev sim ntsuas 200 zaug nrog thawj cov khoom siv tau siv los tiv thaiv tus qauv overfitting thiab ntxiv validate qhov kev ntseeg tau thiab kev ntseeg siab ntawm cov qauv. Yog hais tias Q2 regression kab muaj qhov cuam tshuam tsis zoo thiab Q2 qhov tseem ceeb haum rau ntawm qhov taw tes sab laug yog ntau dua li tag nrho Q2 qhov tseem ceeb ntawm cov ntsiab lus ntawm txoj cai nyob rau hauv qhov kev sim permutated, tus qauv OPLS-DA tau tsim muaj zog [22]. Lub neej ntawd 10-fold cross-validation lub tswv yim tau siv los tiv thaiv tus qauv overfitting. Feem ntau, kev soj ntsuam zoo (Q2) � 0.4 yog suav tias yog tus qauv txhim khu kev qha, raws li tau piav qhia dhau los. Cov kev sib raug zoo coefficients (r) thiab VIP qhov tseem ceeb tau muab rho tawm los ntawm OPLS-DA qauv tau siv los txheeb xyuas cov metabolites uas ua rau muaj txiaj ntsig zoo rau kev sib cais ntawm ob pawg. Tsis tas li ntawd, kev hloov pauv ntawm cov metabolites ntawm pawg tau suav nrog kev ua haujlwm. IA / IB, qhov twg IA thiab IB sawv cev rau qhov txiaj ntsig ntawm cov metabolite hauv cov pab pawg A thiab B, feem. Daim phiaj tshav kub thiab cov kab kos duab tau npaj los pab txhawb kev nkag siab ntawm metabolite variations ntawm pab pawg.

Univariate txheeb cais ntawm metabolite integrals

Lub thoob nruab nrab ntawm cov metabolites nyob rau hauv txhua pab pawg yog qhia raws li qhov nruab nrab ± standard deviation (SD). Kev tsom xam Univariate kuj tau ua tiav siv ANOVA (kev tshuaj xyuas ntawm qhov sib txawv). Kev txheeb xyuas qhov sib txawv ntawm cov pab pawg tau raug soj ntsuam los ntawm qhov tsis sib xws t-test ntawm ob lub tails tom qab kev hloov pauv hauv GraphPad Prism V 8.4.3 software (Graph Pad Software Inc., San Diego, CA, USA). Kev txheeb cais tseem ceeb sib txawv tau txhais los ntawm qhov tseem ceeb ntawm p (< 0.05). According to the three criteria, including an absolute value of r greater than 0.50, a value of VIP greater than 1.0, and a p-value less than 0.05, the bucket variables with one of three features will be selected as discriminatory variables. Because more than one bucket value was listed from the same metabolite, two or more discriminative variables arising from the same metabolite will be present in the discriminatory panel. Selection will be carried out based on VIP rankings, and only the variables from the same metabolites with the highest VIP values were therefore selected as discriminatory metabolite level features, which will be included in the next-step analysis.

Qhov system statistical metabolic correlation tsom xam thiab hierarchical pawg tsom xam

Pearson txoj kev sib txheeb coefficient suav thiab hierarchical pawg soj ntsuam tau ua raws li cov txheeb ze ntawm cov metabolites hauv R Studio (Version 1.4.1717) nrog cov ntawv me. Rau txhua pab pawg, qhov sib txheeb matrix tau piav qhia hauv daim duab qhia pixel raws li tau piav qhia hauv cov ntaub ntawv [21]. Luv luv, rau txhua qhov sib txawv hauv ib pab pawg, kev sib raug zoo nrog p qhov tseem ceeb tsawg dua 0.05 tau suav tias yog qhov tseem ceeb ntawm kev sib raug zoo thiab tau khaws cia los tsim cov kev sib raug zoo kawg los piav qhia txog kev sib raug zoo ntawm cov metabolites hauv cov pab pawg thiab cuam tshuam metabolic kev sib raug zoo ntawm pab pawg. Cov squares redder qhia txog kev sib raug zoo ntau dua. Cov squares bluer qhia txog kev sib raug zoo ntau dua. Cov squares dawb qhia txog kev sib raug zoo tsis muaj qhov tseem ceeb. Kev tshuaj xyuas ntawm cov kab mob hauv nruab nrog cev feem ntau cuam tshuam thiab kev sib txuas lus tau hu ua cov neeg teb rau HSD tau ua tiav siv MetaboAnalyst 3.0 cuab yeej. Rau txoj kev tshawb xyuas topology ua tiav, Rattus norvegicus (rat) mammalian pathway tsev qiv ntawv raug xaiv. Txoj hauv kev no kuj tau siv los muab kev kwv yees ntawm txoj kev cuam tshuam, qhov kev tshawb pom tsis tseeb (FDR), thiab p qhov tseem ceeb.

