Bioactive Food And Exercise in Chronic Kidney Disease

Bioactive zaub mov thiab kev tawm dag zog hauv cov kab mob raum tsis zoo: Targeting mitochondria

Denise Mafra^1,2ua al

Abstract

Mob raum mob(CKD), uas cuam tshuam rau 10 feem pua -15 feem pua ntawm cov pej xeem, muaj feem cuam tshuam nrog ntau yam teeb meem - xws li kab mob plawv, frailty, kab mob, nqaij, thiab pob txha mob, thiab kev laus ntxov ntxov - uas tuaj yeem cuam tshuam txog kev hloov pauv ntawm mitochondrial. naj npawb, faib, qauv, thiab muaj nuj nqi. Raws li mitochondrial biogenesis, bioenergetics thiab dynamic mitochondrial tes hauj lwm ncaj qha los yog indirectly tswj ntau intra- thiab extracellular functions, lub mitochondria tau tshwm sim raws li ib tug tseem ceeb lub hom phiaj rau kev pab cuam aiming ntawm kev tiv thaiv los yog txhim kho kev kho mob ntawm cov teeb meem nyob rau hauv CKD (Mob raum mob). Hauv qhov kev tshuaj xyuas no, peb tham txog lub luag haujlwm ntawm bioactive zaub mov tebchaw thiab kev tawm dag zog hauv kev hloov pauv ntawm kev cuam tshuam mitochondrial muaj nuj nqi hauv uraemic milieu.

KEYWORDS

mob raum mob, kev tawm dag zog, kev ua haujlwm mitochondrial, khoom noj khoom haus

Cistanche-kidney

Cistanche-lub raum

1|Taw qhia

Sib nrug los ntawm lawv qhov tseem ceeb hauv kev ua haujlwm metabolic (ATP ntau lawm thiab thermogenesis), mitochondria tau koom nrog hauv kev teeb tsa hauv lub cev, kev sib txuas ntawm cov biomolecules tseem ceeb, programmed cell tuag (apoptosis), thiab lwm yam txheej txheem ntawm tes. Rau lub hom phiaj no, mitochondria yog tswj los ntawm cov txheej txheem ntawm kev tswj hwm kev tswj hwm zoo uas ua kom zoo dua mitochondrial tooj (mitochondrial biogenesis; MB), kev faib tawm, thiab kev ua haujlwm. Cov txheej txheem tswj hwm no koom nrog cov synthesis ntawm cov proteins uas tau txais los ntawm lub nucleus thiab nruj me ntsis tswj los ntawm txoj hauv kev- thiab cov xov tooj ntawm tes.

Mitochondrial dysfunction yog txuam nrog nce oxidative kev nyuaj siab thiab metabolic ntshawv siab thiab tej zaum yuav los ntawm cov no thiab ntxiv mechanisms pab mus rau lub pathophysiology ntawm mob debilitating kab mob xws limob raum mob(CKD). Cov kev tshawb fawb tau pom cov mitochondria tshwj xeeb cuam tshuam ntawm bioactive compounds thiab kev tawm dag zog lub cev; Txawm li cas los xij, qhov muaj feem cuam tshuam ntawm cov kev cuam tshuam ntawm mitochondrial dysfunction hauv CKD txog tam sim no tau txais kev saib xyuas me ntsis. Hauv qhov kev tshuaj xyuas no, peb tham txog mitochondrial dysfunction nyob rau hauv cov ntsiab lus ntawm CKD thiab tam sim no muaj peev xwm kho cov tswv yim siv bioactive compounds thiab kev tawm dag zog los hloov kho mitochondrial muaj nuj nqi uas tuaj yeem txo cov teeb meem thiab txhim kho kev noj qab haus huv thiab lub neej zoo ntawm cov neeg mob CKD.

2|MITOCHONDRIA PHYSIOLOGY

Ob daim nyias nyias, sab nrauv thiab sab hauv, ntawm mitochondria, tsim ob qhov sib cais aqueous compartments, matrix, thiab qhov chaw nruab nrab. Lub puab mitochondrial membrane muaj cov enzyme complexes ntawm oxidative phosphorylation (OXPHOS) system. Cov txheej txheem metabolic koom nrog hauv cov piam thaj thiab fatty acids, xws li Krebs lub voj voog thiab oxidation, nyob rau hauv lub matrix ntawm mitochondria.6 Txawm hais tias mitochondria yog nyob rau hauv daim nyias nyias thiab txhais tau tias yog ib leeg organelles, lawv yuav tsum tsis txhob yuav. suav hais tias yog ib qho chaw, tab sis yog ib qho tangle ntawm dynamic thiab interconnected daim nyias nyias ua ib lub mitochondrial network. Fusions thiab fissions ntawm mitochondria yog cov xwm txheej tsis tu ncua uas ua rau muaj kev cuam tshuam ntawm cov mitochondrial network no. Dhau li ntawm cov nucleus, mitochondria yog tib lub organelles uas muaj cov khoom siv caj ces, mitochondrial DNA (mtDNA), uas yog ob-stranded ncig molecule ntawm kwv yees li 16.5 kb uas muaj 37 noob encoding rau 13 subunits ntawm OXPHOS complex, tshwj tsis yog complex II. Lub mtDNA kuj encodes 22 hloov RNAs thiab ob ribosomal RNAs. Txawm hais tias mitochondria tuav lawv tus kheej DNA, qhov me me ntawm mtDNA ua rau mitochondria muaj kev vam khom rau cov genome ntawm lawv lub xov tooj ntawm tes. Qhov tseeb, mitochondrial genomic machinery tsis unaided tswj lub organelle lub proteome raws li lub nuclear genome encodes feem coob ntawm tag nrho cov mitochondrial proteins (txog ~ 103) incorporated rau hauv mitochondria. Yav dhau los tsis paub cov yam ntxwv ntawm mitochondrial noob qhia, kev ua haujlwm, thiab kev tswj hwm qhia tau hais tias mitochondrial transcriptome thiab proteome yog qhov nyuaj dua li yav dhau los xav.

