Tshooj 2: Lub luag haujlwm ntawm vitamin K hauv Kab Mob Raum Hniav: Kev tsom mus rau pob txha thiab mob plawv

Yog xav paub ntxiv. tiv taujtina.xiang@wecistanche.com

4. Vitamin K thiab mob raum mob

Mob raum mob(CKD) cov neeg mob muaj tus cwj pwm tsis zoo ntawm cov vitamin K [28]. Ntau yam tuaj yeem cuam tshuam rau cov khw muag vitamin K hauv cov neeg mob CKD, thiab cov laj thawj tseem ceeb ntawm nws qhov tsis txaus muaj xws li kev txwv tsis pub noj zaub mov, uremia-sociated dysbiosis, thiab tshuaj [29-31]. Ntxiv mus, kev txwv tsis pub noj zaub mov vim muaj cov ntsiab lus ntawm cov poov tshuaj hauv feem ntau cov vitamin K-nplua nuj zaub ntsuab pab txhawb rau nws qhov tsis txaus [12]. Nrog rau kev noj zaub mov noj, vitamin K rov ua dua los ntawm "vitamin K voj voog", uas suav nrog vitamin K epoxide reductase, DT-diaphorase, thiab g-glutamyl carboxylase. Kev txo qis ntawm cov vitamin K tau pom hauv nas nrog CKD, yuav tshwm sim los ntawm kev txo qis ntawm g-glutamyl-carboxylase, nrog cov txheej txheem zoo ib yam li coumarins.

Cov neeg mob cuam tshuam los ntawm CKD paub tias muaj kev pheej hmoo ntau ntxiv ntawm kev txhim kho vascular calcification (VC) thiab pob txha pob txha [34], uas ua rau muaj kev mob siab dua thiab kev tuag ntawm cov neeg mob CKD [34,35]. Ntau cov ntawv tshaj tawm qhia tias vitamin K2 tuaj yeem ua lub luag haujlwm tseem ceeb hauv kev tsim cov kab mob thiab tiv thaiv cov teeb meem loj.

Ib txoj kev tshawb nrhiav kev soj ntsuam hla ntu, VIKI (Vitamin K Italian) txoj kev tshawb fawb, tau soj ntsuam kev sib koom ua ke ntawm cov vitamin K reserves, vertebral fractures, thiab vascular calcifications, qhia txog qhov feem ntau ntawm cov vitamin K deficiency nyob rau hauv qhov chaw ntawm 387 hemodialysis cov neeg mob. VK1 qhov tsis txaus ua rau muaj qhov muaj zog tshaj plaws ntawm cov pob txha pob txha (qhov sib txawv [OR], 2.94; 95 feem pua ​​​​ntawm kev ntseeg siab [CI], 1.38-6.26), thaum qhov tsis txaus ntawm MK-4 yog ib qho tus kwv yees rau aortic calcification (OR, 2.82; 95 feem pua ​​CI, 1.14-7.01).

Kev kho mob hemodialysis, sevelamer (phosphate binder), los yog vitamin K Antagonists (VKA) sawv cev rau qhov loj iatrogenic ua rau vitamin K deficiency hauv cov neeg mob.mob raum tsis ua haujlwm[39]. Cov neeg mob CKD, suav nrog cov kev kho mob hemodialysis, feem ntau siv cov tshuaj VKA, tshwj xeeb tshaj yog rau cov mob stroke prophylaxis hauv atrial fibrillation (AF). Warfarin, yog li, tuaj yeem ua rau cov pob txha tawg thiab vascular calcification los ntawm cov txheej txheem sib txawv: ncaj qha, los ntawm inhibiting carboxylation ntawm osteocalcin (pob txha Gla protein los yog BGP) thiab lwm cov pob txha matrix proteins, thiab indirectly, vim hais tias ntawm kev noj zaub mov kom tsawg ntawm cov khoom noj uas nplua nuj nyob rau hauv. vitamin Kin warfarin-cov neeg siv [40]. Tam sim no, cov non-vitamin K qhov ncauj anticoagulants (NOACs) tau siv ntau los tiv thaiv mob stroke thiab cardioembolic teeb meem hauv AF cov neeg mob es tsis txhob siv cov vitamin K antagonists. Txawm li cas los xij, lawv siv nyob rau hauv cov qib siab CKD thiab cov kab mob hauv lub raum kawg (ESRD) yog rau hnub contraindicated [41].

Tseeb, Siontis et al. pom kev los ntshav tsawg dua nrog cov qauv koob tshuaj (5 mg × 2 / hnub) ntawm apixaban dua li cov vitamin K inhibitor nrog rau kev txo qis ntawm kev pheej hmoo ntawm thromboembolism hauv kev tshawb fawb rov qab nrog rau cov neeg mob ESRD nrog AF [42].

