Pro-Inflammatory Profile ntawm Adipokines nyob rau hauv Obesity Pab rau Pathogenesis, Khoom noj khoom haus tsis zoo, thiab mob plawv txaus ntshai nyob rau hauv mob raum Ⅱ

4. Kev sib deev Dimorphism hauv Obesity-Induced Metabolic Profile

Lub hauv paus faib ntawm AT ib txwm ntawm cov txiv neej muaj feem cuam tshuam nrog qhov tshwm sim ntau duametabolic ntshawv siabtshaj qhov gluteal-femoral faib ntawm AT. Tsis tas li ntawd, pear-type silhouette yog txuam nrog atxo kev pheej hmoo ntawm cov kab mob metabolicthiab tej zaum yuav muaj ibtiv thaiv qhov tshwm sim ntawm kev rog rogob lub qhov muag [26] Cov tshuaj estrogens, uas dominate nyob rau hauv cov poj niam, nce lubqib ntawm leptin thiab lwm yam anorexic compoundsxws li cholecystokinin, hlwb-derived neurotrophic factor (BDNF), thiab apolipoprotein A-IV, thiab ib txhij txo orexigenic tshuaj, xws li ghrelin thiab melanin-concentrating hormone. Kev tiv thaiv ntawm cov tshuaj estrogen tiv thaiv kev rog tsis yog tsuas yog txo qis kev noj zaub mov xwb tab sis kuj siv zog ntxiv [27]. Poj niam txiv neej tsis tsuas yog cuam tshuam rau kev faib khoom thiab hom AT tab sis kuj cuam tshuam rau hom kev ua haujlwm metabolic ntawm AT. Estrogens txo qhov mob hauv AT thiab ua rau nws ntau dua insulin-rhiab heev. Cov tshuaj estrogen txo cov haujlwm ntawm HIF-, uas yog lub luag haujlwm rau fibrosis thiab mob, los ntawm kev txhawb nqa kev hloov pauv ntawm enzyme prolyl hydroxylase domain enzyme 3 (PHD3) [27].

Nyob rau hauv lem, testosterone inhibits cov kev ua ntawm lipoprotein lipase, uas txo cov uptake ntawm fatty acids nyob rau hauv lub plab cov ntaub so ntswg. Kev cuam tshuam ntau dhau rau cov roj fatty acids dawb (FFAs) hauv cov hlab ntsha ua rau cov ntshav qabzib ntau ntxiv thiab ua rau cov tshuaj insulin ntau ntxiv. Nws ua rau txo qis ntawm cov ntaub so ntswg rhiab heev rau insulin. Qhov tshwm sim no yog ib qho laj thawj vim li cas txiv neej muaj kev cuam tshuam rau insulin tsis kam thiab metabolic syndrome [26]. Kev tso nyiaj ntau dua ntawm VAT hauv cov txiv neej, thiab yog li muaj kev pheej hmoo siab ntawm cov ntshav siab thiab CVD, tej zaum yuav yog vim muaj qib testosterone ntau dua hauv cov txiv neej dua li cov poj niam. Tsis tas li ntawd, nyob rau hauv cov poj niam postmenopausal, txo qis ntawm cov tshuaj estrogen kuj ua rau nce VAT thiab ntshav siab [28] .AT concentrated nyob ib ncig ntawm lub raum hu ua perirenal adipose cov ntaub so ntswg (PRAT) thiab yog ib feem ntawm visceral dawb adipose ntaub so ntswg. Lub morphology ntawm PRAT yog poj niam txiv neej-dependent. Hauv cov txiv neej, PRAT muaj qhov ntim ntau dua thiab tuab dua li cov poj niam nrog tib lub duav ncig. Tsis tas li ntawd, hauv cov poj niam, qhov kev qhia ntawm UCP1 hauv PRAT yog siab dua hauv cov txiv neej [29].