Treat Kidney disease--Cistanche acteoside

2.1|Mitochondrial biogenesis

Kev tsim ntawm mitochondria tshiab yog cuam tshuam los ntawm ib puag ncig kev ntxhov siab, xws li kev tawm dag zog, oxidative stress, hypoxia, cov tshuaj hormones, o, caloric txwv, thiab cell division/differentiation. Mitochondrial biogenesis cuam tshuam nrog kev sib koom ua ke thiab kev hloov pauv ntawm mtDNA thiab ntau yam nuclear-derived factor.2 Qee qhov tseem ceeb tshaj plaws hauv MB tau piav qhia hauv daim duab 1. Peroxisome proliferator-activated receptor (PPAR)-cactivator 1 (PGC-1) pab. raws li tus tswv regulator ntawm MB thiab yog teb rau physiological (xws li ce thiab caloric txwv) thiab pathologic (xws li oxidative kev nyuaj siab thiab o) tej yam kev mob. PGC-1 nyob rau hauv cytoplasm thiab translocates raws li phosphorylation-los ntawm AMP-activated protein kinase (AMPK), sirtuin-1 (SIRT-1), PPAR- thiab cAMP-responsive element-binding protein (CREB)-rau lub nucleus qhov twg Nws cuam tshuam nrog lwm yam kev hloov pauv, xws li nuclear respiratory factor (Nrf-1), Nrf-2 thiab transcription factor A mitochondrial (TFAM), yog li txhim kho lawv cov haujlwm. PGC-1, lwm qhov kev hloov pauv, qhia txog cov qauv molecular zoo sib xws thiab kev ua haujlwm nrog PGC-1, suav nrog kev sib txuas ntawm cov khoom siv hluav taws xob thiab kev hloov pauv hloov pauv, thiab tseem tswj hwm MB los ntawm kev sib koom cov txheej txheem nrog PGC-1, xws li ua kom Nrf-1.2 Lub tshuab ua pa nuclear. (Nrf-1 / Nrf-2) yog txuam nrog kev qhia ntawm ntau yam mitochondrial proteins, xws li OXPHOS complex proteins, enzymes ntawm haeme biosynthesis thiab cov proteins koom nrog hauv mitochondrial ntshuam ntawm nuclear-encoded sub[1]units. Nrf-1 transcription kuj yog tswj los ntawm PPAR- nyob rau hauv cov leeg nqaij ntawm cov nas ce, ib tug mechanism uas ua rau kom MB los ntawm upregulation ntawm AMP-activated protein kinase (AMPK) thiab Nrf-1 / Nrf-2 uas integrates lawv cov teebmeem ntawm cov noob ntawm nuclear. MB nrog kev txhawb nqa ntawm kev rov ua dua thiab hloov pauv ntawm TFAM. Cov tom kawg yog cov protein ntau uas muaj nyob rau hauv cov pab pawg neeg muaj zog (HMG) cov proteins uas yog cov yam ntxwv ntawm lawv lub peev xwm los khoov, qhwv thiab tso siab rau mtDNA yam tsis muaj qhov tshwj xeeb, tab sis nrog kev nyiam sib cuam tshuam nrog qee thaj tsam tau txheeb xyuas.

Cov qog suppressor protein p53 yog lub npe hu ua "tus saib xyuas ntawm mitochondria genome" thiab muaj peev xwm hloov kho qhov kev qhia ntawm ob qho tib si mitochondrial thiab nucleus noob. cell-cycle ntes, reactive oxygen hom (ROS) clearance, los yog apoptosis.

