Part Ib Genetic Polymorphisms Ntawm MnSOD Hloov Kho Qhov cuam tshuam ntawm Ib puag ncig Melamine Rau Oxidative Stress Thiab Raum Thaum Ntxov Injury hauv Calcium Urolithiasis Cov Neeg Mob

Abstract

Ib puag ncig melamine raug ua rau muaj kev pheej hmoo ntawm oxidative kev nyuaj siab thiab raug mob raum thaum ntxov. Manganese superoxide dismutase (MnSOD), glutathione peroxidase, thiab catalase tuaj yeem tiv thaiv lub raum tiv thaiv oxidative kev nyuaj siab thiab tswj kev ua haujlwm zoo. Peb tau soj ntsuam seb lawv cov nucleotide polymorphisms (SNPs) puas tuaj yeem hloov kho cov teebmeem ntawm melamine. Tag nrho ntawm 302 tus neeg mob kuaj pom tias muaj calcium urolithiasis tau cuv npe. Txhua tus neeg mob tau muab ib qho kev kuaj zis ib hmos los ntsuas lawv cov qib melamine, cov zis biomarkers ntawm oxidative kev nyuaj siab, thiab lub raum raug mob. Cov txiaj ntsig nruab nrab tau siv los dichotomize qib rau hauv siab thiab qis. Cov ntsiab lus nqa T allele ntawm rs4880 thiab qib melamine siab tau muaj 3.60 npaug ntawm kev pheej hmoo siab ntawm malondialdehyde ntau dua li cov neeg nqa C allele ntawm rs4880 thiab qib melamine qis tom qab hloov kho. Cov ntsiab lus nqa G allele ntawm rs5746136 thiab qib melamine siab tau muaj 1.73 npaug ntawm kev pheej hmoo siab N-Acetyl- -D-glucosaminidase ntau dua li cov neeg nqa A allele ntawm rs5746136 thiab qib melamine tsawg. Hauv kev xaus, SNPs ntawm MnSOD, rs4880, thiab rs5746136, cuam tshuam qhov kev pheej hmoo ntawm oxidative kev nyuaj siab thiab lub raum raug mob, feem, hauv cov neeg mob calcium urolithiasis. Nyob rau hauv cov ntsiab lus ntawm urinary melamine ntau ntau, lawv cov teebmeem ntawm oxidative kev nyuaj siab thiab lub raum tubular raug mob ntxiv ntxiv.

Ntsiab lus

manganese superoxide dismutase; genetic polymorphism; melamine; mob raum; oxidative kev nyuaj siab; calcium urolithiasis.

Nyem qhov no kom tau txais Cistanche extract

Taw qhia

Melamine yog cov khoom siv hluavtaws siv los tsim ntau yam khoom lag luam hauv lub neej txhua hnub nrog rau cov khoom siv hauv tsev, cov txee, ntaub, cov nplaum, thiab cov nplaim hluav taws kub [1,2]. Vim tias nws muaj cov ntsiab lus nitrogen siab, nws tau siv tsis raug rau hauv cov tsiaj pub mis thiab mis nyuj kom dag ntxias cov ntsiab lus protein [1,2]. Qhov tsis zoo ntawm melamine raug cuam tshuam rau thoob ntiaj teb kev saib xyuas tom qab nws qhov tsis txaus ntseeg ntxiv rau cov tsiaj noj, ua rau tuag ntawm ntau txhiab tus tsiaj hauv Asmeskas xyoo 2007, nrog rau cov mis mos, ua rau urolithiasis ntau dua 50,{{6 }} menyuam yaus thiab rau tus neeg tuag hauv Suav teb xyoo 2008 [1,2]. Txog niaj hnub no, melamine tseem muaj nyob hauv peb ib puag ncig. Ntau qhov kev tshawb fawb tau tshawb pom melamine hauv dej, av, qoob loo, cov khoom noj txhua hnub, thiab cov ntaub so ntswg tsiaj [3–5], thiab lwm tus tau kuaj pom nws hauv cov zis feem ntau ntawm ntau tus neeg nyob hauv ntau lub tebchaws [6–9].