Cov txiaj ntsig Cortical biochemical indexes los ntawm HSD thiab CON pawg

Txhawm rau txheeb xyuas qhov cuam tshuam ntawm metabolic ntawm HSD ntawm lub hlwb cov ntaub so ntswg, biochemical tsis, nrog rau lub zog metabolism hauv metabolic enzymatic kev ua ub no ntawm Na-KATP, ACHE, thiab LDH, cov neurotransmitters ntawm DA, E, NE, 5HT, thiab GABA, thiab tusoxidative stress-related proteinsntawmSOD, MDA, thiab Gpx hauv ipsilateral cortex cov ntaub so ntswg ntawm HSD thiab CON nas kuj tau txiav txim siab (Table 1). Piv nrog rau pawg tswj hwm, qib ntawm DA, E, NE, thiab MDA tau nce ntxiv, thaum cov ntsiab lus ntawm Na-KATP, ACHE, LDH, 5HT, GABA, SOD, thiab Gpx tau txo qis hauv HSD qauv. Qhov txwv ntawm kev tshawb nrhiav cov khoom siv tshuaj ntsuam uas siv rau hauv txoj haujlwm tam sim no tau teev nyob rau hauv S3 Table nyob rau hauv cov ntaub ntawv ntawm cov ntaub ntawv ntxiv.

Table 1. Kev ntsuas qhov ntsuas ntawm biochemical tsis tau ntsuas hauv cortex cov ntaub so ntswg CON thiab HSD tsiaj los ntawm ELISA nrog cov khoom siv ntsuas. (txhais tau tias ± SD). qhia txog qhov tseem ceeb.

Cov metabolites pom nyob rau hauv 1 H NMR spectra ntawm lub paj hlwb kuaj

Fig 3 qhia peb tus neeg sawv cev 1 H NMR spectra los ntawm cortex (Fig 3A), hippocampus (Fig 3B), thiab striatum (Fig 3C) ntawm HSD nas. Ntau yam ntawm cov metabolites tseem ceeb tau txheeb xyuas raws li 1 H NMR cov ntaub ntawv ntawm cov qog nqaij hlav hlwb, thiab lawv yog cov organic acid anions (lactate (Lac), malonate (Maln), succinate (Suc), malate (Mal), fumarate (FMA). ), 2-hydroxybutyrate (2-HB), acetate (Ace), formate (For), taurine (Tau), ascorbate (Asc), 2-hydroxybutyrate (2HIB)), amino acids Leucine (Leu), isoleucine (Ile), valine (Val), alanine (Ala), glycine (Gly), tyrosine (Tyr), phenylalanine (Phe), aspartate (Asp), glutamine (Gln), glutamate (Glu) , threonine (Thr), serine (Ser), lysine (Lys), asparagine (Asn), neurotransmitters (-aminobutyrate (GABA), creatine (Cre), adenosine triphosphate (ATP), adenosine monophosphate ( AMP), phospholipid ntsig txog metabolites (Ophosphoethanolamine (PEA), O-phosphocholine (Pcho), sn-glycero-3- phosphocholine (GPC)), thiab lwm yam (myo-inositol (MI), nicotinamide adenine dinucleotide (NAD ntxiv) ), nicotinu ric acid (Nic), N-acetylaspartate (NAA), nicotinamide-adenine-dinucleotide phosphate (NADP ntxiv), UDP-N-galactose (UDPGa), uridine (Uri), uracil (Ura), cystidine (Cyt) , uridine 5'- monophosphate (UMP), inosine 5'-monophosphate (IMP), inosine (Ino), choline (Cho), car nitine (Car), glutathione (GSH). S1 Table qhia cov ncauj lus kom ntxaws txog cov haujlwm metabolite.