Vitamin K2 txo bioavailability vim phosphate binders (PBS) tej zaum yuav txawv raws li cov binder thiab hom menaquinone [39, 43-45]. Neradova et al. txheeb xyuas qhov ua tau los ntawm kev sib txuas ntawm PBs sib txawv ntawm vitamin K2 (MK-7) [44]. Calcium acetate / magnesium carbonate khi vitamin K2 txawm hais tias muaj phosphorus, lanthanum carbonate tsuas yog thaum tsis muaj phosphorus, hos sucroferric oxyhydroxide thiab sevelamer carbonate tsis khi vitamin K2 hauv vitro [44]. Interestingly, kev tshawb nrhiav tsis ntev los no siv tus qauv nas los ntawm Neradova li al., pom tias kev sib xyaw ntawm cov vitamin K2 noj zaub mov thiab kev kho PBs txo qis VC, piv rau MK7 lossis PBs kev kho mob ib leeg [40]. Txawm li cas los xij, kev siv sevelamer tau cuam tshuam nrog MK-4 tsis txaus, nrog rau kev tswj hwm warfarin [39]. Cov laj thawj tshuaj tseem tsis tau raug tshawb xyuas, xav tias cov no yog cov ntawv cog lus feem ntau vim yog daim ntawv chelate [44]. Ntawm qhov tod tes, kev sib koom ua ke ntawm calcium mimetics thiab vitamin D analogs nrog cov vitamin K supplementation tau pom tias muaj txiaj ntsig zoo dua piv rau kev tswj hwm ntawm txhua cov vitamins ntawm tus kheej, nrog rau kev siv tshwj xeeb rau pob txha noj qab haus huv [46]. Cov kev txiav txim siab zoo sib xws tuaj yeem siv rau qhov nyuaj ntawm kev hloov lub raum (KT) cov neeg mob [6]. Qhov tseeb, kev mob plawv tsis zoo uas cuam tshuam txog vascular calcifications tuaj yeem txuas rau qhov tsis tshua muaj vitamin K hauv cov neeg tau txais KT. Ib qho kev koom tes ntawm thoracic aorta calcification thiab lub sij hawm luv luv ntawm kev kho mob mvcophenolate mofetil (MMF), ib qho tshuaj tiv thaiv kab mob, nrog rau kev siv cov tshuaj tiv thaiv vitamin-K yav dhau los, tau lees tias qis dua dp-ucMGP qib hauv KT cov neeg mob tau txais kev kho MMF. Qhov tshwm sim no yeej tseem tuaj yeem tshwm sim los ntawm kev txhim kho cov khoom noj khoom haus thiab kev txhawb nqa ntau dua ntawm micronutrient [47].

Nyem qhov no kom paub txog kev siv cistanche

4.1.Vitamin K: Lub luag haujlwm muaj peev xwm hauv kev txhim kho thiab kev loj hlob ntawm CKD

Qes peripheral vitamin K raws li txoj cai tau yav tas los txuam nrog proteinuria thiab CKD theem [48]. Cov decarboxylated matrix protein Gla (DP-ucMGP) tau siv los ua tus cim tsis ncaj ncees rau kev txiav txim siab ntawm cov vitamin K ntau ntawm 3969 tus neeg uas muaj hnub nyoog nruab nrab ntawm 52.3 ± 11.6 xyoo (48 feem pua ​​​​txiv neej), rau npe hauv "Kev Tiv Thaiv Kab Mob Rau Lub Raum thiab Vascular End-stage Disease [49,50]. Cov txiaj ntsig ntawm kev tshawb fawb no tau sawv cev los ntawm kev kuaj mob ntawm CKD (kwv yees Glomerular Filtration Rate (eGFR)<60 ml/min/1.73="" m')or="" the="" occurrence="" of="" microalbuminuria.="" during="" the="" 7.1="" years="" of="" follow-up,205(5.4%)="" participants="" developed="" ckd,="" and="" 303="" (8.4%)="" developed="" microalbuminuria.="" for="" each="" doubling="" of="" plasma="" decarboxylated="" matrix="" protein="" gla,="" the="" risk="" of="" the="" onset="" of="" ckd="" and="" microalbuminuria="" was="" 1.85="" [95%="" confidence="" interval(ci)1.59-2.16,=""><0.001] and="" 1.19(95%="" ci1.07-1.32;p="0.001)," suggesting="" a="" possible="" prognostic="" value="" of="" dp-ucmgp="" in="" ckd,="" as="" it="" could="" imply="" a="" role="" for="" poor="" vitamin="" k="" status="" in="" the="" development="" of="">mob raum tsis ua haujlwm[51]. Hauv kev tshuaj xyuas tsis ntev los no, nws twb tau sau tseg tias ob qho tib si tsis muaj vitamin K thiab 25 OH-vitamin D, nyob rau hauv yuav luag sib npaug ntsuas, tau cuam tshuam nrog kev nce qib ntawm cov vitamin K.lub raum ua haujlwmpoob qis thiab nrog nce albumin / creatinine urinary excretion ratio [48]. Ntxiv mus, cov vitamins D thiab K tau raug pom zoo los koom tes hauv kev ua kom muaj txiaj ntsig zoo ntawm kev tiv thaiv pob txha, qeeb VCprogression, thiab hauv kev txhim kho cov hlab plawv[52]. Ntawm qhov tod tes, Kurnatowska li al., kuj tseem hais txog qhov siab dua ntawm dp-ucMGP. Hauv cov neeg mob CKD, tshwj xeeb tshaj yog nyob rau theem V. Kev tswj hwm ntawm vitamin K2 (90 mcg / hnub) ua rau txo qis hauv qib dp-ucMGP. Txaus siab heev,