Tom qab noj melamine, cuaj caum feem pua ​​​​ntawm nws daim ntawv qub yuav raug tso tawm hauv cov zis hauv 24 teev, yog li lub raum yuav raug melamine ntau dua [1]. Ntxiv rau qhov cuam tshuam ntawm kev siv tshuaj ntau ntau ntawm melamine rau mob nephrotoxicity hauv cov menyuam yaus xyoo 2008, kev siv tshuaj tsawg tsawg rau melamine tau txuas mus rau kev pheej hmoo ntawm lub raum teeb meem, suav nrog kev tsim pob zeb thiab kev ua haujlwm ntawm lub raum tsis zoo rau cov neeg laus [10- 12]. Ib txoj hauv kev uas yuav ua rau cov tshuaj melamine tsawg tsawg tuaj yeem ua rau lub raum raug mob thaum ntxov thiab cov pob zeb tsim yog nws cov txiaj ntsig tsis zoo rau lub raum tubules, raws li tau pom los ntawm ob peb cov tib neeg kev tshawb fawb hauv melamine tableware neeg ua haujlwm [13] thiab cov neeg laus cov neeg mob uas muaj calcium urolithiasis [ 14] ib. Peb kuj tau ua kev tshawb fawb hauv vitro los ntawm kev siv tib neeg lub raum tubular HK{10}} hlwb thiab pom tias melamine tuaj yeem ua rau lub raum puas tsuaj los ntawm kev ua kom muaj zog oxidative [15]. Hauv ob txoj kev tshawb fawb tib neeg tsis ntev los no, peb kuj pom tias raug melamine ua rau cov zis biomarkers ntawm oxidative stress, malondialdehyde (MDA), thiab 8-oxo-20 -deoxyguanosine (8-}OHdG), nrog MDA. Kev sib kho 36–53 feem pua ​​​​ntawm tag nrho cov txiaj ntsig ntawm melamine ntawm biomarker ntawm lub raum tubular raug mob, N-Acetyl- -D-glucosaminidase (NAG) [16]. Cov kev tshawb pom no qhia tau hais tias kev kis tus kab mob tsawg ib puag ncig melamine tuaj yeem ua rau muaj kev ntxhov siab oxidative thiab ntxiv kev pheej hmoo ntawm lub raum thaum ntxov rau tib neeg.

Oxidative stress tshwm sim thaum tiam ntawm pro-oxidants los yog reactive oxygen hom (ROS) tshaj lub endogenous antioxidant muaj peev xwm. Peb ob lub raum tshwj xeeb yog rhiab heev rau oxidative kev nyuaj siab, uas tau xav tias yog ib qho tseem ceeb hauv kev pib, kev loj hlob, thiab kev loj hlob ntawm feem ntau cov kab mob raum [17,18]. Qhov ua rau oxidative kev nyuaj siab nyob rau hauv ob lub raum yuav cuam tshuam nrog kev sib cuam tshuam ntawm cov kab mob kev kho mob thiab ib puag ncig raug rau cov tshuaj xws li melamine [16]. Endogenous antioxidant systems suav nrog manganese superoxide dismutase (MnSOD), glutathione peroxidase (GPX1), thiab catalase (CAT) tau pom los tiv thaiv ob lub raum tiv thaiv oxidative kev nyuaj siab thiab tom qab ntawd pab tswj kev ua haujlwm zoo [18]. MnSOD tuaj yeem decompose tshuaj lom ROS, thiab superoxide anions, mus rau hydrogen peroxide, uas tom qab ntawd hloov mus rau cov dej tsis muaj tshuaj lom thiab oxygen los ntawm GPX1 thiab CAT hauv mitochondria [18]. Ob peb ib leeg-nucleotide polymorphisms (SNPs) ntawm cov noob caj noob ces antioxidant enzyme tau cuam tshuam nrog ntau yam kab mob [19], suav nrog kab mob raum [20–22].

Txij li thaum ib puag ncig toxicant-associated raum puas yuav cuam tshuam los ntawm caj ces yam [23], nws muaj peev xwm hais tias SNPs ntawm antioxidant enzyme noob (xws li, MnSOD, GPX1, CAT) tuaj yeem hloov kho cov teebmeem ntawm ib puag ncig melamine raug rau kev pheej hmoo ntawm oxidative kev nyuaj siab. thiab lub raum tubular raug mob nyob rau hauv tib neeg. Txhawm rau kom paub, peb tau xaiv tsib tus neeg sib tw SNPs ntawm cov tshuaj tiv thaiv kab mob antioxidant (MnSOD: rs4880 thiab rs5746136, GPX1: rs1800668, CAT: rs1001179 thiab rs769217), feem ntau tau txuas rau cov kab mob raum [20-22 ntawm txhua qhov], lawv cov teebmeem thaum ua ke nrog ib puag ncig melamine raug rau ntawm 8-OHdG thiab MDA, ob lub biomarkers ntawm oxidative stress, thiab NAG, biomarker ntawm lub raum tubular raug mob, hauv cov zis.

