Ntu Ⅰ: Lub raum tuav ntawm Albumin—Los ntawm Kev Tshawb Nrhiav Thaum Ntxov mus rau Cov Ntsiab Lus Tam Sim No

Hu rau:joanna.jia@wecistanche.com/ WhatsApp: 008618081934791

Jakub Gburek, Bogusława Konopska thiab Krzysztof Goł ˛ab

1. Taw qhia

Albuminyog ib qho ntawm cov proteins uas pom tau ntxov tshaj plaws hauv lub cev. Nws tau piav qhia thawj zaug los ntawm Denis hauv xyoo 1840. Nws lub npe muab los ntawm Latin lo lus Albus (dawb) vim yog cov khoom ntawm dawb precipitate tsim nyob rau hauv ib puag ncig acidic. Cov protein no muaj ntau heev nyob rau hauv lub cev thiab muaj nyob rau hauv inter alia: plasma, lymph, cerebrospinal thiab extracellular kua. Nws plays ntau yam tseem ceeb physiological functions.Albumintso nyiaj ntau dua 50 feem pua ​​​​ntawm tag nrho cov plasma proteins, thiab nws cov ntsiab lus siab (45 g / L, 0.6 mM) txiav txim siab txog 80 feem pua ​​​​ntawm cov colloid osmotic siab ntawm cov ntshav plasma [1]. Nws yog lub luag haujlwm rau kev faib dej ntawm cov ntshav plasma thiab cov kua dej ntxiv, uas ua kom muaj kev saib xyuas ntawm cov ntshav hemodynamics thiab tiv thaiv o. Txoj haujlwm thauj khoom ntawmalbuminyog ib yam tseem ceeb. Qhov loj ntim ntawm kev faib tawm cuam tshuam nrog nws qhov yooj yim nkag mus los ntawm capillary epithelium ua rau ntau dua 60 feem pua ​​​​ntawm tag nrho cov pas dej ntawm cov protein no nyob rau hauv qhov chaw extravascular. Xws li ib tug loj nkag ntawmalbuminmus rau hauv cov kua dej interstitial tso cai rau nws sib cuag nrog feem ntau ntawm lub cev lub hlwb, ua rau nws yog ib tug zoo tagnrho cov cab kuj ntawm tsawg-molecular metabolites. Cov tshuaj endogenous thauj los ntawmalbuminmuaj xws li, inter alia: ntev-chain fatty acids, aromatic carboxylic acids, bilirubin, kua tsib acids, porphyrins, nitric oxide, thiab ions ntawm divalent hlau, xws li Co, Cu, Ni, Zn cations.AlbuminNws kuj yog ib qho protein uas khi cov cations ntawm cov hlau hloov pauv hauv cov dawb radical tiam, xws li Cu lossis Fe. Nws kuj yog tus cwj pwm los ntawm nws lub luag haujlwm tiv thaiv oxidative thiab ua rau lub complexation ntawm Cd, Hg, thiab V ions, uas yog ib qho tseem ceeb rau cov txheej txheem detoxification. Vim muaj cov pab pawg dawb-SHCys34,albuminper se yog ib qho antioxidant thiab ib qho tseem ceeb ntawm plasma antioxidative barrier [2]. Nws tseem tsim nyog hais tias thaum lub sij hawm ntev kev tshaib kev nqhisalbuminyog degraded los muab cov amino acids tseem ceeb rau macromolecular synthesis thiab lub zog tsim. Nyob rau hauv lub xeev ntawm protein deficiency, lub synthesis ntawmalbuminyog 2.5-fold ceev, thiab nws cov peev txheej raug txo los ntawm yuav luag 50 feem pua ​​[3,4].