plasma dp-ucMGP concentrations yog inversely correlated nrog eGFR thiab ncaj qha correlated nrog proteinuria thiab serum creatinine [53]. Yuav ua li cas vitamin K tuaj yeem ua rau nephroprotective, kuj tseem txo qis proteinuria, tseem tsis tau nkag siab thiab xav tau cov pov thawj ntxiv.

4.2.CKD-MBD

Mob raum kab mob-mineral pob txha tsis meej (CKD-MBD) yog ib lo lus siv los txheeb xyuas qhov kev puas tsuaj ntawm cov pob txha zoo thiab qhov tshwm sim ntawm kev loj hlob ntawm cov pob txha thiab cov ntxhia hauv cov metabolism hauv lub raum ua haujlwm tsis zoo [54]. Qhov no ua rau tsis muaj kev cuam tshuam rau cov neeg mob CKD, tshwj xeeb tshaj yog cov neeg mob hemodialysis, muaj kev pheej hmoo siab dua ntawm pob txha, piv rau cov pej xeem.

Kev kho pob txha yog cov txheej txheem txuas ntxiv ua haujlwm tau ua los ntawm ob qho tib si antagonistically acting hlwb, osteoblasts, uas tswj cov pob txha tsim, thiab osteoclasts, lub luag hauj lwm rau cov pob txha resorption txheej txheem.

Ntau qhov kev tshawb fawb (ob leeg hauv vivo thiab hauv vitro) tau ua pov thawj tias vitamin K ncaj qha koom nrog hauv cov pob txha metabolism. Qee qhov ntawm no tau pom tias vitamin K2 inhibits pob txha resorption tej zaum, ib feem vim yog txo qis ntawm cov pob txha resorbing tshuaj xws li prostaglandin E2 thiab interleukin 6. Nws kuj tau pom tias vitamin K muaj peev xwm txhawb tib neeg osteoblast-induced pob txha mineralization hauv vitro thiab inhibit pob txha poob hauv steroid-kho lossis ovariectomized nas[58]. Vitamin K2 kuj yog cofactor rau qee cov proteins koom nrog hauv pob txha mineralization, uas yog osteocalcin (pob txha Gla protein lossis BGP) thiab matrix Gla protein (MGP).

BGP yog ib qho protein me me ntawm 5.6 kDa, muaj 49 amino acids, uas yog tsim nyob rau hauv cov pob txha los ntawm osteoblasts thiab tsawg tsawg secreted rau hauv txoj kev. Raws li matrix Gla protein, nws muaj nyob rau hauv carboxylated thiab decarboxylated cov ntaub ntawv [60]; Lawv cov qib ntshav tau cuam tshuam los ntawm hnub nyoog thiab cov tshuaj hormonal. Ob daim ntawv nce nrog lub hnub nyoog, tab sis tom qab menopause decarboxylated osteocalcin predominates. Nws yog feem ntau koom nrog hauv kev tsim cov hydroxyapatite thiab kev sib sau ntawm cov pob txha pob txha tab sis tau pom tias muaj ntau yam kev ua haujlwm ntxiv ntawm cov piam thaj thiab lub zog metabolism, kev tsim tawm, thiab kev txawj ntse [62].Qhov tseeb, nws kuj txhawb kev tso tawm ntawm insulin los ntawm kev ua haujlwm. ncaj qha rau ntawm lub txiav thiab tsis ncaj qha inducing lub secretion ntawm glucagon-zoo li peptide 1 GLP-1) thiab adiponectin nyob rau hauv cov hnyuv me, koom nrog hauv cov metabolism hauv qabzib. Interestingly, BGP kuj tau pom tias yuav txhawb nqa angiogenesis thiab upregulate nitric oxide (NO) qhia nyob rau hauv endothelial hlwb, qhia txog lub luag hauj lwm tiv thaiv ntawm cov protein no hauv kev txo cov kev pheej hmoo ntawmkab mob plawv.