2.2|Bioenergetic

Cov dej num bioenergetic koom nrog cov txheej txheem ntawm OXPHOS uas tshwm sim nyob rau hauv lub cristae invaginations ntawm lub puab mitochondrial membrane, qhov twg txo nicotinamide adenine dinucleotide (NADH) thiab FADH2 pro[1] ua nyob rau hauv lub mitochondrial matrix los ntawm lub Krebs voj voog thauj electrons mus rau electron. complexes I-V. Cov twj tso kua mis proton (complexes I, III thiab IV) tso cov protons rau hauv qhov chaw nruab nrab rau kev sib txuas ntawm adenosine 5′-triphosphate (ATP), lub zog tseem ceeb ntawm lub cell, ntawm phosphorylation ntawm ADP los ntawm ATP. synthase. Cov Cheebtsam no ua haujlwm ua ke nrog cov protein tsis sib txuas (UCPs) uas ua rau cov cua sov ua kom sov rau thermogenesis. Thaum lub sij hawm hloov ntawm electrons, qee qhov ua pa nyuaj ua pa tawm electrons rau oxygen, ua rau superoxide anion (O2 •). Raws li qhov tshwm sim, mitochondria yog lub hauv paus loj ntawm ROS ntau lawm, txheej txheem inevitable; Txawm li cas los xij, thaum muaj kev tsis ua haujlwm ntawm bioenergetics, oxidative kev nyuaj siab nce.

Mitochondrial tes hauj lwm yog heev dynamic thiab teb rau cellular perturbations. Tsis tu ncua mitochondrial fusion thiab fission txheej txheem tswj mitochondrial architecture. Mitofusin 1 (Mfn1), mitofusin 2 (Mfn2) thiab optic atrophy 1 (Opa1) proteins yog lub luag haujlwm rau mitochondrial fusion, thiab mitochondrial fission factor (Mff) thiab dynamin-related protein 1 (Drp1) yog lub luag haujlwm rau mitochondrial fission. Cov kev hloov hauv mitochondrial architecture yog txuam nrog mitochondrial dysfunction, uas nyob rau hauv lem yog txuam nrog ntau yam kab mob, xws li CKD, thiab pab mus rau ntau yam pathological txheej txheem nyob rau hauv cov neeg mob CKD.

Cistanche-kidney

Cistanche-lub raum

3|MITOCHONDRIAL DYSFUNCTION IN KIDNEY DISEASE

Mitochondrial dysfunction yog ib qho tseem ceeb ntawm ob qho tib si CKD thiab mobmob raum(AKI)37 thiab muaj feem xyuam nrog ntau cov txheej txheem suav nrog biogenesis, bioenergetics, morphology, thiab degradation. Tsis tas li ntawd, CKD yog txuam nrog kev txo qis hauv Nrf-1, PGC1- kev qhia nrog rau TFAM spell tawm, cytochrome C oxidase subunit 6C (COX6C) thiab cytochrome C oxidase subunit 7C (COX7C) thiab mitochondrial respiratory system.

Hauv CKD, mitochondrial dysfunction yog ib qho tseem ceeb rau oxidative kev nyuaj siab uas cuam tshuam nrog ntau yam teeb meem uraemic, nrog rau kev mob thiab vascular puas tsuaj uas txhawb cov kab mob plawv thiab kev laus ntxov ntxov.40 Tsis tas li ntawd, muaj qhov txo qis hauv mtDNA tus lej, biomarker tseem ceeb rau mitochondrial. rupture nyob rau hauv lub raum kab mob, poob ntawm mitochondrial membrane muaj peev xwm thiab txo ATP ntau lawm nyob rau hauv CKD, thiab o thiab oxidative kev nyuaj siab, nyob rau hauv lem, tshwm sim los txhawb mitochondrial tsis ua hauj lwm. Thaum lub sij hawm oxidant insults, ob peb mito [1] chondrial functions raug cuam tshuam nrog ntxiv permeability ntawm mitochondrial hloov pores uas ua rau membrane muaj peev xwm depolarization, inhibition ntawm electron thauj, nce oxidant ntau lawm thiab ua tsis taus pa ua pa, txo intracellular ATP theem, alterations nyob rau hauv mitochondrial membrane muaj peev xwm. (Δψm) thiab ua rau kev tso tawm ntawm cytochrome C (Cyt C) mus rau cytoplasm uas tuaj yeem ua rau ua kom cov caspases, ua rau kev tuag ntawm tes.

Lwm qhov kev xav yog tias mitochondria dysfunction hauv CKD cuam tshuam rau hemodynamic adaptations, vim yog qhov kev xav tau ntawm cov pa oxygen tsis sib haum nrog qhov ua rau hypoxia thiab ua kom muaj kev cuam tshuam ntawm hypoxia-inducible factor 1 (HIF-1). Qhov no txo qis mitochondrial oxygen noj thiab superoxide ntau lawm thiab nce mitochondrial ntim ceev. Ntxiv mus, uraemic toxin indoxyl sulfate tsim los ntawm plab microbiota txo qhov kev qhia ntawm PGC-1 thiab nce autophagy hauv cov leeg pob txha. Thaum kawg, txij li qhov tsis txaus ntawm cov zaub mov tseem ceeb tuaj yeem ua kom cov mitochondrial lwj, hlau deficiency yog ib qho kev txhawj xeeb tseem ceeb hauv CKD.