cistanchekho tauraumkab mobtxhim kholub raum ua haujlwm

Xav txog qhov tseeb tiasalbuminplays lub luag haujlwm tseem ceeb hauv homeostasis, nws yog qhov tseem ceeb rau lub cev kom tswj tau nws cov ntshav plasma ib txwm muaj. Ib tug txo nyob rau hauvalbuminconcentration yog pom nyob rau hauv ntau yam metabolic ntshawv siab ntawm ntau yam etiologies. Tej zaum nws yuav yog qhov tshwm sim ntawm kev faib tawm tsis raug, piv txwv li ntawm pancreatitis, txo cov synthesis hauv daim siab cirrhosis, amino acid absorption disorders lossis noj cov zaub mov tsis muaj protein ntau; poob nyob rau hauv cov chav kawm ntawm enteropathy, kub hnyiab, cov txheej txheem phais, los yog nephrotic syndrome, raws li zoo raws li ceev catabolism nyob rau hauv o thiab mob cancer. Kev poob qis yog tshwm sim los ntawm ntau yam teeb meem loj cuam tshuam rau hauv nruab nrab paj hlwb, ua pa, thiab hlab plawv, nrog rau kev tsim ntawm edema, ua kom cov coagulation yam, hypotransfer rinemia, high-density lipoprotein (HDL) dyslipidemia, oxidative stress, thiab ntau yam. Cov kab mob metabolic cuam tshuam nrog nws txoj haujlwm thauj. Tsis tas li ntawd, nyob rau hauv cov xeev hypoalbuminemia, cov dawb pharmacologically nquag nquag feem ntawm cov tshuaj yog nce, uas yuav tsum tau txiav txim siab rau kev teeb tsa qhov kev pom zoo. Hyperalbuminemia yog ib yam mob uas tsis tshua muaj thiab tuaj yeem tshwm sim los ntawm lub cev qhuav dej lossis cov ntshav venous ntau dhau. Txawm li cas los xij, plasma ntau dhaualbuminqib tsis cuam tshuam nrog kev mob hnyav dua [5,6].

Intravenous kev tswj ntawmalbuminkev npaj nyob rau hauv lub xeev ntawm hypoalbuminemia ua rau sai, kho ib ntus ntawm oncotic siab thiab tiv thaiv hypovolemia. Yog li ntawd,albuminKev npaj tau siv, inter alia, hauv kev kho mob ntawm qhov kub hnyiab, mob ua pa tsis ua haujlwm, mob hemolytic mob hnyav hauv cov menyuam mos thiab cov neeg mob tom qab phais mob plawv [7,8]. Tsis tas li ntawd, vim nws lub peev xwm los khaws cia hauv cov ntaub so ntswg ntawm cov qog thiab qhov chaw inflammatory, kev tshawb fawb ntawm cov tshuaj raws li conjugates muaj.albumintau ua. Piv txwv li, tshuaj ua ke nrog exo- lossis endogenousalbumin, cross-linked nyob rau hauv daim ntawv ntawmalbuminmicro-thiab nanocapsules, nrog rau cov noob caj noob ces fusions ntawm cov tshuaj polypeptide, tau kuaj xyuas [9].

Yog li ntawd,albumincatabolism yog ib qho teeb meem tshawb fawb tseem ceeb hauv cov ntsiab lus ntawm pathophysiology thiab cov tshuaj cuam tshuam. Ib qho ntawm cov kabmob tseem ceeb koom nrog hauv cov txheej txheem no yog lub raum. Cov kab mob raum catabolism tuaj yeem ua rau tsis yog rau cov teeb meem cuam tshuam nrog hypoalbuminemia, tab sis kuj mus rau kev loj hlob ntawm nephrotic syndrome nyob rau hauv chav kawm ntawm albuminuria, thiab yog li ntawd mus rau qhov kawg ntawm lub cev tsis ua hauj lwm. Kev sib raug zoo ntawm cov proteinuria thiab lub raum tsis ua haujlwm yog qhov nyuaj thiab koom nrog cov xwm txheej pathological sib kho los ntawm chemokines rau interstitial o, mononuclear cell accumulation, thiab intrarenal activation ntawm ntxiv. Proinflammatory thiab profibrogenic cov cim qhia ua rau muaj kev raug mob hauv zos thiab cuam tshuam rau lub raum fibrosis. Raws li qhov tshwm sim, qhov depletion ntawm kev ua haujlwm nephrons tau pom [10]. Vim li no, qhov teeb meem no tau raug kev tshawb fawb dav dav rau ntau xyoo. Cov kev tshawb fawb uas tau ua dhau los ntawm kaum xyoo dhau los tau ua rau muaj txiaj ntsig zoo rau kev nkag siab ntawm cov txheej txheem molecular koom nrog hauv cov txheej txheem no, nrog rau qee qhov kev tsis sib haum xeeb cuam tshuam nrog lawv. Txoj kev tshawb no nthuav tawm cov txiaj ntsig ntawm kev tshawb fawb tshiab hauv daim teb no.

