Uremic Toxins Thiab Protein-Bound Therapeutics hauv AKI Thiab CKD: Cov Ntaub Ntawv Txog Hnub Nyoog Ⅱ

4. Qhov cuam tshuam ntawm PBUTs Accumululation

4.1. Muaj Peev Xwm Mechanism ntawm Uremic Toxin Retention Involved in AKI to CKD Progression

Lub peev xwm txheej txheem ntawm IS-induced aggravated AKI rau CKD kev vam meej yog paub zoo, muaj kev nce TGF- signaling, oxidative kev nyuaj siab, inflammatory teb, ER kev nyuaj siab, thiab senescence [43-47]. IS induces ROS tiam thiab tubular cell DNA puas ua rau tubular cell voj voog raug ntes nyob rau theem G2M. Kev ncua ntev ntawm qhov raug ntes G2M theem hauv tubular hlwb kuj tau lees paub tias yog ib qho ntawm cov txheej txheem kho tsis zoo, uas ua rau AKI hloov mus rau CKD [48].

ORGANIC tshuaj ntsuab rau lub raum mob

Myofibroblasts ua lub luag haujlwm tseem ceeb hauv kev tsim cov kab mob extracellular ntau dhau thiab tuaj yeem muab tau los ntawm kev ua kom lub raum interstitial fibroblasts, perivascular fibroblasts, thiab pericytes, myelin protein zero-Cre (P0-Cre) kab ntawv sau npe fibroblasts hauv lub raum fibrosis. tsiaj qauv [49–51]. Thaum raug PBUTs, fibroblasts ncaj qha qhib los ntawm IS lossis PCS stimulation los yog indirectly los ntawm tubular secreted TGF- ces ua rau myofibroblast activation thiab extracellular matrix deposition [52–54]. Chen et al. qhia tias qhov ncauj gavage ntawm IS precursor-indole nrawm AKI mus rau CKD kev nce qib hauv ER kev ntxhov siab-raws li [32]. Tsis tas li ntawd, ntau qhov kev tshawb fawb txhawb nqa lub tswv yim uas AKI thuam txhawb kev loj hlob ntxov ntxov [55,56]. Nws tsim nyog pom tias cov tshuaj tiv thaiv kev laus Klotho tau pom tias muaj qib qis hauv CKD cov ntaub so ntswg [57–59]. Lub hauv paus txheej txheem tau tshwm sim los ntawm Sun et al., nyob rau hauv uas IS thiab PCS tsub kom nce DNA methyltransferase qhia, uas ua rau klotho noob hypermethylation thiab suppresses klotho protein qhia [57,60]. Yog li, nws tau npaj siab tias PBUTs yuav yog qhov muaj feem cuam tshuam rau kev nrawm nrawm tom qab AKI.

4.2. PBUTs Retention ua rau muaj kev pheej hmoo ntawm kev kis kab mob hauv ntau lub cev tsis ua haujlwm

Ntxiv rau cov kev tshawb fawb yav dhau los uas qhia tau hais tias AKI muaj feem cuam tshuam nrog kev pheej hmoo siab dua ntawm qhov tshwm sim tsis zoo [61,62], kev tshawb fawb tam sim no tau qhia tias PBUTs hauv cov hlab ntsha hauv cov neeg mob AKI ua rau muaj kev cuam tshuam rau ntau lub cev, nrog rau cov kab mob plawv thiab mob ntsws [63,64]. Wu et al. qhia tau hais tias cov ntshav IS qib tau nce siab hauv cov neeg mob AKI thiab Shen li al. kuj pom nyob rau hauv UIRI nas qauv [65,66].

Accumulated IS impaired endothelial progenitor cell (EPC) muaj nuj nqi los ntawm oxidative kev nyuaj siab ua rau EPC senescence, inhibition ntawm proliferation, thiab apoptosis [65]. Ntxiv rau qhov endothelial cell dysfunction thaum lub sij hawm PBUT raug, nce IS thiab PCS qib yog txuam nrog plawv calcification nyob rau hauv cov neeg mob CKD [67]. Yog li, nws tau xav tias AKI kuj yog qhov muaj feem cuam tshuam rau kev txhim kho cov hlab plawv calcification. Txog kev koom tes ntawm PBUT thiab mob ntsws tom qab AKI, Yabuuchi li al. ua ob sab nephrectomy-induced IS tsub zuj zuj ntawm cov nas uas ua rau mob ntsws raug mob los ntawm kev txo qis hauv aquaporin -5 qhia, ib qho tseem ceeb thauj khoom hauv kev tswj lub ntsws homeostasis [68,69].

5. Diagnostic Value ntawm PBUTs nyob rau hauv AKI rau CKD Progression

sCr thiab BUN qib yog cov cim surrogate tam sim no siv los kuaj xyuas AKI [17]. Txawm li cas los xij, raws li tau hais tseg los ntawm cov ntshav creatinine tsub zuj zuj, AKI yuav tsis cuam tshuam txog kev raug mob ntawm tubular vim qhov sib txawv ntawm uremic toxins tshem tawm txoj kev, thiab qhov tsis muaj kev hloov pauv hauv sCr tsis paub tseeb tias tsis muaj kev raug mob ntawm tubular. Ntxiv mus, qhov tsis zoo tshwj xeeb ntawm sCr tuaj yeem nce siab vim kev noj zaub mov lossis tshuaj yeeb tshuaj uas ua rau lub cev tso tawm ntawm creatinine [70]. Yog li ntawd, nws tau lees paub dav dav tias cov cim no tsis yog qhov tshwj xeeb lossis muaj kev cuam tshuam hauv peb qhov kev kho mob [71]. Yog li ntawd, nrhiav pom lwm qhov kev ntsuam xyuas lub raum ua haujlwm tau zoo biomarker yog qhov teeb meem tshwm sim rau kev kuaj mob zoo dua.