NEW HERBAL FORMULATION RAU QHOV TSEEB NTAWM METABOLIC DISEASE

Hauv cov qauv murine, nws tau pom tias muaj Y chromosome inhibits qhov kev qhia ntawm UCP1 hauv BAT. Txawm li cas los xij, Chen et al. qhia tias nws tsis yog qhov muaj Y chromosome uas ua rau muaj kev sib txawv ntawm poj niam txiv neej hauv AT, tab sis qhov nce ntawm X chromosomes. Cov kws sau ntawv tau pom tias muaj cov txheej txheem ntawm ob X chromosomes ua rau lub cev hnyav dua rau cov rog rog piv rau ib qho X chromosome tsis hais tus naj npawb ntawm Y chromosomes [30]. Hauv cov neeg uas rog rog, muaj kev sib deev dimorphism nyob rau hauv cov theem ntawm adipokines thiab lawv correlation nrog metabolic ntshawv siab. Walicka et al. pom tias cov poj niam muaj ntau dua adiponectin, leptin, thiab visfatin. Hauv cov poj niam, muaj qhov cuam tshuam tsis zoo ntawm cov qib ntawm adiponectin thiab insulin thiab homeostasis qauv kev ntsuas ntawm insulin tsis kam (HOMA-IR) index. Nyob rau hauv lem, nyob rau hauv cov txiv neej, muaj ib tug zoo correlation ntawm theem ntawm leptin thiab HOMA-IR index [31]. Nws tau raug pom tias qhov sib piv ntawm leptin-rau-adipokine (Lep / Adpn) yog qhov qhia txog kev mob metabolic. Hauv kev tshawb fawb los ntawm Selthofer-Relatic et al., hauv cov poj niam, qhov piv txwv no zoo sib xws nrog kev ntsuas anthropometric. Hauv cov txiv neej, txawm li cas los xij, qhov siab dua Lep / Adpn piv, qhov tshwm sim ntawm tag nrho cov roj (cholesterol) phem, cov lipoprotein tsawg (LDL) feem, thiab TG yog. Qhov no qhia tias qhov sib txawv ntawm qhov tso tawm ntawm adipokines hauv kev sib deev sib txawv cuam tshuam rau kev ua haujlwm neurohormonal ntawm AT. Qhov no ua rau muaj qhov sib txawv ntawm cov metabolic profile [32].

Cov poj niam, yam tsawg kawg ua ntej cev xeeb tub, muaj kev tiv thaiv ntau dua ntawm kev rog thiab kev hloov pauv hauv AT. Lawv kuj muaj peev xwm tswj tau txoj haujlwm ntawm lub raum kom zoo. Thoob plaws txhua chav kawm ntawm CKD, cov txiv neej pom ntau lub raum puas thiab kev loj hlob sai rau cov kab mob raum kawg (ESRD) piv rau cov poj niam premenopausal. Tom qab menopause, cov nyhuv no hnav tawm [33].

5. Kev rog rog thiab mob raum mob

CKD txhais tau tias yog qhov cuam tshuam ntawm kev ua haujlwm lossis cov qauv ntawm lub raum kav ntev tshaj li peb lub hlis. CKD muab faib ua tsib theem raws li tus nqi ntawm glomerular filtration rate (GFR) [34]. Nws tau kwv yees tias qhov nruab nrab ntawm qhov tshwm sim thoob ntiaj teb ntawm CKD yog 13.4%, tab sis ntau tus neeg mob mus tsis tau kuaj pom thiab paub txog tus kab mob nyob rau theem kawg ntawm kev loj hlob [6].

