Nicotine Exacerbates Tacrolimus-induced Renal Injury Los ntawm Programmed Cell Tuag
Mar 23, 2022
Hu rau:joanna.jia@wecistanche.com/ WhatsApp: 008618081934791
Yu Ji Jiang, Sheng Cui, Kang Luo, Jun Ding
Taw qhia
Txawm hais tias qhov kev tshawb pom ntawm cov tshuaj tiv thaiv kab mob tshiab, tacrolimus (TAC) tseem yog lub hauv paus ntawm cov tshuaj tiv thaiv kab mob hauv cov khoom hloov pauv hauv lub cev. Txawm li cas los xij, kev siv TAC mus ntev ua rau muaj kev pheej hmoo ntawm kev tsis zoo (xws li nephrotoxicity, neurotoxicity, kab mob, malignancies, ntshav qab zib, thiab kev tsis txaus siab ntawm plab hnyuv) [1]. Ntawm cov no, mobraumraug moblos yog mob ntev TAC nephrotoxicity tau tshaj tawm hauv 46 feem pua ntawm cov neeg tau txais kev kho lub ntsws [2] thiab 22.4 feem pua ntawm cov neeg tau txais kev hloov lub raum [3]. Thaum mobraumraug mobraug suav hais tias thim rov qab tom qab TAC koob tshuaj txo qis lossis kev tshem tawm tag nrho, mob nephrotoxicity, uas ua rau poob allograft, tsis tuaj yeem thim rov qab. Tus kab mob TAC nephrotoxicity yog tus cwj pwm los ntawm glomerulopathy, hyalinosis ntawm afferent arterioles, thiab striped tubulointerstitial fibrosis (TIF) [4]. Txawm hais tias qhov tseeb ntawm qhov kev kuaj mob no tseem tsis tau paub, peb tsis ntev los no tau pom tias oxidative stress-originated inflammatory, transforming growth factor 1 (TGF- 1), and programmed cell death may be important players [5]. Kev haus luam yeeb yog ib qho kev sib tw tseem ceeb rau pej xeem kev noj qab haus huv thiab lub luag haujlwm nyiaj txiag hauv zej zog uas txo cov kev ua neej zoo. Cov ntaub ntawv qhia txog kab mob kis tau qhia tias tam sim no muaj ntau tshaj li ib lab tus neeg haus luam yeeb thoob ntiaj teb thiab rau lab tus neeg tuag txhua xyoo vim kev haus luam yeeb. Cov nqi no yog ob qho tib si nce, tshwj xeeb tshaj yog nyob rau hauv cov teb chaws tsim lossis tsis tau tsim tawm [6]. Nws tau pom zoo tias kev haus luam yeeb yog qhov muaj feem cuam tshuam rau ntau hom mob qog noj ntshav, kab mob plawv (myocardial infarction thiab stroke), thiab kab mob ntsws obstructive. Hauv lub raum, kev haus luam yeeb ua rau lub raum tsis ua haujlwm hnyav hauv cov neeg mob ntshav qab zib, kub siab, polycystic.raumkab mob, thiab tom qab lub raum hloov [7]. Ntxiv mus, kev haus luam yeeb kuj tuaj yeem ua rau de novo raum puas txawm tias nyob hauv cov neeg noj qab haus huv uas tsis muaj kab mob raum ua ntej (CKD) [8]. Txoj kev tshawb no nrhiav kev ntsuam xyuas: (1) sebnicotine(NIC), uas yog ib feem tseem ceeb ntawm kev haus luam yeeb, ua rau TAC ua rau lub raum raug mob; thiab, yog tias muaj, (2) uas mechanism tso nyiaj rau NIC (nicotine)-accelerated nephrotoxicity.