Cov txheej txheem metabolic tshwm sim los ntawm kev txheeb xyuas metabolic

PCA, ib qho kev tshawb nrhiav thiab tsis ncaj ncees rau kev tsom xam ntawm 1 H NMR spectra los ntawm txhua lub hlwb rho tawm thoob plaws lub hlwb sib txawv, tau ua ntej los qhia txog cov ntsiab lus metabolic uas tau tsav los ntawm hyperbaric raug rau 400 msw Heliox saturation ib puag ncig. PC1 vs. PC2 scatting plot tau los ntawm PCA (S1A–S1C Fig) ntawm ib lub thoob cov ntaub ntawv qhia txog qee yam kev ntxub ntxaug nrog qee qhov sib tshooj ntawm ob qhov kev faib tawm. Kev soj ntsuam xyuas ntawm PLS-DA (S1A'–S1C' Fig) thiab OPLS-DA (Fig 4A–4C) qauv qhia pom meej meej kev ntxub ntxaug ntawm cov metabolic profiles ntawm pawg. Fig 4 qhia cov qhab nia ntawm OPLS-DA qauv rau thaj tsam cortex (A), thaj tsam hippocampus (B), thiab thaj tsam striatum (C), qhia meej kev ntxub ntxaug ntawm pawg HSD thiab kev tswj hwm. Qhov kev piav qhia siab hloov pauv thiab qhov zoo ntawm qhov kev twv ua ntej tau cuam tshuam los ntawm qhov tseem ceeb ntawm R2X thiab Q2 (S1A'–S1C' Fig, Fig 4A–4C) thiab permutation test plots (Fig 4'-4C'A) qhia txog robustness ntawm generated saib xyuas qauv. Cov kev sib raug zoo coefficient (r) tau muab rho tawm los ntawm S-line cov phiaj xwm, qhov tseem ceeb sib txawv hauv qhov projection (VIP), thiab p-tus nqi los ntawm cov kev ntsuam xyuas nonparametric univariate tau sau los ntsuam xyuas cov metabolites tseem ceeb hauv lub luag haujlwm rau cov qauv kev ntxub ntxaug hauv chav kawm. Yog li ntawd, ua tau raws li ib qho ntawm peb cov txheej txheem (qhov tseeb tus nqi ntawm r ntau dua 0.50, tus nqi ntawm VIP ntau dua 1.0, nrog rau p tus nqi tsawg dua 0.05), peb tau xaiv ib lub vaj huam sib luag ntawm cov metabolites tseem ceeb. (Table 1) lub luag haujlwm rau kev sib cais ntawm pawg CON thiab HSD. Hauv Table 1, fold-hloov qhov tseem ceeb ntau dua 1 qhia txog qib nce hauv pawg HSD, thaum fold-hloov qhov tseem ceeb tsawg dua 1 qhia txog qib qis hauv pawg HSD. Qhov nruab nrab SD qhov tseem ceeb ntawm kev ntxub ntxaug metabolites tau teev nyob rau hauv S2 Table. Siv cov hierarchical pawg tsom xam ntawm metabolites thiab qhov nruab nrab txoj kev sib txuas, cov qauv tsim hluav taws xob (Fig 5A-5C) nrog dendrograms tso cai rau kev pom zoo dua ntawm peb lub hlwb thaj tsam metabolic hloov pauv los ntawm hyperbaric raug nyob rau hauv ib puag ncig helium oxygen-saturated.

Cov kab mob metabolic tau pom nyob rau hauv ntau thaj tsam ntawm lub hlwb ntawm HSD nas