Kev rog dhau thiab rog ua rau muaj kev loj hlob ntawm CKD ntawm 15-30% ntawm cov neeg mob, tab sis cov txheej txheem ntawm lub raum puas tsis nkag siab [35]. Kev rog rog ua rau muaj kev pheej hmoo ntawm kev tsim CKD ncaj qha thiab tsis ncaj, raws li qhia hauv daim duab 2. Cov nyhuv ncaj qha cuam tshuam nrog glomerular hyperfiltration (hloov siab GFR), nce lub raum plasma flow, microvascular stretching, renin-angiotensin-aldosterone system (RAAS) ua kom muaj zog. , hloov pauv secretion los ntawm AT, thiab lipotoxicity. Tag nrho cov xwm txheej no txhawb kev tsim ntawm o, oxidative kev nyuaj siab, thiab fibrosis hauv ob lub raum [11,36]. Cov txheej txheem pathophysiological tau piav qhia saum toj no ua rau kev txhim kho ntawm kev rog-txog glomerulopathy (ORG) thiab yog tus cwj pwm los ntawm glomerulomegaly. Yog tias nws nrog glomerulosclerosis, nws yog hu ua focal thiab segmental glomerulosclerosis (FSGS) [37]. Thawj cov tsos mob ntawm ORG feem ntau yog microalbuminuria lossis kho mob tseem ceeb proteinuria [38]. Cov kab mob no ua rau muaj kev puas tsuaj rau nephrons thiab kev loj hlob ntawm CKD. Qhov xwm txheej ntawm nws tsis tu ncua, txawm li cas los xij, vim qhov tsis tshua muaj lub raum biopsy tau ua, cov txheeb cais tseeb tsis paub [39,40]. Kev tshawb fawb tab tom nrhiav pom tshiab biomarkers ntawm lub raum puas. Ib qho ntawm lawv yog micro-RNA, uas tuaj yeem ntsuas hauv cov ntshav [41]. Qhov cuam tshuam ncaj qha ntawm CKD kev txhim kho yog cuam tshuam nrog ntshav siab, atherosclerosis, thiab ntshav qab zib hom 2 [35].

Hyperfiltration tshwm sim los ntawm kev nthuav dav ntawm afferent arteriole mus rau glomerulus, uas cuam tshuam nrog kev nce ntxiv ntawm cov piam thaj thiab sodium los ntawm sodium-glucose co-transporter-1 (SGLT1) thiab sodium-glucose co-transporter-2 (SGLT2). ), uas ua rau lub raum hypertrophy. Qhov tshwm sim yog tshwm sim los ntawm qhov nce ntawm qhov ntim ntawm glomerular tuft / capsule, tubular epithelium / lumen, thiab kev raug mob podocyte. Cov kev hloov no thiaj li ua rau glomerulosclerosis [42,43]. Lub physiological glomerular hyperfiltration tshwm sim tom qab noj cov protein ntau, thiab sodium, thiab thaum cev xeeb tub [44,45]. Glomerulomegaly yog lwm lub raum pathology cuam tshuam nrog kev rog rog uas tshwm sim ntawm nws tus kheej ntawm microalbuminuria. Cov txheej txheem no ua rau lub raum tsis ua haujlwm thiab cov teeb meem cuam tshuam nrog nws [11,45].

Lipotoxicity txhais tau tias yog ectopic tsub zuj zuj ntawm lipids hauv nruab nrog cev uas tsis yog AT. PRAT thiab tsub zuj zuj ntawm fatty acids nyob rau hauv lub raum parenchyma ua kev puas tsuaj rau turbulent interstitial cov ntaub so ntswg, proximal tubular epithelial hlwb, thiab endothelial hlwb [46]. Non-esterified fatty acid (NEFA) tsub zuj zuj ua rau insulin tsis kam thiab apoptosis ntawm podocytes uas tsis tuaj yeem rov tsim dua [39,47,48]. Insulin tsis kam thiab hyperinsulinemia ua rau kev ua kom lub paj hlwb ua haujlwm, uas tau lees paub los ntawm kev nce hauv cov ntsiab lus ntawm catecholamines, thiab ua rau muaj qhov tshwm sim ntawm vasoconstriction [49]. Cumulation ntawm NEFA nyob rau hauv lub raum hlwb activates macrophages, uas ua rau transformation mus rau hauv lub hlwb ua npuas ncauj [46]. Lub raum steatosis ua rau kev txhim kho ntawm o thiab fibrosis. Lipotoxicity ua rau txo qis ntawm adenosine 50 -triphosphate (ATP) los ntawm inhibition ntawm -oxidation, yog li ua rau cov qauv ntawm mitochondria [50]. PRAT compresses lub raum, uas ua rau muaj kev nce hauv hydrostatic siab, txo cov ntshav hauv lub raum, thiab ua rau CKD [51]. Kev cuam tshuam ntawm adipokines ntawm kev pheej hmoo ntawm kev tsim CKD tau piav qhia hauv tshooj tom ntej.