MGP yog 10.6 kDa protein, muaj 84 amino acids, insoluble hauv dej. Nws yog tsim los ntawm cov leeg nqaij leeg thiab chondrocytes thiab muab zais rau hauv cov matrix extracellular. Nws inhibits calcification thiab tsuas yog qhib tom qab cov txheej txheem ntawm carboxylation thiab phosphorylation. Vitamin K, raws li ib tug cofactor, pab txhawb nws carboxylation ntawm 5 glutamic acid residues ntawm txoj hauj lwm 2,37,41,48, thiab 52 los ntawm Y-glutamyl carboxylase; Tsis tas li ntawd, 3 serine residues yog phosphorylated ntawm txoj hauj lwm 3,6, thiab 9 los ntawm casein kinase. Cov txheej txheem ntawm inhibiting vascular calcification yuav tshwm sim los ntawm kev khi ntawm calcium ions los ntawm pawg carboxyl [66,67].

GLA-nplua nuj protein ntau (GRP) muaj qhov hnyav molecular ntawm 10.2 kDa thiab muaj 74 amino acids. Zoo li lwm yam matrix proteins, GRP yog vitamin K nyob ntawm thiab inhibits vascular calcifications, ua zoo ib yam li cov matrix Gla protein, los ntawm kev khi thiab sequestrating calcium ions.

Loj hlob Arrest Specific Protein 6 (GAS6) yog 75 kDa protein, qhib rau hauv cov txheej txheem vitamin K-dependent carboxylation. GAS6 feem ntau yog koom nrog hauv kev tswj hwm kev loj hlob ntawm tes thiab kev loj hlob thiab yog zais los ntawm osteoblasts rau cov pob txha matrix [69]. Hauv kev nthuav dav, tsis zoo li lwm yam VKDPs, GAS6 tau pom tias yuav ua rau muaj kev ua haujlwm osteoclast yog li txhawb cov pob txha resorption.

Hauv CKD, pib los ntawm theem IIIA, qhov kev puas tsuaj ntawm cov pob txha tuaj yeem tshwm sim nrog cov pob txha loj lossis qis, ua rau muaj kev pheej hmoo siab dua ntawm pob txha [71]. Cov duab sib txawv tuaj yeem piav qhia txog qhov sib txawv ntawm cov tshuaj parathyroid hormone (PTH) thiab cov pob txha hloov pauv: hyperparathyroid osteopathy, lossis siab tig-osteopathy; Qhov no yog tus cwj pwm los ntawm theem nrab hyperparathyroidism, osteomalacia thiab osteoporosis, thiab adynamic pob txha kab mob (ABD), nrog rau tom kawg muaj cov qib PTH qis thiab txo cov pob txha rov qab, cov pob txha tsawg tab sis nrog cov ntxhia hauv ib txwm, thiab txo qis cellularity nrog tsawg lossis tsis muaj fibrosis. 72] ib. Ntxiv rau PTH, vitamin D, calcium, thiab phosphorus, fibroblast kev loj hlob zoo tshaj -23(FGF-23), sclerostin, thiab Klotho ua lub luag haujlwm hauv CKD-MBD (Daim duab 1) [71,73] .

Cov pob txha sclerostin ntau ntxiv kuj tseem tuaj yeem ua lub luag haujlwm hauv kev txhim kho FGF-23 qhia, raws li nws tau ua pov thawj los tswj FGF-23 [74,75]. Tsis tas li ntawd, Polignano li al., yav dhau los qhia tau tias Cathepsin-K, lysosomal cysteine ​​protease secreted los ntawm activated osteoclasts thiab txhawb cov pob txha thiab extracellular matrix remodeling, yog txuam nrog PTH theem, nyob rau hauv ib qho chaw ntawm 85 mob hemodialysis cov neeg mob, qhia tias cov protein no tuaj yeem ua rau cov neeg mob hemodialysis. sawv cev rau biomarker ntawm CKD-MBD qhov hnyav thiab PTH qib [76-80].