cistanche txiv neej cov txiaj ntsig

2. General Albumin Metabolism

2.1. Synthesis

Albuminyog tsim los ntawm polysomes ntawm ntxhib endoplasmic reticulum ntawm hepatocytes thiab secreted li preprotein. Thaum tsiv mus rau qhov du endoplasmic reticulum, lub teeb liab peptide raug tshem tawm. Kev ua tiav ntxiv tshwm sim ntawm txoj hauv kev secretory thiab koom nrog kev tshem tawm hexapeptide uas muaj nyob rau ntawm N-terminus ntawm cov molecule[11]. Tus nqi ntawmalbuminsynthesis yog 10-15g ib hnub twg, uas yog kwv yees li 10 feem pua ​​ntawm tag nrho cov protein synthesis nyob rau hauv daim siab. Ib qho me me ntawmalbumin(kwv yees li 2 g) yog khaws cia rau hauv daim siab, thaum feem ntau yog secreted rau hauv vascular qhov chaw. Lub pas dej plasma ntawm cov protein no suav nrog 30-40 feem pua ​​​​ntawm nws cov nyiaj tag nrho, thiab cov seem seem muaj nyob hauv daim tawv nqaij thiab cov leeg. Kwv yees li 5 feem pua ​​ntawmalbuminxau mus rau hauv qhov chaw extracellular, los ntawm qhov uas nws rov qab mus rau lub systemic ncig los ntawm txoj kev lymphatic [4]. Lub synthesis ntawmalbuminyog ib tug tas mus li txheej txheem uas yog tswj nyob rau theem ntawm transcription thiab pib ntawm kev txhais lus los ntawm txawv stimuli. Piv txwv li, lub synthesis yog intensified tom qab noj cov zaub mov thiab txo nyob rau hauv inter-noj lub sij hawm. Cov txheej txheem no tseem cuam tshuam los ntawm cov tshuaj hormones. Lub synthesis ntawmalbuminnce hauv hyperthyroidism thiab txo qis hauv hypothyroidism. Corticosteroids thiab insulin txhim kho kev tsim khoomalbuminnyob rau hauv cov neeg noj qab haus huv, thaum lub synthesis ntawm cov protein no yog inhibited nyob rau hauv mob theem teb. Kev txo qis ntawm cov poov tshuaj hauv cov hepatocytes txo cov nqi ntawmalbumintso tawm rau hauv kev, tab sis tsis inhibit cov protein synthesis nws tus kheej. Txawm li cas los xij, cov kev hloov hauv oncotic siab qhia txog qhov tseem ceeb ntawm kev siv ntawmalbuminsynthesis. Qhov tseebalbuminconcentration kuj tseem khaws cia vim qhov sib npaug catabolism pom nyob rau hauv tag nrho cov ntaub so ntswg [12].

2.2. Catabolism

Covalbumin covIb nrab-lub neej hauv plasma yog 19 hnub, thiab nws qhov kev puas tsuaj txhua hnub hauv tib neeg lub cev tsis pub tshaj 14g. Cov catabolism ntawm cov protein no tshwm sim feem ntau hauv cov leeg nqaij thiab tawv nqaij (txog 40-60} feem pua ​​​​o), thiab tshwj xeeb tshaj yog nyob rau hauv vascular endothelial hlwb ntawm cov ntaub so ntswg nyob rau hauv lub teeb ntawm kev tshawb fawb tsis ntev los no, nws ntseeg tau hais tias lub molecular mechanism ntawm internalization thiab kev thauj ntawmalbuminmus rau lub degradation organelles nyob rau hauv cov hlwb yog caveolin-dependent endocytosis nrog scavenger receptors gp18, gp30 thiab gp60 (albondin)[13-16]. Lub siab koom nrog hauv cov txheej txheem no kom tsawg dua (kwv yees li 15 feem pua). Ntxiv nrog rau vascular endothelial hlwb, hepatocytes kuj koom nrogalbuminnqa. Nws catabolism hauv parenchymal hlwb kuj tshwm sim los ntawm cov qauv txuam nrog caveolin [17,18]. Proteolytic degradation ntawmalbumintshwm sim tom qab lub internalization thiab fusion ntawm caveolae nrog lysosomes. Cov molecules tau tawg mus rau hauv cov amino acids dawb uas pub lub koom haum ntawm cov amino acids.

Muaj qee qhov pov thawj tias kev mob ntsig txog hypoalbuminemia yog qhov tshwm sim los ntawm kev ua kom muaj zog ntau dua los ntawm kev txo qis kev sib txuas. Oxidizedalbuminlos yogalbuminhloov nyob rau hauv lwm txoj kev yog tawg nyob rau hauv lub siab. Nyob rau hauv cov xeev inflammatory, cov txheej txheem no yog upregulated vim muaj zog capillary permeability thiab intensive flux ntawm plasma protein rau interstitium [19].