cistanches herba tuaj yeem txo lub raum ua haujlwm
TSEEM CEEB
Effect of NIC(nicotine)nyob rau hauv parameters
Table 1 qhia txog cov teebmeem ntawm NIC(nicotine)ntawm cov kev tsis tseem ceeb hauv pawg sim. Ob leeg NIC(nicotine)thiab TACincrease UV (polyuria), uas tau ntxiv los ntawm NIC(nicotine)thiab TAC kev kho mob. Neither NIC(nicotine)tsis yog TAC tiv thaiv BW poob. Cov zis tso zis tawm protein ntau, Scr, BUN, thiab Cys-C tau pom ntau dua hauv NIC.(nicotine)thiab TAC pawg piv nrog VH pawg; cov qib no tau nce ntxiv nrog kev sib xyaw ntawm ob cov tshuaj, txhais tau tias NIC(nicotine)accelerates TAC-vim lub raum tsis ua haujlwm. Tsis muaj qhov sib txawv ntawm pawg SBP qhov sib txawv. Plaub-lub lim tiam TAC kev kho mob nce ntshav TAC concentration rau 11.0±og ng/mL, thaum NIC(nicotine) did not influence blood TAC concentration(12.8±15 ng/mL,p>o.o5 vs. TAC). Tsis tas li ntawd, kho cov nas ib txwm nrog NIC(nicotine)Qhov tshwm sim-ed hauv cov ntshav thiab cov zis cotinine concentration nce 56.5 ± 17 ng / mL thiab 8; 6 ± 192.6 ug / hnub, feem. Cov ntshav qab zib thiab cov zis cotinine concentrations ua raws li cov kev pom hauv tib neeg uas yog cov neeg haus luam yeeb [13].
Table 1. Cov nyhuv ntawm NIC(nicotine)ntawm functional parameters
Effect of NIC(nicotine)Nyob rau hauv histopathology nyob rau hauv mob TAC nephrotoxicity
Tus kab mob TAC nephrotoxicity yog tus cwj pwm los ntawm cov cim histological xws li striped TIF thiab glomerupathies. Los ntawm histological staining thiab electron microscopy, peb pom tias TAC-ua rau glomerular raug mob yog tshwm sim los ntawm glomerular qab daus thickening thiab effacement ntawm podocyte ko taw txheej txheem (Fig. IA, IC, thiab D), qhov no yuav txuas mus rau increment urine protein excretion. Ntawm kev txheeb xyuas ntau, ob qho tib si NIC(nicotine)thiab TAC tau nce thaj tsam mesangial, nrog rau kev nce ntxiv hauv NIC(nicotine)thiab TAC group. Cov kev hloov pauv loj hauv TAC nephrotoxicity ntev tau raug kaw rau cov cheeb tsam tubulointerstitial, raws li tau piav qhia los ntawm tubulointerstitial fibrous deposition, tubular atrophy, thiab striped fibrosis (Fig.1B,1E, thiab F). Cov duab qhia meej tias TIF cov qhab nia hauv NIC(nicotine)ntxiv rau TACgroup tau siab dua hauv NIC(nicotine)pab pawg los yog TACgroup.