Ua ke,mob, nce ROS ntau lawm, uraemic toxin, thiab hypoxia tuaj yeem nyob ib leeg lossis hauv kev hais kwv txhiaj ua lub luag haujlwm hauv uraemic mitochondrial dysfunction. Txawm hais tias cov txheej txheem hauv qab no tseem tsis paub ntau, nws xav tias yuav koom nrog hauv cov txheej txheem kev laus thiab cov kab mob ntawm ntau cov kab mob. Yog li, mitochondrial tsis ua haujlwm tuaj yeem ua lub luag haujlwm tseem ceeb hauv cov kab mob ntawm CKD. Nephrons yog nplua nuj nyob rau hauv mitochondria, thiab OXPHOS ntawm fatty acids - oxidation yog lub ntsiab ntawm ATP ntau lawm. Qhov kev raug mob thawj zaug tuaj yeem ua rau muaj kev hloov pauv mitochondria metabolism cuam tshuam nrog redox imbalance ua rau muaj kev hloov pauv hauv bioenergetics thiab CKD kev loj hlob. Txij li cov txheej txheem ntawmraumKev puas tsuaj los ntawm mitochondrial dysfunction tseem tseem tsis tau paub, kev tshawb fawb ntxiv ntawm mitochondrial biology thiab pathophysiology tau lees paub rau kev tshawb pom ntawm cov kev kho mob zoo hauv cov kab mob raum. Hauv qab no, peb nthuav qhia cov pov thawj tias kev tawm dag zog thiab cov tshuaj bioactive muaj peev xwm hloov kho mito[1] chondrial muaj nuj nqi hauv CKD.

4|NUTRITIONAL STRATEGIES TARGETING MITOCHONDRIAL DYSFUNCTION IN CKD

Raws li kev ua haujlwm tsis zoo mitochondria pab txhawb ROS ntau lawm, lawv yuav yog lub hom phiaj tsim nyog rau bioactive compounds nrog antioxidant zog. Tseeb tiag, kev noj haus antioxidants, xws li vitamin C, polyunsaturated fatty acids (PUFA), quercetin, resveratrol, thiab curcumin, yuav txo tau mitochondrial oxidative puas. Txawm hais tias nws ntseeg tau tias cov as-ham no tuaj yeem txhim kho mitochondrial muaj nuj nqi hauv CKD, tsuas yog qee qhov kev sim kev tshawb fawb tau ua dhau los. Hauv kev tshuaj xyuas no, peb tau tshawb nrhiav cov ntaub ntawv ntawm kev kho cov txheej txheem siv bioactive compounds los txhim kho mitochondrial muaj nuj nqi thiab lawv lub luag haujlwm hauv kev tiv thaiv cov teeb meem uraemic, saib daim duab 2.

Resveratrol,ib tug natural polyphenolic compound pom nyob rau hauv txiv hmab txiv ntoo, berries, thiab liab cawu cub, tau pom tias muaj kev koom tes nyob rau hauv MB los ntawm ib tug sirtuin-1-dependent mechanism thiab nce complex I kev ua. Lagouge et al (2006) tau qhia tias C57BI / 6J nas kho nrog resveratrol tau nthuav tawm kev ua haujlwm ntawm PGC-1 los ntawm SIRT1-mediated deacetylation thiab cov lus qhia Nrf-1 thiab TFAM kuj tau qhib. Hauv tsib ntawm rau nephrectomized nas, resveratrol txhim kho mitochondrial zog raws li qhia los ntawm kev nce hauv ATP cov ntsiab lus thiab nce kev nthuav qhia ntawm mitochondrial electron thauj saw proteins, thiab txo ROS theem thiab complex I thiab complex III kev ua ub no. Txawm hais tias cov neeg ua haujlwm uas cuam tshuam rau mitochondrial biogenesis thiab NAD kev hloov pauv, xws li resveratrol, tuav cov lus cog tseg hauv kev kho cov teeb meem hauv CKD, lawv cov kev kho mob txhais lus tseem tos kev tshawb nrhiav ntxiv.

Quercetin, ib qho senolytic compound60 pom nyob rau hauv nplooj ntsuab, capers, dos, txiv apples, berries, txiv lws suav, thiab zaub paj, tau pom tias ua kom PGC-1, mtDNA thiab cyt C replication.61 Txawm hais tias quercetin tuaj yeem muaj txiaj ntsig cardioprotective los ntawm kev nce PGC-1 qhia. thiab cov cim cim cuam tshuam nrog lub peev xwm bioenergetic, qhov cuam tshuam ntawm cov flavonoid no tsis tau sim hauv cov neeg mob CKD. Interestingly, tab sis, quercetin attenuated vascular calcification los ntawm kev txo oxidative kev nyuaj siab thiab tiv thaiv mitochondrial fission txheej xwm nyob rau hauv ib tug adenine-nplua nuj noj zaub mov-induced CKD nas qauv thiab nyob rau hauv vitro nyob rau hauv lub cev nqaij daim tawv nqaij hlwb.62 Txij li thaum vascular calcifications yog ib tug ntau yam feature ntawm uraemic phenotype thiab kwv yees. Kev tuag ntawm cov hlab plawv, quercetin tuaj yeem yog ib qho

nthuav cov ntsiab lus los kawm ntxiv hauv CKD.