Cov lus hais saum toj no ntau yam kev txheeb xyuas thiab kev txheeb xyuas tsis sib xws siv lub thoob qhov siab ntawm cov metabolites hauv cov pab pawg sib txawv tau muab lub raj ua haujlwm zoo los txheeb xyuas cov metabolites kev ntxub ntxaug uas qhia txog qhov muaj peev xwm ntawm cov kab mob metabolic cuam tshuam nrog HSD cov xwm txheej. Elevated AMP, FMA, Nic, thiab Phe thiab txo qis hauv Ala, Asn, Tsheb, Cho, Cyt, GABA, GSH, Ino, Lac, Pcho, Phe, Tyr, Ura, thiab Uri tau pom nyob rau hauv cov ntaub so ntswg cortex ntawm HSD. pawg piv nrog pawg CON (Fig 5A, Table 1). Lub caij no, hauv hippocampus, Ala, GSH, Lac, Uri, Cyt, GABA, Tyr, thiab Ura kuj txo qis thiab AMP nce hauv pawg HSD, raws li lawv tau ua hauv cortex. Ntxiv mus, lub upregulated Thr thiab downregulated Gly, ATP, Tau, Imp, Suc, Asc, thiab DMA tau qhia nyob rau hauv hippocampus extracts ntawm HSD pab pawg neeg txheeb ze rau cov tswj (Fig 5B, 5D, Table 1). Piv nrog rau pawg CONS, cov ntsiab lus ntawm Cyt, GABA, Ura, Cho, thiab Thr kuj tau txo qis raws li lawv tau ua hauv cortex thiab hippocampus. Tsis tas li ntawd, nce qib ntawm branched-chain amino acids (BCAAs, suav nrog Leu, Ile, Val), thiab Lys thiab txo qis ntawm Gln, NAA, NAD ntxiv, NADP ntxiv, Asp, ntau cov metabolites ntawm ATP, Tau, IMP, thiab Suc, uas kuj txo qis hauv hippocampus, thiab lwm ob lub metabolites, Ino thiab Pcho, uas kuj txo qis hauv cortex, tau pom nyob rau hauv cov ntaub so ntswg striatum ntawm HSD pab pawg nas (Fig 5C, 5D, Table 1). Xws li ntau cov metabolites ib txwm qhia txog kev cuam tshuam ntawm molecular txoj hauv kev nrog complexity thiab ntau haiv neeg. Qhov tseem ceeb ntawm lub thoob qhov tseem ceeb ntawm cov metabolites kev ntxub ntxaug tau raug txheeb xyuas, thiab cov ntaub ntawv tseem ceeb ntawm kev hloov pauv ntawm lawv cov concentrations ntawm heliox-saturation-hyperbaric-exposed thiab tswj pawg tau sau tseg hauv S2 Table thiab Table 2 rau peb lub paj hlwb.

Daim duab 4. Orthogonal ib feem tsawg kawg squares discriminant tsom xam (OPLS-DA) cov qhab nia thiab permutation test plots uas cais cov nyhuv ntawm 400 msw heliox-saturation exposure ntawm 1H NMR spectra los ntawm cov pab pawg tswj nyob rau hauv lub cortex (CONC, n=8, HSDC, n=8, A thiab A') (R2X=0.38; Q2=0.46), hippocampus (CONH, n {{12}) }, HSDH, n=8, B thiab B') (R2X=0.37; Q2=0.43), thiab striatum (CONS, n=8, HSDS, n=8, C thiab C') (R2X=0.39; Q2=0.40). Qhov tseem ceeb ntawm Q2 parameter hauv OPLS-DA cov qhab nia cov phiaj xwm, uas yog sib npaug los yog ntau dua 0.40, ua ke nrog Q2 qhov tseem ceeb ntawm qhov taw tes sab laug hauv cov qauv permutated tau ntau dua li tag nrho cov khoom tsim nyog Q2 ntawm cov ntsiab lus raug (permutation xeem 80 zaug), qhia tias cov qauv tsim OPLS-DA tau siv tau.

Pcho, uas kuj txo qis hauv cortex, tau pom nyob rau hauv cov ntaub so ntswg striatum ntawm HSD pab pawg nas (Fig 5C, 5D, Table 1). Xws li ntau cov metabolites ib txwm qhia txog kev cuam tshuam ntawm molecular txoj hauv kev nrog complexity thiab ntau haiv neeg. Qhov tseem ceeb ntawm lub thoob qhov tseem ceeb ntawm cov metabolites kev ntxub ntxaug tau raug txheeb xyuas, thiab cov ntaub ntawv tseem ceeb ntawm kev hloov pauv ntawm lawv cov concentrations ntawm heliox-saturation-hyperbaric-exposed thiab tswj pawg tau sau tseg hauv S2 Table thiab Table 2 rau peb lub paj hlwb.