Daim duab 1. Tus neeg sawv cev photomicrographs ntawm periodic acid-Schiff(PAS)(A), Masson trichrome (B), kis electron mi-croscopy (CF), thiab kev soj ntsuam ntau ntawm glomerular raug mob thiab tubulointerstitial fibrosis (TIF); (C) glomerular hauv qab daus membrane thickening ( xub); (D) effacement ntawm podocyte ko taw txheej txheem (xub xub); (E) o ntawm tubulointerstitium thiab nws kim heev collagen deposition (scatters); (F) atrophied tubules ( xub xub).VH, tsheb; NIC(nicotine), nicotine; TAC, tacrolimus. p
Effect of NIC(nicotine)ntawm profibrotic cytokine qhia nyob rau hauv ntev TAC nephrotoxicity
Txoj kev tshawb no nrhiav los sib piv cov lus qhia ntawm profibrotic cytokine TGF- 1 thiab CTGF, thiab cov extracellular matrix (ECM) feem ntawm ig-h; nruab nrab ntawm cov pab pawg sim. Raws li kev tshawb pom TIF, NIC(nicotine)augmented TAC-induced overexpression ntawm pro-fibrotic TGF- 1thiab CTGF thiab ECM ig-h3(Fig.2)
Daim duab 2. Tus sawv cev photomicrographs ntawm immunoblotting tsom xamrau (A) hloov pauv txoj kev loj hlob 1 (TGF-B1), (B TGF- -induced gene-h(ig-h3), thiab (C) connective tissue growth factor(CTGF). Cov txiaj ntsig rau kev qhia cov protein yog sawv cev. siv lub tsheb (VH) pab pawg raws li 1oo feem pua qhia thiab normalized rau -actin. NIC(nicotine), nicotineTAC, tacrolimus. 3 ua p
Effect of NIC(nicotine)ntawm o nyob rau hauv ntev TAC nephrotoxicity
Txhawm rau txheeb xyuas cov txiaj ntsig ntawm NIC ntawm kev mob hauv TAC-vim lub raum raug mob, peb tau kawm txog kev qhia ntawm proinflammatory mediators thiab pyroptosis-cuam tshuam cov noob los ntawm immunoblotting thiab immunohistochemistry. Daim duab 3 tau pom tias kev kho TAC tau kho qhov kev qhia ntawm pyroptosis-txog cytokines (ⅡL-1, IL-18, thiab NLRP3) thiab MCP-1, ua rau ED-1- zoo cell infiltration, thiab kev nce ntxiv tau pom los ntawm kev kho mob ua ke ntawm NIC(nicotine)thiab TAC.
Daim duab 3. Cov neeg sawv cev photomicrographs ntawm immunohistochemistry rau ectodermal dysplasia-1 (ED-1)(A) thiab immunoblot-ting tsom xam rau proinflammatory cytokines (B). VH, tsheb; NIC(nicotine), nicotine; TAC, tacrolimus; MCP-1, monocyte chemotactic protein-1;IL, interleukin; NLRP3, NOD-zoo li receptor pyrin domain-muaj protein3. p
Effect of NIC(nicotine)ntawm oxidative kev nyuaj siab nyob rau hauv ntev TAC nephrotoxicity
Raws li qhia hauv Fig.4, ntev(nicotine)TAC kev kho mob zoo sib xws nrog qhov tsis sib xws ntawm oxidant thiab antioxidant enzymes [12,14. Immunoblotting tsom xam pom tau tias NIC upregulated TAC-induced NOX-2 thiab NOX-4 qhia tab sis suppressed SOD1 thiab SOD2 kab lus. Tsis tas li ntawd, cov ntshav qab zib thiab cov zis ntawm 8-OHdG, tus cim kev ntxhov siab oxidative, tau siab dua hauv pawg NIC thiab TAC piv nrog cov pab pawg VH thiab siab tshaj hauv pawg NIC ntxiv rau TAC. Cov kev tshawb pom no qhia txog kev sib koom ua ke ntawm NIC thiab TAC ntawm kev ntxhov siab oxidative hauv cov qauv no.