Daim duab 2. Qhov cuam tshuam ncaj qha thiab tsis ncaj ntawm kev rog ntawm kev loj hlob ntawm cov kab mob raum ntev. Cov ntawv luv: RAAS-renin-angiotensin-aldosterone system; PRAT-perirenal adipose cov ntaub so ntswg

6. Adipokines thiab Lawv cuam tshuam rau Pathogenesis, Kev Noj Qab Haus Huv Kev Noj Qab Haus Huv, thiab Kev pheej hmoo ntawm cov hlab plawv hauv cov kab mob raum.

6.1. Leptin

Leptin yog plasma protein encoded los ntawm cov noob rog rog (ob) uas tau piav qhia thawj zaug hauv xyoo 1994. Nws yog ib qho tshuaj anorexigenic uas ua rau muaj kev siv zog ntau ntxiv. Hauv kev rog rog, qhov nce ntxiv ntawm leptin tshwm sim, ib txhij nrog leptin tsis kam [52]. Txo kev ua haujlwm ntawm leptin hauv hypothalamus impairs qab los noj mov [53].

Enlarged adipocytes yog tus cwj pwm los ntawm kev tso zis ntau ntxiv ntawm leptin. Yog li, adipokine, los ntawm kev khi rau leptin receptors nyob rau hauv lub hauv paus paj hlwb, ua rau muaj zog ua hauj lwm ntawm lub paj hlwb, uas, yog li ntawd, yuav ua rau rog rog-txog ntshav siab [34]. Ntshav siab yog inextricably txuas nrog raum tsis ua haujlwm. Txawm hais tias kub siab yog ib qho ntawm cov kev pheej hmoo loj tshaj plaws rau kev txhim kho CKD, nws kuj yog qhov tshwm sim ntawm lub raum tsis ua haujlwm. Qhov no tau tshwm sim los ntawm qhov tseeb tias nrog kev nce qib ntawm CKD, qhov tshwm sim ntawm kev kub siab nce [54]. Leptin tsub kom qhov kev nthuav qhia ntawm kev hloov pauv kev loj hlob zoo tshaj - 1 (TGF- 1) noob thiab lwm yam fibrotic yam, xws li collagen IV thiab fibronectin, uas txhawb nqa lub pro-liferation ntawm mesangial hlwb hauv ob lub raum [55] . Kev tsim tawm ntau dhau ntawm cov hlwb tuaj yeem ua rau glomerulosclerosis los ntawm mesangial hypertrophy hauv glomeruli, thickening ntawm glomerular qab daus daim nyias nyias, thiab nce extracellular matrix [11]. Nyob rau hauv lem, glomerulosclerosis, los ntawm kev nce permeability ntawm glomerular barrier, pab txhawb rau proteinuria thiab impaired raum ua haujlwm [56]. Leptin-induced vascular endothelial dysfunction yog lwm lub tswv yim uas txuas hloov pauv adipokine secretion hauv kev rog nrog rau lub raum tsis ua haujlwm. Leptin nkoos tsim ntawm reactive oxygen hom (ROS) uas impairs vascular teb rau acetylcholine, yog li pib txo bioavailability ntawm nitric oxide thiab oxidative kev nyuaj siab [57]. Tsis tas li ntawd, leptin modulates lub cev tiv thaiv kab mob. Cov tshuaj hormones nce tus naj npawb ntawm T-helper hlwb thiab txo tus naj npawb ntawm Treg. Nws kuj tseem ua rau phagocytic kev ua ntawm macrophages thiab nce TNF-, IL-6, thiab interleukin 12 (IL-12). Nyob rau hauv cov ntaub ntawv ntawm hyperleptinemia, qhov sib npaug ntawm cov txheej txheem pro- thiab kev tiv thaiv kab mob yog cuam tshuam thiab o tshwm sim [58].