Albumincatabolism kuj tshwm sim hauv ob lub raum (kwv yees li 10 feem pua), txawm li cas los xij, cov txheej txheem molecular koom nrog rau lub raum.albuminturnover yog qhov tseem ceeb sib txawv. Tom qab glomerular filtration, cov protein yog internalized nyob rau hauv lub proximal tubules ntawm clathrin-dependent endocytosis nrog kev koom tes ntawm tandem ntawm macromolecular scavenger receptors - megalin thiab cubilin. Ces tusalbuminCov molecules raug lysosomal degradation thiab / los yog transcytosis, uas yuav tau tham nyob rau hauv kom meej nyob rau hauv cov tshooj hauv qab no.

cistanche txiv neej cov txiaj ntsig

3. Lub raum Albumin Catabolism

Lub raumalbumincatabolism suav nrog pom nyob rau hauv lub glomerulus, reabsorption nyob rau hauv proximal tubules, thiab intracellular degradation los yog ib feem ntawm transcytosis rau hauv cov hlab ntsha. Tsuas yog me me xwbalbumin, piv txwv li, txog li 100 mg ib hnub twg, yog tawm hauv cov zis. Nyob rau hauv cov ntaub ntawv ntawm kev puas tsuaj rau lub filtration barrier los yog dysfunction ntawm proximal tubules,albumintshwm nyob rau hauv cov zis nyob rau hauv cov concentrations uas yuav ntau tshaj 3 g ib hnub twg [20].

3.1. Glomerular Filtration ntawm Albumin

Lub permeability ntawm glomerular barrier txiav txim siab muaj pes tsawg leeg ntawm thawj filtrate. Nws yog tsim los ntawm peb txheej: ib qho innermost fenestrated endothelial cell txheej, glomerular qab daus daim nyias nyias, thiab ib txheej txheej ntawm podocytes nrog lawv interdigitating ko taw txheej txheem txuas los ntawm ib tug slit diaphragm. Cov yam ntxwv multilayer ntawm sieve ua rau lub pore maj mam txo qhov loj me. Nyob rau hauv xyoo tas los no, ua tsaug rau txoj kev loj hlob ntawm noob caj noob ces qauv, nws muaj peev xwm txheeb xyuas lub ntsiab Cheebtsam lub luag hauj lwm rau qhov no barrier kev ncaj ncees. Lub luag haujlwm tseem ceeb tshaj plaws yog tam sim no raug ntaus nqi rau qee cov qauv ntawm cov glomerular qab daus daim nyias nyias (GBM) (piv txwv li, collagen hom IV thiab laminin 2) thiab podocyte glycocalyx proteins (piv txwv li, podocin thiab nephrin) [21,22]. Txawm li cas los xij, kev ua haujlwm ntawm podocytes tsis txwv rau sieving. Nws tau raug pom tias tib neeg thiab tsiaj podocytes endocytosealbuminhauv vitro [23,24]. Cov ntaub ntawv kuj qhia tias podocytes ntshiab proteins los ntawm GBM ntawm transcytosis [25]. Cov kev tshawb fawb no qhia tias podocytes internalizesalbuminthiab lwm yam plasma proteins (xws li, IgG) thiab nyob rau hauv txoj kev no tiv thaiv glomerular filtration barrier (GFB) los ntawm clogging.

Kev ntsuas ntawm glomerular permeability yog glomerular sieving coefficient (GSC), uas yog qhov piv ntawm cov concentration ntawm ib qho molecule muab hauv thawj lim rau nws cov ntshav plasma concentration. Qhov degree ntawmalbuminpermeation yog cov ntsiab lus ua rau muaj ntau qhov kev tsis sib haum xeeb, thiab GSC qhov tseem ceeb tau txiav txim siab hauv ntau yam kev sim ua qauv sib txawv los ntawm peb qhov kev txiav txim loj.