Daim duab 4.Tus neeg sawv cev photomicrographs ntawm immunoblotting tsom xam ntawm oxidative stress-related proteins (A) thiab ntshav (B) thiab zis (C)8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations. VH, tsheb; NIC(nicotine), nicotine; TAC, tacrolim-us; SOD, superoxide dismutase; NOX, NADPH oxidase.Bp
Effect of NIC(nicotine)ntawm programmed cell tuag nyob rau hauv ntev TAC nephrotoxicity
Ob hom I (apoptosis) lossis hom II (autophagy) programmed cell tuag yog koom nrog hauv pathogenesis ntawm TAC-vim lub raum raug mob [1s]. Siv TUNEL kev soj ntsuam, peb tau pom tias feem ntau TUNEL-zoo hlwb los yog lub cev apoptotic tau nyob rau hauv tubular epithelial hlwb thiab interstitial vascular endothelial hlwb, qhov twg tubular atrophy thiab raug TIF zuj zus (Fig.5A). Kev soj ntsuam ntau pom tau tias ob qho tib si NIC(nicotine) thiab TAC tau nce TUNEL-zoo hlwb piv nrog VH pawg; qhov no tau tshaj tawm hauv NIC ntxiv rau TAC pawg. Ntawm qib molecular, qhov sib ntxiv ntawm NIC(nicotine)rau TAC-kho nas ua rau muaj teeb meem loj ntawm Bcl-2/Bax thiab cleaved caspase-3 qhia txog kev tuag ntawm tes (Fig. 5B). Tsis tas li ntawd, electron microscopy pom tias TAC kev kho mob ua rau muaj kev tsim ntau ntawm autophagic compartments, xws li pib autophagic vacuoles (AVi), degradative autophagic vacuoles (Avd), thiab mitophagy (ib hom kev xaiv autophagy) hauv NIC, TAC, thiab NIC. ntxiv rau TAC pawg (Fig. 6). Quantitative immunoblotting qhia tias overexpression p62, LC3B, PINK1, thiab Parkin proteins pom nyob rau hauv TAC-kho nas raum tau ntxiv nrog NIC (Fig.6G thiab 6H).
Daim duab 5. Tus neeg sawv cev photomicrographs ntawm TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay(A) thiab tshuaj tiv thaiv kab mob tiv thaiv kab mob rau apoptosis-tswj cov noob (B).Nicotinekev kho mob tsub kom TUNEL-zoo hlwb (xub xub) nyob rau hauv lub tacro-limus-kho nas raum.VH, tsheb; NIC(nicotine)nicotine; TAC, tacrolimus; Bcl, B-celllymphoma; Bax, Bcl2-associated X. p
Effect of NIC(nicotine)ntawm mitochondrial tsis ua hauj lwm nyob rau hauv ntev TAC nephrotoxicity
Los ntawm kev xa hluav taws xob microscopy, peb pom meej tias ob qho tib si NIC(nicotine)thiab TAC rhuav tshem mitochondrial architectures, raws li qhia los ntawm kev txo qis mitochondrial loj thiab tus naj npawb, disorganized cristae, vacuolization, fusion, mitophagy tsim, thiab mitochondria muab faib ua ob lossis peb tus ntxhais organelle fission)(Fig.6). Cov txiaj ntsig kev tshawb fawb pom tau tias NIC(nicotine) kev kho mob ntxiv txo tus naj npawb thiab qhov loj ntawm mitochondria piv nrog NIC lossis TAC kev kho mob ib leeg. Immunoblotting tsom xam qhia tias dysregulation ntawm mitochondrial-related proteins (OPA1 thiab Drpi) induced los ntawm Nicor TAC yog exacerbated los ntawm coadministration ntawm NICand TAC (Fig. 6).