Hauv CKD, metabolic degradation nyob rau hauv lub raum tubules thiab glomerular filtration yog cuam tshuam, uas ua rau kom nce nyob rau hauv cov concentration ntawm leptin nyob rau hauv cov ntshav. Qhov concentration ntawm leptin nce nrog kev loj hlob ntawm tus kab mob [11,59,60]. Korczy 'nsk et al. pom tau hais tias muaj kev nce ntxiv ntawm leptin hauv cov ntaub so ntswg subcutaneous adipose (SAT) ntawm 5th-theem CKD pre-dialysis thiab dialyzed cov neeg mob [61]. Hauv theem 3-5 ntawm CKD, tsis muaj kev lim ntshav, hloov pauv adipokines profile thiab insulin tsis kam raug cuam tshuam nrog VAT, SAT, thiab cov rog intrahepatic [62]. Leptin qib siab dua hauv cov poj niam hemodialysis (HD) dua li cov txiv neej HD [63]. Leptin cuam tshuam txog kev noj zaub mov zoo thiab CVR ​​ntawm cov neeg mob tau hais. Cov neeg mob nrog CKD muaj kev pheej hmoo ntawm kev tsim PEW, uas cuam tshuam nrog kev pheej hmoo ntawm kev tuag. Feem ntau ntawm PEW ntawm cov neeg mob dialyzed yog li 80% [64]. Ib qho ntawm cov txheej txheem cuam tshuam rau lawv qhov tshwm sim yog leptin concentration cuam tshuam. Leptin muaj cov khoom catabolic xws li nce cov metabolic tus nqi thiab inducing anorexia [65,66]. Kev tso tawm ntawm neuropeptides thiab neurotransmitters koom nrog hauv kev tswj hwm kev noj qab haus huv tshwm sim los ntawm Janus Kinase-2 (JAK2) ua kom tshwm sim los ntawm kev koom tes ntawm leptin nrog nws cov receptors (ObRb). Leptin tsub kom lub secretion ntawm -melanocyte-stimulating hormone (-MSH) thiab cocaine- thiab amphetamine-regulated transcript (CART), stimulating lub siab ntawm satiety, inhibits lub synthesis ntawm secretion ntawm ib tug muaj zog appetite stimulants, piv txwv li, neuropeptide Y ( NPE) [67–69]. Cov concentration ntawm cov ntshav NPY nce, tab sis cerebrospinal kua (CSF) NPY txo qis nrog kev loj hlob ntawm CKD. Ib qho qis qis ntawm CSF NPY tau cuam tshuam nrog cachexia, txo lub zog kom tsawg, thiab cov nqaij ntshiv ntawm cov neeg mob CKD [70]. Nws tau raug pom tias cov ntshav qab zib ntau dua NPY prognosticate mob plawv tuag ntawm cov neeg mob lim ntshav [71,72]. Kev tshawb fawb kuj tau pom tias qib siab ntawm leptin ntawm cov neeg mob CKD cuam tshuam nrog kev tsis txaus lub zog thiab kev noj cov protein, thiab tseem txo qis cov leeg nqaij [9]. Markaki et al. pom tias cov qib leptin siab dua hauv HD thiab cov neeg mob ntshav qab zib peritoneal tau cuam tshuam nrog cov rog rog ntau dua (FMI) thiab poj niam txiv neej [73]. Ntawm qhov tod tes, lwm cov kev tshawb fawb qhia tias cov neeg mob PEW muaj cov qib leptin qis, uas tuaj yeem cuam tshuam txog cov rog rog tsawg. Cov qib Leptin muaj kev cuam tshuam zoo nrog cov cim inflammatory, uas tseem cuam tshuam rau txoj kev pheej hmoo ntawm kev noj zaub mov tsis zoo [74,75]. Kev tshawb fawb ntxiv yog xav tau kom nkag siab txog cov txheej txheem uas leptin cuam tshuam qhov tshwm sim ntawm PEW.

