Kev hloov pauv hauv Kev Txhais Lus Protein Thiab Carboxylic Acid Catabolic Txheej Txheem hauv Ntshav Qab Zib raum Kab Mob Ⅱ

3. Cov txiaj ntsig

3.1. Tibneeg Tej Yam

Lub raum ntaub so ntswgcov qauv los ntawm 18 cov ntsiab lus nrog DKD thiab 9 cov ntsiab lus siv yam tsis muajDKDtau txais thiab kawm (Table 1). Qhov nruab nrab hnub nyoog ntawm cov ntaub so ntswg tau yog 55.0 xyoo ntawm cov kev kawm nrog DKD thiab 50.0 nyob rau hauv cov ntaub ntawv nephrectomy siv. Cov kawm nrog DKD yog 61.1% poj niam thiab 27.8% yog Dub. Feem ntau cov neeg DKD muaj cov nodular glomerulosclerosis thiab ib nrab muaj ntau dua 80% effacement ntawm podocyte ko taw txheej txheem. Nephrotic ntau yam proteinuria tau pom nyob rau hauv 55.6% ntawm DKD kawm. Lub hauv paus eGFR yog 63.2 ± 26.2 mL / min. Cov ntsiab lus poob qhov nruab nrab ntawm 14.5 mL / min / xyoo ntawm eGFR nyob rau lub sijhawm ua raws, uas yog 47.7 lub hlis ntawm qhov nruab nrab. Raws li ib pab pawg neeg sib piv molecular, cuaj qhov piv txwv nephrectomy tau txais. Cov qauv no tau soj ntsuam los ntawm ib tus neeg dig muaglub raum pathologist(CP) thiab tsis qhiahistological pov thawjtshwj xeeb raumob ntshav qab zib raumkab mob; txawm li cas los xij, kho mob thiabcov ntaub ntawv pej xeemxws li haiv neeg, proteinuria, thiab eGFR tsis muaj.

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3.2. Differential Gene Expression thiab Pathway Analysis nyob rau hauv Diabetic Human Glomerulus thiab Proximal Tubule

Qhov sib txawv ntawm cov noob caj noob ces thiab kev txheeb xyuas txoj hauv kev tau ua nyob rau hauv DKD thiab cov pab pawg siv. Cov noob sib txawv (DEGs) tau txheeb xyuas nyob rau hauv laser microdissected glomeruli thiab cov tubules ze ze ntawm ob pawg (Supplemental Table S1; https://doi.org/10.6084/m9.figshare.14450190.v1, accessed 23 Lub Ib Hlis 2022). Paub glomerular markers tau down-regulated hauv DKD, suav nrog nephrin (NPHS1, 3-fold txo, p=1.0 × 10−4) thiab phospholipase C epsilon 1 (PLCE1, 2.{18} }fold txo, p=3.3 × 10−4 ). Ib yam li ntawd, cov cim tubular proximal suav nrog sodium-hydrogen ex-hloov cofactor 3 (PDZK1, 4.2-fold txo, p=1.9 × 10−5 ) thiab sodium-phosphate cotransporter (SLC34A1, 3.

Peb tau tshuaj xyuas txoj hauv kev txhawb nqa los ntawm kev txheeb xyuas kev sib txuas lus transcriptogram hauv tib neeg glomerulus thiab cov tubule ze ze ntawm DKD thiab cov qauv siv. Qhov kev tshuaj ntsuam no suav nrog qhov loj ntawm qhov sib txawv, qhov kev taw qhia ntawm cov nyhuv, theem ntawm qhov tseem ceeb, thiab qhov sib thooj ntawm cov protein-coding noob tau txiav txim raws li x-axis raws li paub txog kev sib cuam tshuam ntawm cov protein-protein. Txoj hauv kev zoo tshaj plaws ntawm glomerulus suav nrog GTPase-mediated signal transduction (p=4.3 × 10−6 ) thiab G-protein coupled receptor (GPCR) ligand binding (p=8.1 × 10− 6). Hauv cov tubule ze ze, txoj hauv kev sab saum toj yog Rhodopsin-zoo li receptors (p=4.1 × 10−6 ) thiab olfactory signaling (p=1.9 × 10−4 ). Hauv kev nthuav dav, txoj hauv kev ribosome (kev txhais lus) tau ua kom muaj txiaj ntsig hauv ob qho tib si glomerulus thiab cov tubule proximal (Daim duab 1). Daim ntawv teev tag nrho ntawm txoj kev tswj hwm qhov sib txawv yog suav nrog hauv Cov Lus Ntxiv S2; (https://doi.org/10.6084/m9.figshare.14450196.v1, nkag mus rau 23 Lub Ib Hlis 2022)

Table 1. Cov yam ntxwv kho mob ntawm cov qauv.

Txhawm rau txiav txim siab txog kev cuam tshuam rau txoj kev txhais lus txhawb nqa hauv DKD cov qauv, txoj hauv kev pom schematic ntawm KEGG txoj kev sib npaug, ribosome hsa03010, tau muab tso ua ke rau ob qho tib si glomerulus thiab proximal tubule. Cov noob nyob rau hauv kev txhais lus thiab cov metabolism ntawm cov amino acids thiab derivatives GO txoj hauv kev ua raws li txoj hauv kev ribosome KEGG nrog kev sib tshooj ntawm 130 thiab 87 ntawm 186 noob, raws li. Tag nrho cov kev qhia ntawm ribosomal noob tau nce-tswj nyob rau hauv ob qho tib si glomerulus thiab proximal tubules ntawm DKD kawm (Daim duab 2).

HERB CISTANCHE FOR diabetic kidney disease

3.3. Kev txhais lus hloov pauv hauv cov kab mob ntshav qab zib nas raum

Txhawm rau kom nkag siab zoo dua qhov tseem ceeb ntawm txoj kev txhim kho hauv tib neeg DKD biopsy cov qauv, peb tau nug qhov sib txawv ntawm tus nas db piv rau kev tswj hwm keeb kwm yav dhau los siv ntau RNA sequencing. Txoj kev tsom xam (thaum muaj hnub nyoog 9 lub lis piam) nruab nrab ntawm cov nas mob ntshav qab zib thiab cov kab mob tswj tau pom tias txoj hauv kev zoo tshaj plaws yog cGMP-protein kinase G signaling (p=2.0 × 10- 6) (Daim duab 3A). Ntawm cov kev nplua nuj yog kev txhais lus hais txog ribosome biogenesis (p=0.047), uas "overlapped" nrog tib neeg DKD txoj kev txhawb nqa dataset. Txhawm rau tshuaj xyuas ncaj qha rau qhov ua tau zoo ntawm kev nce transcription thiab qhia cov proteins tswj kev txhais lus, peb tau ua polyribosomal profiling ntawm ob lub raum los ntawm db thiab keeb kwm yav dhau los tswj cov nas. Qhov kev ntsuam xyuas no suav cov theem dav dav ntawm kev txhais lus raws li mRNA nyob los ntawm ribosomes. Polyribosomal profiling pom tau hais tias qhov polysome-rau-monosome cheeb tsam-hauv-qhov-khoov piv yog nce hauv cov nas mob ntshav qab zib (9.76) piv rau cov nas tswj (7.73, p <0.05 rau qhov sib txawv ntawm qhov sib piv), zoo ib yam nrog kev txhais lus thoob ntiaj teb ntau ntxiv hauv cov nas.raum hauv ntshav qab zib(Daim duab 3B).

HERB CISTANCHE FOR diabetic kidney disease