Daim duab 6. Tus neeg sawv cev kis tau tus mob electron micrographs ntawm autophagy thiab mitochondrial morphology(AF), immunoblot-ting analysis (G, H), thiab qhov ntau ntawm mitochondrial tus naj npawb thiab qhov loj me hauv txhua pab pawg kho mob. (A) Autophagy tsim nyob rau hauv ob lub raum ntawm tacrolimus (TAC) thiab/los yognicotine(NIC) kho nas ( xub); (B) ib qho chaw autophagic uas muaj mitochondria lub raum ntawm 'TAC thiab / lossis NIC(nicotine)kho nas (mitophagy, xub); (C) ib txwm mitochondria; (D) txo tus lej mitochondrial hauv ob lub raum ntawm TAC thiab / lossis NIC(nicotine)kho nas; (E) mitochondrial fusion pom nyob rau hauv ob lub raum ntawm TAC thiab / los yog NIC kho nas (lub voj voog); (F) mitochondrion muab faib ua ob los yog ntau tshaj tus ntxhais organelles nyob rau hauv lub raum ntawm TAC thiab / los yog NIC kho nas (fission, voj voog) . VH, tsheb; LC3B, lub teeb saw 3B; PINK1, phosphate thiab nro homolog tshem tawm ntawm chromosome kaum-induced kinase 1; OPA, optic atrophy protein; Drp, dynamin-related protein.p
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Effect of NIC(nicotine)ntawm endoplasmic reticulum kev nyuaj siab nyob rau hauv ntev TAC nephrotoxicity
Raws li pom nyob rau hauv Fig.7, Nicor TAC induced degranulation ntawm ribosomes, disconnected thiab dilated cisternae, thiab peroxisome vacuolization nyob rau hauv lub ntxhib endoplasmic reticulum (ER), whereas smooth ER qauv tseem yuav luag li qub (Fig.7B). Immunoblotting tsom xam pom tias yog NIC(nicotine)los yog TAC tau nce qhov kev qhia ntawm ER kev ntxhov siab txog cov noob suav nrog CHOP, Bip, IRE-1 , thiab ATF-6, tab sis lawv cov lus tau nce ntxiv los ntawm kev sib xyaw ntawm ob (Fig.7C).
Daim duab 7. Cov neeg sawv cev photomicrographs ntawm kis tau tus mob electron microscopy (A, B) thiab immunoblotting tsom xam ntawm endo-plasmic reticulum (ER) kev ntxhov siab ntsig txog noob (C).(A) Ib txwm ntxhib ER ( xub); (B) ribosomes degranulation, disconnected thiab dilated cisternae, thiab vesicle dilatation ntawm ntxhib ER nyob rau hauvnicotine(NIC) thiab/los yog tacrolimus (TAC)-kho nas raum. VH, tsheb; CHOP, C / EBP homologous protein; Bip, khi immunoglobulin protein; IRE-1c,inositol-yuav tsum muaj protein ntau-1c; ATF, acti-vating transcription factor. p< o.01="" vs.vh,="">
Kev sib tham
Kev haus luam yeeb yog ib qho tseem ceeb hloov pauv qhov kev pheej hmoo rau kev loj hlob ntawm CKD hauv ob qho tib si cov neeg noj qab haus huv thiab cov neeg mob uas muaj kab mob hauv qab (xws li, ntshav qab zib, ntshav siab). Kev sim tshuaj ntsuam xyuas pom tias kev haus luam yeeb ua rau cov zis albumin tso tawm thiab cuam tshuam rau lub raum ua haujlwm [16]; Tsis tas li ntawd, kev haus luam yeeb tuaj yeem txhim kho cov proteinuria hauv cov neeg mob CKD thiab hom 2 mob ntshav qab zib mellitus thiab ua rau qeeb ntawm cov kab mob raum kawg[1-,18]. Ntxiv mus, tus neeg tau txais kev pab lossis tus neeg pub haus luam yeeb ua rau muaj kev tsis lees paub lub sijhawm thiab mob ntev allograft nephropathy, ua rau allograft poob hauv lub raum hloov pauv [19,2o]. Cov teebmeem phem ntawm kev haus luam yeeb (NIC(nicotine)) tau tsom los ntawm kev tshawb fawb hauv nas qauv ntawm s/6 nephrectomy [2al thiab mob ntshav qab zib nephropathy [o]. Hauv kev tshawb fawb tam sim no, peb pom tias NIC(nicotine)aggravated TAC-induced fractional mesangial cheeb tsam thiab TIF. Cov kev hloov pauv pathological no ua rau lub raum ua haujlwm tsis zoo thiab txhawb nqa cov zis protein ntau ntxiv. Raws li cov txiaj ntsig no thiab lwm cov ntawv ceeb toom, peb xav tias kev haus luam yeeb tuaj yeem ua rau lub raum tsis zoo hauv cov neeg tau txais kev hloov pauv uas tau txais TAC-based immunosuppressants.