Vitamin K2 zoo nkaus li koom nrog hauv qhov kev sib cuam tshuam molecular no [24,81,82]. Hauv kev tshawb fawb tau ua rau 210 tus poj niam uas muaj pob txha, tom qab rau lub hlis ntawm kev kho mob nrog vitamin K2, tag nrho cov kev ntsuas ntawm cov metabolism thiab pob txha ceev tau nce ntxiv, qhia txog kev ua haujlwm osteogenic. Lwm cov kev tshawb fawb tau lees paub cov pov thawj no [83]. Tsis tas li ntawd, vitamin K2 tiv thaiv kev ua haujlwm osteoclastic. Rangel et al. pom tau tias muaj kev nce hauv pob txha loj hauv cov nas ovariectomized ntxiv nrog cov vitamin K[84]. Nyob rau tib lub hauv paus, 374 tus poj niam postmenopausal nrog osteoporosis muaj pob txha ntau dua nrog cov pob txha tsis muaj zog yog tias lawv nthuav tawm nrog vitamin K tsis txaus [85]. Hauv kev ua haujlwm yav tom ntej ntawm 241 cov neeg mob osteoporotic ntawm ob leeg poj niam txiv neej, kev tswj hwm ntawm 45 mg / hnub ntawm vitamin K2 ua rau muaj kev txo qis hauv pob txha [86]. Ib qho lus nug tseem ceeb kuj tau hais txog qhov ua tau zoo ntawm cov vitamin K2-25OH vitamin D3 ua ke. Matsunaga et al. tau pom tias kev kho mob ua ke zoo li muaj txiaj ntsig zoo dua li kev tswj hwm ib leeg hauv kev tiv thaiv cov pob txha poob ntawm femoral ncej thiab hauv tibial metaphysis hauv ovariectomized nas [87]. Kev tshawb fawb ntawm cov neeg hemodialysis tam sim no tseem tsawg tab sis tag nrho cov pov thawj qhia tias vitamin K tsis muaj peev xwm yog ib qho kev kwv yees ntawm kev pheej hmoo ntawm pob txha [88-90].

4.3.Vitamin Kand Hypertension hauv CKD

Cov neeg mob CKD uas tau txais tag nrho cov vitamin K tsis txaus (ob qho tib si Kl thiab K2) muaj cov hlab plawv thiab tag nrho cov ua rau tuag ntau dua li cov uas tau txais txaus [91]. Vitamin K tsis muaj peev xwm tau lees paub tias yog ib qho kev kwv yees ntawm tus kab mob plawv (CVD) pheej hmoo [92]. Ntxiv mus, vitamin K2 tsis txaus los yog vitamin K functional inhibition los ntawm warfarin thawj coj ua rau calcium deposition nyob rau hauv cov hlab ntsha arterial [13]. Tsis tas li ntawd, vitamin K2 tau pom tias ua rau me ntsis nce HDL cholesterol thiab txo qis hauv lub cevmob[93, 94]. Raws li qhov tshwm sim, nws cov tshuaj ntxiv tuaj yeem ua rau qeeb vascular puas tsuaj thiab tiv thaiv atherosclerosis, CVD, thiab mob stroke [95-9]. Tseeb tiag, kev sib txuas ntawm kev kwv yees ntau dua menaquinone tau txais (ntau dua 21.6 ug / hnub) thiab txo qis cov kab mob plawv ntsig txog kev tuag thiab aortic calcification tau pom, tab sis tsis muaj qhov sib cuam tshuam rau phylloquinone [99-101]. Nyob rau hauv txoj kev tshawb fawb PREVENT, kev ua haujlwm tsis txaus vitamin K tau kuaj pom hauv 31 feem pua ​​​​ntawm tag nrho cov neeg kawm, thiab qhov tshwm sim muaj ntau dua ntawm cov neeg laus thiab cov neeg uas muaj kev sib txawv, xws li kub siab, ntshav qab zib hom 2, CKD, thiab kab mob plawv [102] . Cov txiaj ntsig ntxiv los ntawm cov kev sim tshuaj ntsuam xyuas tsis tu ncua yuav ua kom pom tseeb zoo dua yog tias thiab ntawm qhov ntau npaum li cas vitamin K1 lossis K2 ua rau qeeb ntawm VC hauv cov neeg mob CKD[103-106]. Cov txheej txheem thoob ntiaj teb pom zoo rau kev saib xyuas cov ntshav ntshav siab qis dua 130/80 mmHg kom txo qis kev pheej hmoo ntawm lub raum hauv cov neeg mob no [107]. Vitamin K2 zoo li muaj lub luag haujlwm txhawb nqa hauv kev kho mob ntshav siab thawj zaug [108,109]. Liu Tian-Hao et al kuj tau tshawb xyuas lub hauv paus txheej txheem los ntawm kev mus rau 16S rRNA sequencing, qhia txog kev cuam tshuam ntawm vitamin K2 ntawm lub zog ntxiv, calcium signals, thiab renin-angiotensin-aldosterone system (RAAS) hauv kev sim qauv ntawm ntsev- rhiab heev arterial hypertension. RAAS kev koom tes hauv cov qauv ntawm cov ntsev-vim cov hlab ntsha ntshav siab tau muaj kev lees paub thiab kev tswj hwm ntawm cov vitamin K2 tau pom tias muaj kev cuam tshuam inhibitory ntawm RAAS-txhim kho txoj hauv kev. Hauv tib txoj haujlwm, kev tshuaj xyuas ntxiv tau coj mus rau kev txheeb xyuas cov kab mob, suav nrog Dubosiella thiab Ileibacterium, nyiam ua rau RAAS hloov kho. Qhov kev tshawb pom no kuj tau coj mus rau qhov kev xav tias cov tshuaj probiotics raws li cov kab mob no tuaj yeem pab txhim kho cov metabolism thiab tiv thaiv kab mob los ntawm kev nce synthesis ntawm vitamin K2 rau kev saib xyuas cov haujlwm endothelial.