Curcuminyog ib qho polyphenol pom nyob rau hauv rhizome ntawm Curcuma longa, feem ntau siv los ua txuj lom. Hauv cov qauv tsiaj ntawm kev sim CKD, curcumin tiv thaiv mitochondrial dysfunction thiab txo qis oxygen noj los ntawm kev txo ROS ntau lawm. Txawm li cas los xij, nws tau raug tshaj tawm tias curcumin yog qhov nyuaj rau kev kawm vim nws tau degraded sai hauv vivo thiab muaj bioavailability tsawg heev. Curcumin, nrog rau lwm yam polyphenols, activates Nrf-2 thiab txhawb kev tiv thaiv antioxidant. Txawm hais tias kev paub txog qhov tseeb molecular kev ua ntawm cov polyphenol no tsuas yog txwv, nws tau raug tshawb fawb kom meej txog kev mob qog noj ntshav. Txawm li cas los xij, hauv kev sim nas qauv ntawm CKD, nws tsis ntev los no tau pom tias curcumin tuaj yeem muaj txiaj ntsig zoo los ntawm kev txo qis qhov mob thiab oxidative kev nyuaj siab los ntawm kev tswj hwm ntawm Nrf-2. Yog tias qhov no muaj tseeb kuj tseem nyob hauv CKD tseem yuav raug tsim.

Anthocyanidinsyog polyphenols pom nyob rau hauv blueberries, liab thiab dub grapes, cranberries, raspberries, blackberries, liab cabbage, liab dos, thiab eggplants. Cov txheej txheem ntawm kev txiav txim ntawm anthocyanins muaj feem xyuam rau lub peev xwm redox uas tso cai rau nws los ua ib qho khoom siv hluav taws xob ntawm txoj kev I ntawm mitochondrial electron thauj system thiab cyt C. Txawm hais tias anthocyanins zoo li yog electron txais hauv complex I-mediated oxidation ntawm NADH thiab muab cardioprotection, 70 cov teebmeem ntawm cov polyphenol no tsis tau sim hauv cov ntsiab lus ntawm CKD. Txawm li cas los xij, siv tus qauv adenine-induced CKD hauv cov nas nyuam qhuav pom tias kev tswj hwm ntawm anthocyanins txo qis cov teebmeem ntawm adenine-induced CKD. Lub hauv paus txheej txheem ntawm cov txiaj ntsig zoo ntawm anthocyanins hauv cov qauv nas no tau pom tias yog los ntawm kev ua tus antagonist rau oxidative kev nyuaj siab thiab los ntawm kev txo qis qhov mob. Yog li ntawd, Anthocyanins tuaj yeem yog tus neeg sawv cev noj zaub mov zoo los txiav txim siab hauv kev kho CKD.

Epigallocatechin-3-gallate (EGCG)yog ib qho polyphenolic compound muaj nyob rau hauv cov tshuaj yej ntsuab (Camellia sinensis Theaceae) uas yuav hloov kho mitochondrial muaj nuj nqi thiab tswj bioenergetics. Txawm li cas los xij, qhov cuam tshuam tiag tiag ntawm catechin EGCGs, piv txwv li rau qhov twg nws ua rau MB, tseem tsis tau paub ntau, tab sis kev tshawb fawb tau tshaj tawm tias nws ua rau muaj zog antioxidant thiab ROS scavenger. Txawm hais tias muaj pov thawj ntau txhawb kev ua haujlwm ntawm EGCGs ua cov tshuaj tiv thaiv kab mob hauv vitro, cov pov thawj rau cov teebmeem hauv vivo tseem tsis muaj.Omega -3, polyunsaturated fatty acids (PUFA, nplua nuj nyob rau hauv ntses roj, tam sim no anti-thrombotic, antiatherogenic, thiab anti-inflammatory functions. Cov fatty acids no yog PPAR ligands thiab nce PGC-1, TFAM, thiab cyt C oxidase qhia, membrane muaj peev xwm, thiab ATP. Taneda li al qhia tias nas tubular epithelial hlwb kho nyob rau hauv vitro thiab nyob rau hauv vivo nrog eicosapentaenoic acid (EPA) qhia txo mitochondrial apoptosis los ntawm kev tiv thaiv cyt C tso rau cytosol thiab yuav txo tau caspase-9 activation, ib tug marker ntawm mitochondrial apoptosis. Laila et al tau kawm txog cov teebmeem ntawm koob tshuaj siab (3.9 g / hnub) n3-PUFA rau 4 lub hlis ntawm mitochondria los ntawm vastuslateralis nqaij biopsies rau cov neeg laus. Kev txo qis hauv ROS ntau lawm. Tsuas yog qee qhov kev tshawb fawb me me tau tshawb xyuas qhov muaj txiaj ntsig zoo ntawm PUFA hauv CKD. Cov nyhuv ntawm cov tshuaj omega-3 ntawm ob qho tib si omega-6 thiab omega-9, piv rau cov placebo supplementation, tau pom muaj kev txhim kho tseem ceeb ntawm pruritus hauv CKD.