Kev suav cov theoretical qhia tau hais tias lub pore txoj kab uas hla ntawm qhov barrier yog hais txog 4 nm thiab raug nqi tsis zoo vim yog cov ntsiab lus siab ntawm glycosaminoglycans. Yog li ntawd, qhov pom ntawm cov kab uas loj dua thiab / lossis cov uas muaj qhov nruab nrab tsis zoo yuav tsum yog qhov nyuaj. Nyob rau hauv cov nqe lus ntawm cov duab, lubalbuminmolecule zoo ib yam li lub ellipsoid nrog loj thiab me diameters ntawm 14 nm thiab 3.8 nm, raws li, thiab nws cov resultant nqi yog -15 (pI=4.5). GSC yuav tsum qis qis thiab qhov nruab nrab ntawm (5.10-4-7.10-4)[26,27]. Qhov concentration ntawmalbuminHauv cov ntshav plasma yog li 45 g / L, yog li nws cov concentration hauv thawj cov lim dej yuav tsum sib txawv ntawm 22 thiab 32 mg / L [28]. Cov txiaj ntsig no zoo ib yam li cov tau txais hauv kev soj ntsuam hauv cov neeg mob uas tsis tshua muaj kab mob cuam tshuamalbuminlub raum tuav lossis siv cov qauv kev sim tsiaj. Cov txiaj ntsig tau txais los ntawm kev siv cov txheej txheem micro-puncture ntawm cov seem tubule thaum ntxov nyob rau hauv cov nas noj qab haus huv (6.10-4) yog qhov zoo sib xws nrog cov qauv theoretical [27,29]. GSC ntawmalbuminxam los ntawm nws cov zis tso zis los ntawm cov neeg mob uas muaj Fanconi syndrome tus yam ntxwv los ntawm tubular albuminuria yog me ntsis qis dua qhov qis ntawm qhov ntsuas qhov ntsuas (8.0.10-5)[30]. Hauv qhov sib piv, GSC suav nrog cov zisalbuminconcentration hauv nas nrog pharmacologically inhibited tubular reabsorption yog me ntsis siab dua (3.3·10-4)[31]. Ntxiv mus, nyob rau hauv cov kev tshawb fawb ntawm lub raum cais perfused ntawm 8 degree, qhov twg tubular kev ua si yog kiag li inhibited vim tsis muaj fluidity ntawm lub cell membrane, GSC qhov tseem ceeb tau ntau dua (110-3)[32]. Cov kev tsis sib xws uas tau hais los saum no tuaj yeem piav qhia los ntawm cov kev txwv ntawm kev siv cov kev ntsuas. Piv txwv li, nrog kev siv cov cuab yeej micro-puncture, muaj kev pheej hmoo tias cov qauv sau tau tuaj yeem muaj cov kab mob plasma los ntawm cov hlab ntsha puas tsuaj thaum lub sij hawm pipette projection, thiab yog li ntawd nws tsis cuam tshuam qhov tseeb filtrate vim yog nqus sai heev ntawm cov protein nyob rau hauv. thawj ntu ntawm lub tubule proximal. Nyob rau hauv cov ntaub ntawv ntawm cov ntaub ntawv los ntawm cov neeg mob uas muaj Fanconi syndrome, nws yog tsis muaj peev xwm mus ntsuam xyuas qhov degree ntawm proximal tubule kev puas tsuaj thiab nws yuav tsum tau xav tias reabsorption ntawm cov proteins tsis yog tag nrho inhibited. Tib yam siv rau cov qauv nrog pharmacological inhibition ntawm reabsorption. Tsis tas li ntawd, cov ntaub ntawv los ntawm kev sim siv cov kab mob sib cais yog qhov nyuaj rau kev txhais vim yog qhov sib txawv ntawm hemodynamics dua li hauv vivo. Txawm hais tias qhov tsis sib xws hauv GSC qhov tseem ceeb tau txiav txim siab los ntawm cov txheej txheem sib txawv, feem ntau lees txais lub ntsiab lus ntau xyoo yog qhov pom ntawm glomerular.albuminyog qhov me me thiab yog tus cwj pwm los ntawm GSC qhov ntsuas hauv qab 1.10-3.