Txhawm rau txhawb qhov kev tshawb fawb no, Jensen li al., tau tshaj tawm cov ntaub ntawv ntawm 79 cov neeg mob ntshav siab hauv Oakland qhia tias kev noj cov txiv ntoo nattokinase-fermented soybean, nplua nuj nyob rau hauv vitamin K2, cuam tshuam nrog kev hloov pauv hauv cov ntshav siab (txawm hais tias cov ntshav siab diastolic tsuas yog ua tiav qhov tseem ceeb, thaum lub systolic txo qis tus qauv tau pom zoo) [113]. Ntxiv mus, ib rooj plaub ntawm hypotension tau tshaj tawm tom qab kev tswj hwm ntawm menaquinone [114]. Mansour et al., kuj tau qhia tias yuav ua li cas, siv MK-7, txhais tau tias arterial siab (MAP) thiab peripheral diastolic ntshav siab (DBP) txo [115]. Txawm li cas los xij, kev hloov ntshav siab ntawm Vitamin K supplementation tau sib cav, thiab cov ntaub ntawv tsis zoo ib yam rau hnub tim. Qhov tseeb, kev soj ntsuam tsis tau lees paub qhov kev txo cov ntshav siab no [116-121]. Tseeb tiag, kev sib txuas ntawm pathophysiological ntawm vitamin K xwm txheej thiab kev tswj ntshav siab tsis tau pom meej meej txog tam sim no.

Muaj ntau qhov kev xav txog phylloquinone (VK1). Phylloquinone, nrog rau cov vitamin K2, plays lub luag haujlwm tseem ceeb hauv cov kab mob plawv. Phylloquinone deficiency tau pom tias yog qhov muaj feem cuam tshuam rau qhov xwm txheej CVD hauv cov laus kho mob ntshav siab. Txawm li cas los xij, kev noj cov vitamin K1 tsis zoo li cuam tshuam nrog kev pheej hmoo ntawm CVD. Qhov no tuaj yeem yog vim kev ua ub no, feem ntau mob siab, ntawm vitamin K1, thaum vitamin K2 exerts extrahepatic sawv daws yuav. Txawm li cas los xij, vitamin K1 kuj zoo li koom nrog hauv cov kev ua ub no ntxiv, thiab nws tau pom zoo los ua lub luag haujlwm hauv kev ncua cov hlab ntsha thaum noj ntau dua 2 mg / tuag, nrog rau txo qis vascular calcification [122-124], Txawm hais tias Bellinge li al., tsis tau lees paub qhov txo qis ntawm cov hlab ntsha calcification los ntawm kev tswj hwm vitamin K1 [125]. Txawm li cas los xij, kev noj cov vitamin K1 tam sim no tsis txaus siab vim nws cov ntaub ntawv tsis zoo los ntawm cov ntaub ntawv. Tsis tas li ntawd, cov txiaj ntsig vitamin K2 zoo li muaj zog dua li cov vitamin K1, kuj yog vim nws qhov ntev ib nrab ntawm lub neej thiab ntau dua nyob rau hauv cov ntaub so ntswg extrahepatic ntawm tag nrho cov K2 vitamers [28].

Tam sim no tsis muaj pov thawj txog qhov muaj txiaj ntsig ntawm vitamin K3 supplementation hauv CKD, arterial hypertension, thiab CVD. Tsis tas li ntawd, koob tshuaj vitamin K3 tau raug nug kom muaj peev xwm ua rau muaj tshuaj lom (xws li, daim siab puas, hemolytic anemia, thiab lwm yam) [18], thiab nws cov kev tswj hwm hauv tib neeg tsis pom zoo thoob ntiaj teb. Txawm li cas los xij, vitamin K3 yog yooj yim thiab pheej yig tsim, thiab nws yog ruaj khov heev vim tsis degraded los ntawm lub teeb, thiab tsawg-kuaj yuav siv tau los kho vitamin K deficiency [18,126,127]. Los ntawm txoj kev, tseem tsis muaj kev tshawb fawb txaus txog nws cov supplementation hauv cov neeg mob no.