Fig 5. Heatmap thiab statistical correlation plots derived from the bucket values ​​of the discriminatory metabolites from the cortex (A, A', HSDC tests lies in the top panel and CONC lies in the low panel), hippocampus (B, B', HSDH pawg lus dag nyob rau hauv lub vaj huam sib luag sab sauv thiab CONH nyob rau hauv lub vaj huam sib luag qis), thiab striatum (C, C', HSDS cov qauv pw hauv lub vaj huam sib luag sab saud thiab CONS nyob rau hauv qab vaj huam sib luag) cov ntaub so ntswg ntawm HSD thiab CON nas. Cov metabolites ntawm lub tshav kub yog tsim los ntawm hierarchical pawg raws li tag nrho cov zoo sib xws hauv cov qauv qib. Venn daim duab (D) qhia txog cov metabolite sib tshooj ntawm HSDC-CONC, HSDH-CONH, thiab HSDS-CONS kev sib piv.

Kev txheeb xyuas ntawm metabolite

Kev sib raug zoo ntawm lossis ntawm cov metabolites yog qhov nyuaj heev hauv daim duab 5A'-5C'. Rau lub zog metabolites, qhov kev sib raug zoo rau Lac vs Ala hauv HSDC, AMP vs IMP hauv HSDH, ATP vs Pcho hauv HSDS, Suc vs GABA / Gln / Tyr / NAA hauv HSDS, thiab cov kev sib raug tsis zoo rau Lac vs Thr thiab GSH vs. Suc hauv HSDH, Suc vs Val hauv HSDS muaj nyob rau hauv cov phiaj xwm metabolite. Rau cov neurotransmitters, qhov kev sib raug zoo rau GABA vs Tsheb hauv HSDC, GABA vs Cho hauv CONH, thiab GABA vs Suc / Ino / Gln hauv HSDS muaj nyob hauv cov phiaj xwm metabolite correlation. Qhov kev sib raug zoo tsis zoo rau GABA vs FMA hauv CONC thiab GABA vs NAA / Ura / NADP ntxiv rau hauv CONS tau tshwm sim hauv cov phiaj xwm metabolite. Rau cov txheej txheem metabolitesoxidative kev nyuaj siab, covkev sib raug zoofor GSH vs Asn in the HSDC and the CONC, Tau vs Lac in the HSDH, Tau vs Suc/Ala in the CONH, the negative correlations for GSH vs Suc in the HSDH, Tau vs Thr in the HSDH are present in the metabolite correlation cov phiaj xwm.

Kev txheeb xyuas cov txheej txheem metabolic

Kev txheeb xyuas ntau txoj hauv kev suav nrog kev txheeb xyuas txoj hauv kev txhim kho thiab txoj hauv kev cuam tshuam los ntawm txoj hauv kev topology tau nthuav tawm cov ntaub ntawv tseem ceeb ntawm HSD-induced modulations rau ntau txoj hauv kev metabolic. Cov qhab nia cuam tshuam rau txoj hauv kev, suav nrog tus lej nrhiav pom tsis tseeb (FDR) thiab p qhov tseem ceeb, tau piav qhia hauv daim duab 6. Txoj hauv kev tau suav tias muaj txiaj ntsig zoo yog tias p tus nqi qis dua 0.05; cov profiled metabolites (hits) txheeb ze rau tag nrho cov metabolites ntawm txoj kev (match raws li txoj cai) yog siab tshaj 1; thiab cov qhab nia cuam tshuam (qhia txog qhov cuam tshuam ntawm cov metabolites cuam tshuam loj hauv txoj hauv kev raws li network topology ntsuas ntawm txheeb ze nruab nrab ntawm qhov nruab nrab) tau siab dua 0. Txoj hauv kev hauv cortex (Daim duab 6A) nrog cov txiaj ntsig zoo tshaj plaws ntawm metabolic yogphenylalanine, tyrosine, thiabtryptophan biosynthesis>phenylalanine metabolism> pyrimidine metabolism > alanine, aspartate, thiab glutamate metabolism. Txoj hauv kev hauv hippocampus (Fig 6B) nrog qhov cuam tshuam loj tshaj plaws hauv metabolic yog phenylalanine, tyrosine, thiab tryptophan biosynthesis> glutathione metabolism> glycine, serine, thiab threonine metabolism> purine metabolism> pyrimidine metabolism> alanine, aspartate, thiab glutamate metabolism. . Txoj hauv kev hauv striatum (Daim duab 6C) nrog qhov cuam tshuam loj tshaj plaws hauv metabolic yog alanine, aspartate, thiab glutamate metabolism> nicotinate thiab nicotinamide metabolism> purine metabolism.

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