Cov txiaj ntsig tau txais los ntawm kev siv cov txheej txheem qis qis ntawm hauv situ ob-photon microscopies tau ua rau muaj kev tsis sib haum xeeb hauv xyoo tas los no. Qhov kev txiav txim siab GSC tau siab dua piv rau cov kev tshawb fawb yav dhau los (2-4.10-2). Fluorescent-labeledalbumintau txhaj tshuaj intravenously rau ntshav qab zib Munich-Wistar nas nrog nto glomeruli thiab ib txwm bulimia. GSC tau txiav txim siab los ntawm kev sib piv plasma fluorescence siv nyob rau hauv glomerular capillaries thiab thawj filtrate hauv Bowman qhov chaw. Cov txiaj ntsig zoo sib xws tau txais tsis hais txog qhov concentration thiab txoj kev sau npealbuminkev tswj hwm (bolus / infusion) 33]. Cov ntaub ntawv no zoo ib yam nrog cov kev tshawb fawb yav dhau los hauv nas, uas proteinuria raug ntxias los ntawm kev tswj hwm ntawm Puromycin aminonucleoside. Cov tshuaj no ua rau hypoalbuminemia tshwm sim ntau dua 60 feem pua ​​​​ntawm cov ntshav qab zibalbuminconcentration. Piv rau cov ntsiab lus noj qab haus huv, tsis muajalbuminreuptake nyob rau hauv txhuam ciam teb ntawm proximal tubule hlwb nyob rau hauv nas kis mus rau puromycin, uas ua rau kom nce nyob rau hauv lub raum.albuminexcretion Performance index kom siab dua 300 mg ib hnub twg [34]. Qhov tsis muaj reabsorption tau cuam tshuam nrog kev txo qis hauv kev qhia ntawm megalin, V-ATPase, thiab clathrin hauv apical ncej ntawm tubule [35]. Cov kws sau ntawv ntawm cov kev tshawb fawb saum toj no ntseeg tias glomerularalbuminfiltration yog ib txoj kev ua tau zoo heev, uas feem ntau yog raws li lub hauv paus ntsiab lus ntawm qhov chaw ruaj khov convective flow es tsis yog diffusion, thiab cov kev txwv uas tshwm sim los ntawm qhov loj ntawm covalbuminmolecule thiab cov yam ntxwv ntawm cov glomerular barrier tsis loj npaum li qhov xav tau. Raws li qhov tshwm sim, lawv hais tias albuminuria tsuas yog tshwm sim los ntawm qhov txawv txavalbuminreabsorption thiab tsis yog los ntawm kev puas tsuaj rau glomerular barrier raws li yav dhau los xav. Lwm tus qauv tau nthuav tawm hauv ob peb qhov kev tshuaj xyuas [36-38].

Kev xaiv ntawm glomerular barrier, uas yog txuam nrog tus nqi, tsis tau pom nyob rau hauv cov kev tshawb fawb yav dhau los [39,40]. Ib qho kev pom ntau ntxiv kuj tuaj yeem cuam tshuam nrog cov dawbalbuminpermeation los ntawm cov pores loj ntawm ib txoj kab uas hla ntawm 75-110 A, lub xub ntiag ntawm uas nyob rau hauv lub glomerular barrier yog pom zoo los ntawm Ohlson li al.[32] nyob rau hauv txoj kev tshawb no ntawm protein filtration nyob rau hauv ib tug cais perfused raum. Qhov tshwm sim ntawm xws li pores hauv vivo tau lees paub hauv kev tshawb fawb ntawm cov neeg mob Fanconi syndrome, uas muaj cov protein ntau loj, xws li transferrin lossis IgG, tau pom hauv cov zis [30].

Txawm li cas los xij, cov txiaj ntsig tau los ntawm Russo et al. [33] tau suav tias yog tsis ntseeg los ntawm cov zej zog kev tshawb fawb. Gekle [41] tau taw qhia tias thaum ob-photon microscopy txheej txheem tuaj yeem siv tau zoo los ntsuas qhov pom ntawm cov tshuaj qis-molecular-qhov hnyav, nyob rau hauv rooj plaub ntawmalbumin, nws tuaj yeem ua rau kev soj ntsuam yuam kev. Nrog xws li ib tug loj sib txawv nyob rau hauv lub concentration ntawm labeledalbuminNyob rau hauv lub plasma thiab lumen ntawm lub tubule, fluorescence teeb liab los ntawm lub filtrate tej zaum yuav muaj ntau zog los ntawm lub suab nrov tom qab. Tsis tas li ntawd, tus kws sau ntawv tau hais ntxiv tias qhov kev sib txuas ntawm tubule reabsorption system tej zaum yuav tsis muaj txiaj ntsig txaus los thauj ntau npaum li cas.albumin. Tsis tas li ntawd, de Borst [42] tau sau tseg tias cov txiaj ntsig tau nthuav tawm tsis tuaj yeem ua rau qhov kev txiav txim siab tsis meej thiab pom tias cov txiaj ntsig pom tau tuaj yeem tshwm sim los ntawm kev ua txhaum ncaj qha ntawm cov nyiaj ntau.albuminnyob rau hauv proximal tubular epithelial hlwb. Nws tau pom tias mus ntevalbuminraug txo qis endocytosis hauv proximal tubule cells [43]. Ntxiv mus, lwm cov kev tshawb fawb qhia tias siab heevalbumintheem induce apoptosis nyob rau hauv proximal tubule hlwb los ntawm kev txo megalin, protein kinase B, thiab phem protein [44]. Nyob rau hauv lem, nyob rau hauv cov lus tawm tswv yim ntawm Remuzzi li al. [45], cov kws sau ntawv suav nrog cov txiaj ntsig ntawm micro-puncture ntawm Munich-Wistar nas, uas zoo ib yam nrog GSC qhov tseem ceeb yav dhau los thiab uas tsis tau tshaj tawm ua ntej. Nyob rau hauv cov ntaub ntawv ntawm cov nas hais saum toj no, ib tug subset ntawm glomeruli nyob rau saum npoo ntawm lub raum, uas tso cai rau lub extraction ntawm ultrafiltrate ncaj qha los ntawm Bowman qhov chaw, yog li tsis suav nrog cov nyhuv ntawm reabsorption nyob rau hauv thawj seem ntawm lub tubule 46]. Muaj tseeb tiag, kev tshawb fawb ntxiv yog xav tau kom paub meej qhov tseeb GSC qhov tseem ceeb raualbuminlim.