Inflamation plays lub luag haujlwm tseem ceeb hauv kev hloov pauv ntawm kev mob ntev TACnephrotoxicity vim tias nws ua ntej lub raum caws pliav. Cov kws kho mob muaj zog ntxiv rau hauv cov lus teb rau cov kev mob tshwm sim tuaj yeem nrhiav cov kab mob inflammatory, uas dhau los ua rau cov kab mob profibrotic thiab profibrotic cytokines xws li chemoattractants, adhesion molecules, thiab TGF- 1. Peb tsis ntev los no tau ua pov thawj tias NLRP3-dependent thiab ywj siab inflammasome tau koom nrog hauv pathogenesis ntawm tus mob TAC nephrotoxicity [s]. Peb cov txiaj ntsig tau qhia tias kev tswj hwm NIC(nicotine)rau TAC-kho nas ua kom nthuav dav cov kev qhia ntawm pyroptosis-hais txog cov noob (NLRP3, IL-1 , thiab I-18), proinflammatory mediators MCP-1, thiab profibrotic cytokines TGF- thiab CTGF, ua rau rau ntau dhau ED-1-cov hlwb zoo influx thiab ig-h upregulation; Cov lus teb no qhia txog qhov hnyav ntawm glomerular thiab tubular raug mob. Peb qhov kev tshawb pom tau zoo ib yam nrog cov ntawm Arany et al.[22] thiab Agarwal li al.[23], uas tau qhia txog cov teebmeem ntawm NIC ntawm lub raum mob thiab fibrosis.
Txawm tias NIC(nicotine)-raws li exacerbation ntawm ntev TAC nephrotoxicity nyob rau hauv cov qauv no tej zaum yuav multifactorial, nws muaj feem xyuam rau cov kev cuam tshuam ntawm oxidative kev nyuaj siab. Nws paub zoo tias kev kho mob TAC mob ntev yog cuam tshuam nrog afferent arteriolopathy-txog hypoxia, uas tom qab txuas mus rau oxidative kev nyuaj siab, uas nyob rau hauv lem activates profibrotic TGF- 1 overexpression, ua rau fibrosis. Qhov kev tsim kho no tau txais kev txhawb nqa los ntawm kev soj ntsuam tias cov tshuaj tiv thaiv antioxidant (xws li coenzyme Q10) txo qis TGF- 1 qhia thiab TIF los ntawm kev khaws cia ntawm mitochondrial kev ncaj ncees nyob rau hauv ntev TAC nephrotoxicity 24]. Tsis ntev los no, cov ntaub ntawv pov thawj ntau dhau los ntawm cov kev tshawb fawb hauv vitro qhia tau hais tias muaj kev cuam tshuam ntawm kev raug mob NIC thiab oxidative kev nyuaj siab hauv ntau yam kev raug mob raum [o,25,26. Ntawm no, peb pom tias NIC nce ntshav thiab zis 8-OHdG ntau ntau thiab augmented oxidant protein qhia, thaum nws suppresses antioxidant protein qhia, yog li boosting TAC-induced oxidative kev nyuaj siab nrog rau fibrosis. Tseeb tiag, NIC ua rau lub raum tsis zoo ntawm TAC-kho raum hauv txoj kev tshawb no yuav raug ntaus nqi rau oxidative kev nyuaj siab.