Nws tau raug pom tias cov ntshav qab zib ntau dua NPY prognosticate mob plawv tuag ntawm cov neeg mob lim ntshav. Leptin pab txhawb rau CVD los ntawm kev ua rau oxidative kev nyuaj siab, o, thiab endothelial cell proliferation [76]. Qhov no adipokine nce platelet aggregation thiab cuam tshuam cov concentration ntawm vascular endothelial kev loj hlob yam (VEGF), uas ua rau angiogenesis. Vascular endothelial dysfunction ua rau txoj kev loj hlob ntawm atherosclerosis, uas yog lub hauv paus ntawm ntau yam kab mob plawv [60,77]. Tsis tas li ntawd, leptin txhawb lub plawv hypertrophy los ntawm mitogen-activated protein kinase (MAPK) signaling [78].

Lu et al. observed that higher serum leptin levels among patients with CKD were a risk factor for aortic stiffness, measured as the carotid-femoral pulse wave velocity (cfPWV). The study was conducted among 205 patients with CKD stage 3–5 without dialysis and kidney transplantation (KT). Other risk factors for aortic stiffness were higher systolic blood pressure (SBP) and older age [79]. Similar research results were obtained in HD patients and those after KT. In addition, in Kuo et al.'s study, elevated serum leptin level among HD patients was correlated with body mass index (BMI) and fat mass [80,81]. One study found that leptin levels were associated with CVR among HD patients only with a larger waist circumference (>102 cm) [82] mus.

Txawm li cas los xij, qis leptin concentration yog ib qho kev kwv yees ntawm kev tuag ntawm cov neeg mob CKD. Qhov no tau lees paub hauv kev tshawb fawb tau ua rau HD cov neeg mob thiab cov neeg tau txais kev hloov raum (KTRs). Txoj kev tshawb fawb nrog 1214 KTRs tau pom tias, txawm hais tias muaj kev cuam tshuam tsis zoo ntawm qib leptin siab ntawm kev ua haujlwm ntawm graft thiab mob hnyav, qhov kev pheej hmoo ntawm kev tuag yog 10% qis dua rau txhua 10 ng / mL siab dua leptin concentration [83,84]

6.2. Adiponectin

Adiponectin, 244 amino acid protein, ua lub luag haujlwm tseem ceeb hauv insulin rhiab heev los ntawm kev ua kom fatty acid oxidation thiab txo gluconeogenesis. Adiponectin muaj ob hom receptors-adipoR1 thiab adipoR2 [85,{5}}]. Tus qub yog pom nyob rau hauv tag nrho cov ntaub so ntswg thiab tom kawg mas nyob rau hauv daim siab. Cov adipoR1 receptors nyob rau hauv lub excretory system yog tam sim no nyob rau hauv lub proximal tubule hlwb thiab glomerulus hlwb, piv txwv li, nyob rau hauv lub hlwb ntawm endothelium, podocytes, mesangium, thiab lub epithelium ntawm Bowman's capsule. Adiponectin hla lub glomerular filtration barrier, khi rau adipoR1 receptor ntawm cov qauv saum toj no, thiab ua rau lawv los ntawm kev ua kom cov adenosine monophosphate-activated protein kinase (AMPK) txoj hauv kev [86]. AMPK stimulation induces ATP tsim cov txheej txheem, suav nrog fatty acid oxidation, uas tiv thaiv kev rog thiab metabolic ntshawv siab, thiab yog li tiv thaiv tsis ncaj ncees lawm kev ua haujlwm ntawm lub raum. Txawm li cas los xij, hauv kev rog rog, qhov concentration ntawm adiponectin txo qis. Lub raum raug cuam tshuam los ntawm cov teebmeem ntawm kev nce qib ntawm pro-inflammatory adipokines thiab tsis muaj kev tiv thaiv los ntawm adiponectin. Adiponectin kuj tseem tuaj yeem ua lub luag haujlwm hauv kev txhim kho kev rog ntawm albuminuria [86–88].