cistanche txiv neej cov txiaj ntsig

3.2. Albumin Reabsorption muaj

Qhov chaw ntawmalbuminreabsorption tau paub zoo. Cov kev tshawb fawb uas tau ua tiav txij li thaum pib xyoo 1960, siv ntau yam kev siv tshuab microscopic, undoubtedly qhia tias cov txheej txheem no tshwm sim nyob rau hauv lub proximal tubule, ua tau zoo tshaj plaws nyob rau hauv nws thaum ntxov ntu [26]. Los ntawm kev siv hauv vivo micro-puncture, nws tau tsim qhov ntawdalbuminuptake yuav siv sij hawm qhov chaw nyob rau hauv ib tug zoo xws li cov nqi nyob rau hauv thaum ntxov thiab lig ib feem ntawm lub proximal convoluted tubule, thiab kuj yog ib feem nyob rau hauv lub nqis ib feem ntawm lub ncaj tubule. Tsis muaj qhov tseem ceebalbuminKev nqus tau pom nyob rau hauv lwm ntu ntawm nephron [27]. Txawm li cas los xij, lub mechanism ntawmalbuminuptake tseem unexplained rau lub sij hawm ntev. Lub proximal tubule yog lined nrog ib tug tuab cuboidal epithelium. Yog li, intracellular nkag mus ntawmalbuminlos ntawm cov epithelium mus rau hauv cov hlab ntsha zoo li tsis zoo li thaum pib. Nws kuj tseem yuav raug cuam tshuam los ntawm nws qhov loj me thiab tsis tshua muaj siab nyob hauv cov lim dej [46]. General kinetic yam ntxwv ntawm lubalbuminCov txheej txheem nqus dej tau muab los ntawm cov kev tshawb fawb pioneer ntawm Park thiab Mackin 1984 [47] siv cov perfused raum tubules cais. Lawv tau qhia tias muaj ob lub tshuab ua haujlwm: thawj tus, lub peev xwm siab-tsawg affinity system, tus cwj pwm los ntawm Michaelis tas li (Km) 1.2 mg / mL thiab (Bmax) 3.7ng / min ib hli tubule ntev, thiab qhov thib ob, muaj peev xwm tsis tshua muaj zog-siab affinity, nrog Km ntawm 0.031 mg/mL thiab khi muaj peev xwm Bmax ntawm 0.064 ng/min ib mm tubule ntev.

Kev tshawb fawb ntawm cov txheej txheem endocytosis nyob rau hauv cov kua dej theem (pinocytosis) nyob rau hauv proximal tubular epithelial hlwb tau pom tias nws txuas ntxiv nrog kev ua haujlwm tsawg dhau los piav qhia txog kev siv tau zoo ntawmalbumin. Kev nqus ntawm cov protein no tshwm sim yuav luag 40-fold sai dua nyob rau hauv cov ntaub ntawv ntawm cov tebchaw absorbed nyob rau hauv cov txheej txheem pinocytosis, xws li dextran los yog inulin [48].

Cov kev sim ua nyob rau hauv 1990s qhia tau hais tias uptake ntawmalbuminfeem ntau yog ib qho txheej txheem tshwj xeeb. Kev khi ntawm daim ntawv loalbumintuaj yeem yuav luag tag nrho inhibited los ntawm ntau tshaj ntawm unlabeled molecules. Tsis tas li ntawd, unlabeledalbuminTxhim kho qhov kev sib cais ntawm cov ntawv sau molecules los ntawm proximal tubular epithelial cell membrane. Lawv yog tus cwj pwm los ntawm kev sib cais tas li Ka nyob rau hauv thaj tsam ntawm 100-300·10-"M ({2}} mg/L). Cov albumin binding kinetics qhia tias muaj tsawg kawg yog ib qhov chaw sib khi. Cov yam ntxwv no qhia tias lub luag haujlwm tseem ceeb hauvalbuminreabsorption yog ua si los ntawm adsorptive endocytosis. Nws tau raug lees paub tias cov tshuaj inhibition ntawm cov txheej txheem no hauv nas los ntawm alkalization ntawm endosomes nrog NH Cl lossis bafilomycin A1 ua rau muaj kev nce ntxiv.albumintso zis hauv zis [43,49].