Ntshav siab yog ib qho ntawm thawj qhov ua rau AF [128,129].Nyob rau hauv pawg neeg mob no, qhov kev pheej hmoo ntawm VC thiab CVD hloov pauv kuj muaj feem xyuam rau cov tshuaj anticoagulant (VKAs vs. NOAC. Ntau qhov kev sim tshuaj tau qhia tias VKAs txhawb atherosclerotic calcification [ 97].Nyob rau hauv cov ntsiab lus no, peb yuav tsum kom meej meej saib ntawm qhov kev pheej hmoo / txiaj ntsig piv.

Cov kev xav no tseem muaj ntau dua tam sim no hauv cov neeg mob CKD. Tseeb, nyob rau hauv cov neeg no, muaj kev pheej hmoo ntxiv rau kev sib koom ua ke ntawm kev kub siab, CKD, thiab siv tau VKA (Table 1).

5. Kev sib tham

Hauv cov neeg mob CKD, qhov sib npaug tshwm sim ntawm cov pob txha metabolism tsis zoo thiab CVD tau pom ntau; cov tom kawg yog feem ntau txhawb los ntawm VC, uas nyob rau hauv lem yog txiav txim los ntawm ntxhia dysregulation [130]. Hauv kev nthuav dav, phosphate retention tshwm sim hauv CKD pom zoo nrog kev hloov pauv ntawm vascular du leeg hlwb mus rau osteoblast zoo li cov hlwb tsim cov pob txha matrix proteins uas tswj cov phab ntsa ntawm phab ntsa calcification [131]. Accumulating evi-dence qhia tias qhov complex "calcification paradox" tuaj yeem kho tau los ntawm vitamin K. Yog li, kev ntsuam xyuas ntawm vitamin K concentration tau raug pov thawj tias muaj peev xwm tseem ceeb hauv cov neeg mob CKD, nrog rau lub luag haujlwm tseem ceeb ntawm cov as-ham no. Cov cim rau qhov xwm txheej CVD, CKD kev loj hlob thiab kev loj hlob, thiab qhov tshwm sim CKD-MBD.In no lub teeb, vitamin K supplementation yuav tsum raug pom zoo [52]. Txij li thaum vitamin K2 muaj ib nrab-lub neej ntev (hnub) dua li cov vitamin K1 (teev), nws tuaj yeem kwv yees tias kev ntxiv nrog vitamin K2, uas yog qhov tseem ceeb rau cov kab mob siab VKDPs, tej zaum yuav pheej yig dua [132]. Txawm li cas los xij, kev siv cov vitamin K1 tuaj yeem ua tau zoo vim nws muaj peev xwm hloov mus rau hauv vitamin K2 tab sis nyob rau hauv koob tshuaj 10 npaug siab dua vitamin K2, yog li daim teb no tseem nyob hauv kev sib cav [124]. Vitamin K toxicity tsis tau lees paub, thiab lub siab ntev ntawm cov vitamin K tsis tau tsim kom deb li deb [100], raws li tau tshaj tawm hauv cov lus pom zoo dhau los [133]. Txawm hais tias nws tau raug nug tias nws muaj peev xwm ua rau muaj kev phom sij ntau dhau los ntawm cov teeb meem coagulation ntau dhau, kev noj tshuaj ntau heev tau pom tias muaj kev cuam tshuam nrog hypoprothrombinemia hauv cov ntaub ntawv tsis tshua muaj neeg [93,134]. Qhov tseeb, qhov kev pom zoo txog cov koob tshuaj niaj hnub xav tau los tiv thaiv kev ua ntej ntawm VC lossis qhov tshwm sim ntawm pob txha hauv CKD cov pej xeem tsis tau mus txog. Txawm li cas los xij, 10 mg rau vitamin K1 thiab 360 mcg / tuag mus txog rau ntau dua 1080 mcg / tuag rau MK-7 tau raug npaj ua ib qho tshuaj txaus[6]. Yog li, vitamin K supplementation (tshwj xeeb yog menaquinone-vitamin K2) tuaj yeem muaj lub luag haujlwm tiv thaiv ob qho tib si ntawm cov pob txha thiab cov hlab plawv hauv cov neeg mob CKD. Qhov tseeb, kev sib koom ua ke tau pom zoo ntawm cov vitamins D thiab Kin ua rau cov pob txha tiv thaiv, nrog rau kev ua kom qeeb ntawm VC thiab txhim kho cov hlab plawv [52]. Txawm li cas los xij, tsis muaj RCTs tau tsim los txog tam sim no txhawm rau tshawb nrhiav kev sib xyaw ua ke hauv cov neeg mob CKD. Vitamin K vitamer lub luag haujlwm muaj peev xwm cuam tshuam rau daim siab, lub raum, lub caj pas parathyroid, pob txha, cov hlab ntsha, thiab lub plawv tau piav qhia hauv daim duab 2.