Qhov txo qis ntawm adiponectin ua rau kev hloov pauv ntawm zonula occludens (ZO-1) cov proteins los ntawm cov txheej txheem podocyte epithelial mus rau hauv cytosol. ZO-1 cov proteins yog cov txheej txheem nruj-hluav taws xob cov proteins uas yog lub luag haujlwm rau kev nruj ntawm cov epithelium thiab kev ua haujlwm kom zoo ntawm cov kab diaphragms. Lub slit diaphragm yog cov qauv pom nyob nruab nrab ntawm cov txheej txheem ntawm ko taw ntawm cov podocytes thiab ua raws li lub sieve los tiv thaiv cov proteins uas hnyav molecular los ntawm kev nkag mus rau hauv cov zis. Cov txheej txheem proteins ntawm slit diaphragms yog nephrin thiab podocin, uas txiav txim siab qhov kev ua haujlwm zoo ntawm cov qauv no. Tsis tas li ntawd, qib qis ntawm adiponectin tau cuam tshuam nrog qis qis ntawm nephrin nyob rau hauv lub raum cortex, uas ua rau kom cov permeability ntawm cov teeb meem pom [89]. Adiponectin muaj qhov sib txawv ua rau leptin. Contrary to the action of leptin, txo cov theem ntawm adiponectin ua rau muaj zog synthesis ntawm TGF- 1. Qhov no ua rau cov cell hypertrophy thiab nce collagen synthesis, uas ua rau lub raum fibrosis [90].

Adiponectin muaj kev tiv thaiv ntawm vascular endothelium. Nws inhibits qhov kev txiav txim ntawm endothelial transcription factor-nuclear factor-kappa (NF-κ), los ntawm kev ua kom AMPK. Qhov txo qis hauv NF-κ kev ua haujlwm hauv endothelium inhibits qhov kev qhia ntawm pro-inflammatory adhesion proteins xws li vascular cell adhesion molecule-1 (VCAM-1), E-selectin, thiab intercellular adhesion molecule{{8 }} (ICAM-1). Nws ua rau cov adhesion ntawm monocytes mus rau endothelium ntawm cov hlab ntsha, uas yog lub ntsiab lus tseem ceeb hauv kev loj hlob ntawm atherosclerosis. Ntawm qhov tod tes, qhov no cuam tshuam ncaj qha rau lub raum cov qauv. Yog tias qhov kev puas tsuaj rau cov hlab ntsha tshwm sim hauv ob lub raum, nws ua rau txo qis hauv cov ntshav thiab cov ischemia hauv zos. Nws ua rau cell tuag los yog puas rau lawv cov qauv thiab lub raum puas. Ntawm qhov tod tes, cov txheej txheem inflammatory txuas ntxiv ua rau lub raum tsis ua haujlwm [91].

Tsis tas li ntawd, qhov qis qis ntawm adiponectin ua rau muaj kev ua kom muaj zog ntawm NADPH oxidase 4 (Nox4) thiab tsim cov oxidative kev nyuaj siab [92]. Ntau dhau ntawm ROS tsim los ntawm mitochondria tuaj yeem ua rau muaj kev puas tsuaj ntawm tes thiab ua rau lub raum tsis ua haujlwm [93]. Qib Adiponectin txo qis hauv kev rog rog, atherosclerosis, thiab metabolic syndrome. Txawm hais tias feem ntau tshwm sim ntawm cov kab mob metabolic, cov neeg mob CKD kho conserva tiv thaiv muaj los ntawm ob mus rau peb zaug ntau dua cov ntshav adiponectin piv rau cov neeg noj qab haus huv. Hauv cov neeg mob uas xav tau kev lim ntshav, qhov concentrations ntau dua [94,95]. Tom qab ua tiav KT, qib adiponectin txo qis [96].