Coumestrolyog ib qho polyphenol nrog cov khoom estrogen pom muaj nyob rau hauv raw clover sprouts, liab clover, alfalfa, soybeans, legumes, Brussel sprouts, thiab spinach. Cov tshuaj bioactive no tuaj yeem ua rau muaj kev cuam tshuam los ntawm kev mob qog noj ntshav los ntawm kev cuam tshuam rau kev muaj peev xwm thiab kev ua haujlwm mitochondrial thiab provoking apoptosis los ntawm inhibition ntawm PI3K / AKT thiab ua kom MAPKs (ERK1 / 2 thiab JNK). Interestingly, coumestrol tau pom tias yuav qhib SIRT-1 thiab yog li pib MB hauv kab lis kev cai nas pob txha hlwb. Siv tib neeg placental choriocarcinoma hlwb, nws tsis ntev los no tau pom tias coumestrol induces apoptotic teebmeem ntawm cov hlwb los ntawm kev tswj cov xov tooj ntawm tes thiab mitochondrial-mediated functions mas los ntawm stimulating ROS ntau lawm. Txawm li cas los xij, kev tshawb fawb hauv cov neeg mob CKD tseem tsis muaj.

Vitamin C(ascorbic acid) yog ib qho dej-soluble vitamin nyob rau hauv ntau cov txiv hmab txiv ntoo thiab zaub xws li guava, liab qab zib kua txob, kiwi, txiv qaub, txiv kab ntxwv, thiab txiv kab ntxwv qaub. Cov qauv hauv vitro qhia tau hais tias vitamin C modulates mitochondrial zog los ntawm kev txo Ca^{2 plus}overload thiab ROS tiam, thiab los ntawm kev ua kom lub mitochondrial ATP-sensitive poov tshuaj raws (mitoKATP raws); Qhov no ua rau muaj kev ruaj khov mitochondrial membrane muaj peev xwm. Txawm li cas los xij, rau qhov zoo tshaj plaws ntawm peb txoj kev paub, tsis muaj kev tshawb fawb tseem tsis tau kuaj seb puas muaj vitamin C supplementation augments mitochondrial function.

Muab ua ke, txij li cov khoom noj khoom haus bioactive no tuaj yeem cuam tshuam rau MB, kev tshawb nrhiav ntxiv hauv kev sim tshuaj ntsuam xyuas tau lees paub los tshawb txog lawv lub peev xwm rau kev tiv thaiv thiab kev kho mob ntawm uraemic phenotype.

5|CEEB TOOM THIAB MITOCHONDRIAL FUNCTION hauv CKD

Qib qis ntawm lub cev ua si thiab cov leeg pob txha pob txha txo qis hauv cov neeg mob CKD yog txuam nrog sarcopenia thiab muaj kev pheej hmoo siab ntawm kev tuag ntxov ntxov. Ntau qhov kev tshawb fawb tau pom qhov tseem ceeb ntawm kev ua lub cev tsis tu ncua los tiv thaiv cov leeg nqaij, ua kom muaj peev xwm ua kom muaj zog thiab txhim kho lub neej zoo hauv cov neeg mob CKD. Tsis tas li ntawd, kev tawm dag zog ua kom rov ua haujlwm mitochondrial thiab txhawb nqa lub pas dej mitochondrial noj qab haus huv uas txhawb nqa cov leeg nqaij.

Qhov tseeb, cov leeg nqaij mitochondrial metabolic hloov pauv tuaj yeem tshwm sim hauv cov neeg mob CKD nrog kev khaws cia lub cev ua haujlwm thiab lub zog sib txuas (piv txwv li, mitochondrial efficiency), qhia tias kev hloov pauv mitochondrial metabolism hauv CKD yuav yog qhov tseem ceeb dua li qhov sib txawv ntawm kev ua haujlwm ntawm lub cev. Tseem, lwm cov kev tshawb fawb qhia tau hais tias kev hloov pauv hauv kev ua haujlwm mitochondrial thiab biogenesis, nrog rau cov leeg nqaij pob txha, tuaj yeem rov qab los nrog kev tawm dag zog hauv CKD txawm hais tias qhov tseeb mechanism tsis meej. Txawm li cas los xij, ntau qhov kev tshawb fawb qhia tau hais tias kev khaws cia ntawm cov pob txha pob txha thiab kev ua haujlwm hauv CKD tuaj yeem tshwm sim tsis hais hom kev tawm dag zog, ob peb txoj kev tshawb fawb tau tshawb xyuas mitochondrial muaj nuj nqi hauv kev teb rau kev tawm dag zog hauv CKD (tib neeg lossis tsiaj).