Raws li Kev Tshawb Fawb Kev Tshawb Fawb tau muab los ntawm European Food Safety Authority (EFSA), cov vitamin K noj zaub mov muaj txiaj ntsig (DRVs) rau cov neeg nyob sab Europe tau kwv yees li 1 ug / kg lub cev qhov hnyav hauv ib hnub ntawm phylloquinone, uas sib haum rau tus nqi ntawm 70 ug phylloquinone / hnub rau cov neeg laus, ob leeg poj niam, thiab txiv neej. Txij li cov ntaub ntawv hais txog kev nqus ntawm menaquinones, kev ua haujlwm, thiab cov ntsiab lus hauv lub cev lossis lub cev tsis muaj zog, EFSA tau tso tawm cov lus pom zoo kom noj txaus rau phylloquinone nkaus xwb [100]. Qhov nyiaj ntawm phylloquinone tuaj yeem ua lub luag haujlwm hauv kev txo qis ntawm CVD kev loj hlob, tshwj xeeb tshaj yog nyob rau hauv Arterial Hypertension ua rau arterial calcification kev ua si thiab arterial stiffening [122,124,125]. Tseem tsis muaj kev tshawb fawb txog nws lub luag haujlwm hauv kev tiv thaiv CVD.

Lub National Institutes of Health (NIH) muab nws cov lus pom zoo rau kev noj thiab kev tswj hwm ntawm Vitamin K vitamers, los ntawm Lub Chaw Haujlwm Saib Xyuas Kev Noj Qab Haus Huv [135]. Txawm li cas los xij, tam sim no tsis muaj kev pom zoo meej txog yuav ua li cas ntxiv cov vitamin K, txawm tias nrog zaub mov lossis tshuaj ntxiv. Ob peb cov ntaub ntawv hais txog bioavailability ntawm ntau hom vitamin K los ntawm cov khoom noj muaj nyob. Cov kab mob sib xyaw ua ke txhawb nqa me me rau kev tsim cov menaquinones, tab sis nws qhov kev txhawb nqa tseeb tseem tsis meej [16]. Ntau cov vitamins thiab / lossis cov khoom noj muaj txiaj ntsig tam sim no muaj vitamin K, ib leeg lossis ua ke nrog lwm cov as-ham (calcium, magnesium, vitamin D), feem ntau muaj cov ntsiab lus ntawm vitamin K tsawg dua 75 feem pua ​​​​ntawm cov nqi txhua hnub [17,135]. Ntxiv randomized placebo-tswj kev sim siv phylloquinone, menaquinones, lossis kev sib xyaw ntawm cov vitamers sib txawv yog xav tau kom paub meej tias kev tswj hwm cov vitamin K zoo tuaj yeem tiv thaiv kev puas tsuaj thiab vascular calcifications hauv CKD.

6. Cov lus xaus

Qhov kev tshuaj xyuas no muab kev nkag siab txog qhov tshwm sim ntawm kev ua haujlwm ntawm vitamin K tsis txaus thiab nws qhov cuam tshuam rau kev kho mob hauv CKD, tshwj xeeb yog tsom rau cov pob txha thiab CV kev noj qab haus huv, nrog rau kev mob ntshav siab thiab ua rau lub raum puas. Raws li peb txoj kev paub, cov txiaj ntsig ntawm vitamin K supplementation ntawm arterial hypertension kuj nyob rau hauv cov pej xeem hemodialysis yeej tsis tau sib cav ntau. Kev tshawb fawb tsis tu ncua

qhia txog vitamin K raws li txoj kev kho tshiab, txawm hais tias kev siv tshuaj kho mob kom tau txais cov txiaj ntsig ntawm kev ntxiv cov khoom noj no tseem tsis tau raug txiav txim siab thiab cov pov thawj ntxiv yog qhov xav tau. Yog li ntawd, raws li qhov tshwm sim los ntawm peb cov ncauj lus ntxaws ntxaws ntawm cov ntaub ntawv thiab cov kev sib txawv ntawm cov pej xeem CKD, yuav tsum tau npaj lub tswv yim rau tus neeg mob.