cistanche erectile kawg
Nws tseem muaj peev xwm hais tias ob qho tib si apoptosis (hom I pro-gramed cell tuag) thiab autophagy (hom II programmed cell tuag) koom nrog hauv NIC.(nicotine)- Ua kom nrawm TAC nephrotoxicity. Raws li yav dhau los illustrated, NIC ncaj qha induces podocyte thiab lub raum proximal tubule cell apoptosis [27,28]; nws kuj indirectly induces apoptotic cell tuag ntawm oxidative stress[2g] los yog ua kom TGF- 1[22].NIC(nicotine)kuj tseem tuaj yeem ua rau autophagy hauv pancreatic stellate hlwb Bo], neonatal nas plawv myocytes 31], thiab vascular du leeg hlwb 32]. Yog li, oxidative stress thiab programmed cell tuag muaj kev cuam tshuam. Siv TUNEL kev soj ntsuam thiab electron microscopy, peb tau pom meej tias NIC tau nce tus naj npawb ntawm TUNEL-zoo hlwb hauv tubular epithelial hlwb, interstitial vascular endothelial hlwb, thiab autophagic compartments hauv TAC-kho nas raum. Cov kev hloov morphological no tau nrog los ntawm dysregulation ntawm apoptosis- lossis autophagy-txog cov noob hauv nas raum, ua rau kev tuag ntawm tes. Cov ntaub ntawv pov thawj no qhia tias NIC(nicotine)Nws tus kheej tsis tsuas yog ua rau oxidative kev nyuaj siab thiab programmed cell tuag tab sis kuj txhawb nqa qhov tsis zoo ntawm TAC ntawm lub raum, ua rau lub raum tsis ua haujlwm thiab kev puas tsuaj, raws li yav dhau los tau tshaj tawm hauv cov qauv ntawm streptozotocin (STZ)-induced ntshav qab zib nephropathy [o] thiab CKD ( s/6 nephrectomy) B3].
Tsis tas li ntawd, oxidative stress-originated intracellular organelles xws li mitochondrial dysfunction thiab ER kev nyuaj siab ua lub luag haujlwm tseem ceeb hauv TAC nephrotoxicity integrity, ua rau ER kev nyuaj siab, thiab dysregulate mitochondrially thiab ER kev ntxhov siab-tswj cov noob thiab cov teebmeem yog ob qho tib si nrog kev kho mob. . Yog li, kev tsis zoo ntawm mitochondrial Fitness thiab ER kev ntxhov siab tuaj yeem ua rau muaj txiaj ntsig ntawm NIC(nicotine) ntawm TAC-induced raum raug mob
Peb txoj kev tshawb fawb tau qhia tias NIC(nicotine)ntawm ib koob ntawm 15mg / kg aggravates TAC-vim lub raum raug mob los ntawm oxidative kev nyuaj siab, o, thiab programmed cell tuag, zoo ib yam li yav dhau los kev tshawb fawb [27,37,38]. Txawm li cas los xij, lwm tus tau pom qhov sib txawv qhov kev tshawb pom. Sadis et al.Bg] pom tias NICat ib koob tshuaj ofo.s mg/kg tiv thaiv lub raum los ntawm ischemia/reperfusion raug mob los ntawm txoj kev cholinergic anti-inflammatory. Lwm txoj kev tshawb fawb los ntawm Agarwal li al.[23] qhia tias kev kho qhov ncauj mus ntev nrog NIC(nicotine)(28 lub lis piam) confers renoprotective teebmeem nyob rau hauv ib tug nas qauv ntawm spontaneous proteinuria (Munich-Wistar-Frömter nas). Cov laj thawj rau qhov tsis sib xws hauv lub luag haujlwm ntawm NIC ntawm lub raum tsis paub tab sis yuav nyob ntawm NIC koob tshuaj, lub sijhawm kho tshuaj, lossis tus qauv nas. Yuav tsum muaj kev tshawb fawb ntxiv los daws cov teeb meem no. Txoj kev tshawb no qhia meej meej tias NIC ua rau TAC ua rau lub raum raug mob hauv tus qauv nas ntawm tus mob TAC nephrotoxicity. Kev hnyav ntawm oxidative kev nyuaj siab thiab kev ua haujlwm ntawm tes tuag yuav yog ib qho txheej txheem hauv qab ntawm cov teebmeem ntawm NIC. Peb qhov kev tshawb pom muab kev pom ntau dua rau qhov cuam tshuam ntawm kev haus luam yeeb ntawm cov neeg tau txais kev hloov pauv.
cistamche hauv kev ua haujlwm ntawm lub raum
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