Hauv kev tshawb fawb tsiaj, cov nas uas muaj lub raum tsis ua haujlwm koom nrog kev tawm dag zog (ua luam dej lossis lub log khiav) tuav cov haujlwm citrate synthase (siv raws li kev ntsuas tsis ncaj ntawm mitochondrial ntom ntom) thaum kis kab mob thiab qhov no tshwm sim los tiv thaiv qhov kev xav tau ntawm cov leeg pob txha. Yog li, kev tswj cov leeg pob txha noj qab haus huv txhawb kev noj qab haus huv feem ntau. Cov kab lus no tsis ntev los no tau txhawb nqa los ntawm kev tshawb nrhiav kev tshawb fawbmob raumnyob rau hauv tus qauv nas overexpressing PGC-1 nyob rau hauv ib mus[1]cle-specific yam. Cov kws sau ntawv nthuav tawm cov pov thawj rau lub raum tiv thaiv lub luag haujlwm ntawm myokine irisin thiab qhia tias cov leeg-mob raum crosstalk tuaj yeem cuam tshuam.raumfibrosis thiab metabolic reprogramming thaum lub sij hawmmob raum.

Nyob rau hauv sib piv rau txoj kev tshawb no los ntawm Kiuchi et al nyob rau hauv cov neeg mob CKD, ib tug tsis ntev los no txoj kev tshawb fawb soj ntsuam cov teebmeem ntawm 8 lub lis piam ntawm high-siv sij hawm kev cob qhia (HIIT) (85 feem pua VO2max) nyob rau hauv ib tug murine qauv ntawm thaum ntxov-theem CKD tsis ntev los no qhia tau hais tias txo qis. oxidation- thiab mob-mediated puas nyob rau hauv lubraum.Qhov zoo siab, HIIT tau ua pov thawj zoo dua rau ob qho kev tawm dag zog qis (45 feem pua - 50 feem pua VO2max) thiab tus cwj pwm sedentary hauv kev tawm tsam.raum puas.Cov txiaj ntsig zoo no tau pom tias yog nyob ntawm qhov kev nthuav qhia siab ntawm cov noob ntsig txog endogenous antioxidant enzyme kev ua haujlwm thiab mob. Txawm li cas los xij, rau peb txoj kev paub, tsis muaj HIIT concurrent los yog ua ke kev cuam tshuam kev kawm hauv CKD cov neeg mob tau tshuaj xyuas mitochondrial muaj nuj nqi lossis cov cim ntawm mitochondrial oxidative muaj peev xwm hauv cov leeg pob txha lossis lwm cov ntaub so ntswg.

Txawm hais tias kev tshawb fawb soj ntsuam ntawm kev tawm dag zog lub cev ntawm kev ua haujlwm ntawm mitochondria hauv cov neeg mob CKD tsis tshua muaj, hauv qab no peb tham txog qee qhov kev tshawb fawb hauv cov neeg mob no. Balakrishnan thiab al tau pom tias cov neeg mob uas muaj mob hnyav-rau- mob CKD, randomized mus rau 12 lub lis piam ntawm kev kawm tiv thaiv lossis tswj kev ua si, tau nthuav tawm ntau dua mtDNA tus lej tom qab kev tawm dag zog. Kev tawm dag zog aerobic, xws li kev cob qhia lub voj voog nyob rau lub sijhawm 6 lub hlis, tuaj yeem txhim kho vascularization ntawm cov leeg nqaij gastrocnemius, nce VO2max thiab txhim khu kev tawm dag zog, thiab hauv ib txoj kev tshawb fawb, CKD cov neeg mob tau txhim kho lawv cov VO2 ncov los ntawm 50 feem pua -70 feem pua. Txawm li cas los xij, seb mitochondrial ntom ntom yog txuas ncaj qha rau kev ua pa ntawm lub plawv ntsuas raws li VO2 ncov / max tau raug nug txawm hais tias nce MB thiab qhov ceev ntawm mitochondria yog qhov paub zoo txog kev hloov mus rau kev ua kom muaj zog. Ib txoj kev tshawb fawb tsis ntev los no hauv cov neeg mob uas muaj qhov nruab nrab-rau- mob hnyav CKD tau tshawb xyuas cov txiaj ntsig ntawm kev txwv caloric, kev tawm dag zog aerobic (alternating treadmill, elliptical cross-trainer, Nu-Step cross-trainer, thiab recumbent stationary bicycle), los yog kev sib koom ua ke ntawm kev cuam tshuam thaum lub sijhawm 4-lub hlis. Txhua pab pawg tau pom tias txo qis oxidative kev nyuaj siab txawm hais tias kev sib koom ua ke (kev noj haus ntxiv rau kev tawm dag zog) ua pov thawj zoo tshaj plaws. Cov kev tshawb pom no qhia tias cov kev cuam tshuam zoo li no tuaj yeem txo qis kev ua haujlwm mitochondrial.