Tsis tas li ntawd, cov kev tshawb fawb ntawm proximal-tubule-derived opossum-kidney cells (OK cells) tau pom tiasalbuminendocytosis nyob ntawm cytoskeleton kev ncaj ncees. Inhibition ntawm actin polymerization los ntawm cytochalasin D ua rau yuav luag tiav kev ntes ntawmalbuminnqus. Thaj, cov txheej txheem kuj nrawm los ntawm kev cuam tshuam nrog microtubules. Ib qho cim txo qis hauv qhov nqus ntawmalbumintau pom los ntawm kev cuam tshuam ntawm microtubule vim qhov kev txiav txim ntawm nocodazole, tab sis qhov kev txiav tsis tiav. Nws zoo nkaus li tias kev txav ntawm vesicles los ntawm cov cell membrane mus rau endosomal compartment nyob rau hauv thawj theem ntawm endocytosis, nyob ntawm seb lub ncaj ncees ntawm lub cev pob txha, thiab kev sib cuam tshuam nrog microtubules tau pom nyob rau hauv lub tom ntej theem. Ntawm qhov tod tes, nws tau pom nyob rau hauv cov kev tshawb fawb no, tias clathrin-dependent endocytosis yog cov txheej txheem tseem ceeb ntawm molecules reabsorption [50,51]. Txawm hais tias caveolin qhia tau pom nyob rau hauv apical membrane ntawm proximal tubular epithelial hlwb, caveolin-dependent endocytosis yeej tsis tau tshaj tawm [52,53].

Tsuas yog cov kev tshawb fawb tsis ntev los no tau piav qhia txog cov txheej txheem molecular ntawmalbuminuptake nyob rau hauv proximal tubule mus rau ib tug zoo npaum li cas. Nws hloov tawm hais tias kev sib cuam tshuam ntawm cubilin nrog amnion tsawg protein (AMN) yog qhov tsim nyog rau kev noj qab haus huv ntawm cov protein no hauv cov tubule ze ze. Vim muaj kev sib raug zoo thiab kev ua haujlwm dependence ntawm lub complex, nws yog hu ua CUBAM. Tsis tas li ntawd, kev qhia kom raug thiab ua haujlwm tau zoo ntawm qhov kev ua haujlwm no yog nyob ntawm qhov thib ob endocytic receptor-megalin [54-56]. Ib txwm lub raum qhia thiab kev ua haujlwm ntawm CUBAM thiab megalin yog qhov tsim nyog rau kev siv tau zooalbuminnyob rau hauv proximal tubular hlwb, raws li tau pom los ntawm cov pov thawj ntawm albuminuria nyob rau hauv ntau yam kab mob los yog kis kab mob txog cov endocytic receptors (Table 1).

Tag nrho cov qauv thiab cov koom haum ua haujlwm ntawm cov receptor complex tau nthuav tawm hauv daim duab 1. Tsis ntev los no, nws tau pom nyob rau hauv cov kev tshawb fawb siv hepatocyte nuclear factor l knockout nas, tias cov protein no tswj cov lus qhia ntawm ob qho tib si receptors [63]. Megalin, cubilin thiab amnion tsis tshua muaj npe tam sim no thiab motifs. Megalin khi ntau yam lim cov proteins los ntawm nws hom kev rov ua dua thiab muaj peev xwm ua kom cov ligands ntawm NPXY motifs hauv cytoplasmic tus Tsov tus tw. Cubilin muaj ntau qhov sib txuas (CUB domains) thiab epidermal growth-factor-type (EGF-type) rov ua dua, raws li peripheral membrane protein uas nyob ntawm megalin thiab / lossis AMN.AMN muaj NPXY motif thiab tej zaum yuav pab cubilin hauv endocytosis ib yam nkaus. raws li nyob rau hauv intracellular thauj thaum lub sij hawm synthesis.

Table 1. Cov teeb meem cuam tshuam nrog lub raum tsis ua haujlwm ntawm albumin	Daim duab 1. Endocytic megalin-cubilin-ambitionless complex nyob rau hauv lub apical membrane ntawm lub raum proximal tubule.

NYEEM NO PART Ⅱ