Adiponectin cuam tshuam rau kev noj haus thiab CVR ​​ntawm cov neeg mob CKD. Kev nce qib hauv cov ntshav adiponectin yog txuam nrog qis BMI, lub duav ncig, qib albumin, poj niam txiv neej, thiab hnub nyoog laus dua [97-99]. Inverse koom haum kuj tau pom ntawm qib adiponectin thiab SAT, VAT, tag nrho lub cev rog, thiab lean lub cev hnyav [100]. Ntxiv mus, cov kev tshawb fawb qhia txog qhov tsis zoo ntawm cov qib adiponectin thiab tuav tes [101]. Adiponectin kuj tseem tuaj yeem cuam tshuam cov pob txha. Nws tau raug pom nyob rau hauv cov neeg mob HD tias qib siab dua ntawm adiponectin cuam tshuam nrog kev poob ntawm cov pob txha pob txha pob txha [102]. Qhov siab ntawm adiponectin tuaj yeem cuam tshuam txog kev noj zaub mov tsis zoo, uas qhia tau tias tsis zoo. Hyun et al. soj ntsuam cov khoom noj khoom haus thiab adiponectin concentration hauv 1303 cov neeg mob ua ntej lim ntshav. Raws li kev soj ntsuam rov qab, qib adiponectin ntau dua tau cuam tshuam nrog PEW ywj pheej ntawm ntau lwm yam [103]. Hauv lwm txoj kev tshawb fawb tau ua ntawm cov neeg mob lim ntshav, qhov kev sib raug zoo ntawm adiponectin thiab Malnutrition Inflammation Score (MIS) tau pom, uas qhia tias kev noj zaub mov tsis zoo [104,105].

Cov txiaj ntsig kev tshawb fawb txog kev cuam tshuam ntawm adiponectin ntawm CVR yog qhov tsis lees paub. Nws tau txiav txim siab tias qib siab ntawm adiponectin yuav tsum tau txais txiaj ntsig zoo rau kev noj qab haus huv ntawm cov neeg uas muaj CKD, uas tau lees paub hauv ntau cov kev tshawb fawb uas cov qib adiponectin qis dua tau cuam tshuam nrog kev tshwm sim ntau dua ntawm cov xwm txheej hauv plawv [106-108]. Ntawm qhov tod tes, cov kev tshawb fawb sib txawv tau pom tias qib siab ntawm cov adipokine no cuam tshuam nrog kev pheej hmoo ntawm kev tuag ntau dua, suav nrog CVR. Li no, nws yog qee zaum hu ua "adiponectin paradox" [109]. Menon et al. qhia tau hais tias kev nce hauv serum adiponectin ntawm theem 3-4 ntawm CKD los ntawm 1 µg / mL yog txuam nrog 6% siab dua CVR [110]. Hauv MADRAD txoj kev tshawb fawb ntawm 501 HD cov neeg mob, qib adiponectin siab dua kuj tseem cuam tshuam nrog kev pheej hmoo ntawm kev tuag ntau dua. Ntxiv mus, qhov concentration ntawm adiponectin tau zoo cuam tshuam nrog high-density lipoprotein (HDL) thiab tsis zoo cuam tshuam nrog tag nrho cov cholesterol thiab LDL [100]. Cov qib siab ntawm adiponectin kuj tseem txuas nrog macroalbuminuria, uas yog qhov tsis zoo ntawm cov hlab plawv plawv [111]. Ib qho kev sib koom ua ke ntawm siab adiponectin concentration thiab qis BMI ntawm CVR tau pom [112]. Lub mechanism ntawm qhov cuam tshuam ntawm adiponectin ntawm CVR tsis paub. Adipokine tuaj yeem ua rau muaj qhov tshwm sim ntawm qhov mob, cuam tshuam nrog hematopoiesis, thiab ua kom cov concentration ntawm atrial natriuretic peptide (ANP) thiab hlwb natriuretic peptide (BNP), uas yog cov cim qhia ntawm lub plawv tsis ua haujlwm [113,114].

Nws tau raug tsim los tias Lep / Adpn piv yuav yog qhov qhia tau zoo dua ntawm kev pheej hmoo ntawm kev tsim CVD thiab kev tuag hauv cov neeg mob CKD dua li qhov concentration ntawm adiponectin lossis leptin ib leeg. Lep / Adpn piv qhia txog kev cuam tshuam ntawm cov ntaub so ntswg adipose [115]. Frühbeck et al. npaj qhov sib piv: adiponectin-to-leptin (Adpn / Lep). Qhov qis Adpn / Lep piv tau cuam tshuam nrog nce o thiab qhov tshwm sim ntawm oxidative kev nyuaj siab, uas ua rau muaj kev pheej hmoo ntawm CVD [116].