Kev sib xyaw ua haujlwm thiab kev cob qhia aerobic, kev cob qhia ib ntus, thiab kev siv lub sijhawm ntev (HIIT) tau txais txiaj ntsig ntau xyoo dhau los thiab tau txuas nrog kev txhim kho hauv kev ua haujlwm mitochondrial thiab biogenesis. Txawm hais tias kev cuam tshuam ib puag ncig / HIIT kev kawm kev kawm hauv cov neeg mob CKD raug txwv, kev tshawb fawb tsis ntev los no tau hais tias kev cob qhia ua ke muaj txiaj ntsig zoo hauv cov neeg mob nondialysis CKD piv rau cov kev qhia aerobic. Cov txiaj ntsig zoo no tau tshwm sim los ua kev txhim kho ntau dua hauv cov leeg nqaij thiab kev ua siab ntev, yam tseem ceeb rau kev txhim kho thiab tswj hauv cov neeg mob CKD. Qhov zoo siab, CKD cov neeg mob ntshav siab tau ua raws li lub sijhawm 3 xyoos los ntawm kev tshuaj xyuas lub plawv los ntsuas qhov cuam tshuam ntawm HIIT lossis kev tawm dag zog nruab nrab thiab muaj peev xwm cuam tshuam rau atrial fibrillation thiab lub raum ua haujlwm. Ntawm qhov kev ceeb toom, txoj kev tshawb fawb qhia tau hais tias cov neeg mob CKD koom nrog HIIT muaj peev xwm muaj qhov tshwm sim ntau dua ntawm atrial fibrillation piv rau cov neeg mob koom nrog kev tawm dag zog nruab nrab. Ntxiv mus, saib ntawm lub raum ua haujlwm, kev tawm dag zog me ntsis kuj zoo li muaj txiaj ntsig zoo rau cov neeg mob no dua li HIIT.

6|NYEEM NTXIV

Mitochondrial dysfunction zoo li yog ib qho tshwm sim thiab tej zaum qhov kev hloov pauv ntawm CKD uas tuaj yeem txhawb txoj kev loj hlob ntawm cov kab mob hauv qab thiab ua rau muaj teeb meem ntawm CKD, xws li oxidative stress thiab o. Txawm hais tias cov txheej txheem tsis meej, mitochondrial dysfunction hauv CKD tuaj yeem yog qhov tshwm sim ntawm kev ua haujlwm tsis zoo ntawm mitochondrial biogenesis, cuam tshuam hauv bioenergetics, dynamics, turnover, thiab caj ces hloov. Tag nrho cov kev hloov pauv no tuaj yeem ua rau muaj kev puas tsuaj mitochondrial, tsub zuj zuj ntawm mtDNA tsis ruaj khov, thiab kev cuam tshuam hauv lub cev xws li nce oxidative kev nyuaj siab thiab apoptosis. Hauvraum, kev cuam tshuam hauv mitochondrial homeostasis tuaj yeem ua rau cov microvasculature puas, txhawb kev mob thiab fibrosis, thiab pab txhawb kev loj hlob ntawm CKD. Hauv cov neeg mob uas muaj CKD siab heev, mitochondrial dysfunction yuav ua rau sarcopenia, o, thiab nce oxidative kev nyuaj siab, cov xwm txheej uas cuam tshuam nrog cov txiaj ntsig tsis zoo. Kev hloov pauv khoom noj khoom haus thiab kev tawm dag zog ib leeg lossis nyiam dua hauv kev sib xyaw ua ke zoo li muaj txiaj ntsig zoo hauv kev tsom mus rau mitochondria hauv CKD. Txawm hais tias nws tsis muaj kev ntseeg siab tias lub cev ua si, tejzaum nws los ntawm kev cawm mitochondrial functions, muab cov txiaj ntsig zoo rau cov leeg nqaij pob txha thiab kev ua haujlwm thiab tseem txhim kho lwm yam ntawm cov neeg mob kev noj qab haus huv, cov ntaub ntawv los ntawm bioactive as-ham ntawm mitochondrial muaj nuj nqi tseem tsawg. Raws li kev paub tam sim no, kev tawm dag zog yuav tsum tau txhawb nqa thoob plaws txhua theem ntawm CKD. Txawm li cas los xij, cov kev tshawb fawb ntxiv tau lees paub kom paub seb qhov txiaj ntsig zoo ntawm kev tawm dag zog hauv CKD tau txuas rau mitochondria thiab seb cov khoom noj khoom haus bioactive puas muaj txiaj ntsig zoo rau mitochondria.

Cistanche khoom raumob raum mob

TXOJ CAI

Peb ua tsaug rau Conselho Nacional de Desenvolvimento Cientí- fico e Tecnológico (CNPq) thiab Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) rau lawv txoj kev txhawb nqa thiab Lub Plawv thiab lub ntsws Foundation thiab Njurfonden rau kev txhawb nqa kev tshawb fawb ntawm Peter Stenvinkel. Njurfonden kuj txhawb Ferdinand von Walden. Baxter Novum yog qhov tshwm sim ntawm Baxter Healthcare rau Karolinska Institutet. Bengt Lindholm ua haujlwm los ntawm Baxter Healthcare.