Cistanche tubulosa thiab Cistanche tshuaj

Cov ntaub ntawv thiab cov txheej txheem

1. Yam

Nyob rau hauv tag nrho, 309 tus neeg mob kuaj pom muaj cov kab mob urinary sab sauv calcium urolithiasis tau cuv npe thaum lub Kaum Ib Hlis 2010 thiab Lub Ib Hlis 2015. Cov ncauj lus kom ntxaws txog kev tsim qauv thiab cov txheej txheem rau lawv suav nrog tau piav qhia yav dhau los [14,16]. Hauv luv luv, txhua tus neeg mob yog los ntawm Kaohsiung Medical University-cov tsev kho mob koom nrog nyob rau sab qab teb sab hnub poob Taiwan. Cov neeg mob tsim nyog yog cov neeg muaj hnub nyoog siab dua lossis sib npaug li 20 xyoo uas tau kuaj pom tias muaj urolithiasis nyob rau hauv cov zis sab sauv los ntawm radiography los yog ultrasonography, thiab cov uas tau muab cov pob zeb kuaj pom tseeb tias muaj calcium Cheebtsam los ntawm infrared spectroscopy tsom xam (Spectrum RX I Fourier Transform. -Infrared System, PerkinElmer, Waltham, MA, USA). Tsis muaj leej twg tuaj koom tau pom los ntawm X-ray kom muaj pob zeb radiolucent los yog los ntawm kev soj ntsuam xyuas kom muaj uric acid lossis cystine pob zeb.

Cov neeg mob raug cais tawm yog tias lawv muaj keeb kwm ntawm kev kis kab mob urinary, mob raws plab, gout, hyperparathyroidism, raum tubular acidosis, lub raum tsis ua haujlwm, lossis mob qog noj ntshav. Txhua tus neeg uas tau noj cov tshuaj vitamin D tsis tu ncua, calcium ntxiv, diuretics, lossis potassium citrate ntau dua ib zaug hauv ib lub lis piam hauv rau lub hlis ua ntej kuaj mob urolithiasis lossis kev xam phaj kuj raug cais tawm. Txoj kev tshawb fawb raws tu qauv tau pom zoo los ntawm Pawg Saib Xyuas Kev Tshawb Fawb ntawm KMUH thiab txhua tus neeg mob tsim nyog tau muab daim ntawv tso cai sau ntawv tso cai. Txoj kev tshawb no tau ua raws li cov lus qhia ntawm STREGA [24] (saib Cov Khoom Siv Ntxiv Ntxiv S1).

2. Sau cov ntaub ntawv kho mob thiab cov qauv tshuaj lom neeg

Thaum nkag, tag nrho cov neeg koom tau muab cov ntshav thiab ib qho chaw ua ntej-vim thaum sawv ntxov cov zis kuaj tom qab hmo ntuj yoo mov thiab ua ntej kev kho mob ntawm urolithiasis rau biochemical thiab genetic analyses. Lawv kuj tau teb cov lus nug uas tsim nyog los sau lawv cov ntaub ntawv pej xeem, keeb kwm kev kho mob, thiab kev siv yeeb tshuaj (luam yeeb, cawv, thiab betel quid) [14,16]. Cov neeg koom nrog raug txhais tias yog cov neeg haus luam yeeb, haus cawv, lossis cov neeg haus cawv yog tias lawv tau haus luam yeeb ntau dua lossis sib npaug li 10 luam yeeb hauv ib lub lis piam, tau haus cawv ntau dua lossis sib npaug li 1 zaug hauv ib lub lis piam, lossis tau zom ntau dua lossis sib npaug li 7 betel quids hauv ib lub lis piam, feem, tsawg kawg yog rau lub hlis. Cov neeg siv tam sim no yog cov uas tseem xyaum cov cwj pwm saum toj no hauv ib xyoos ua ntej kuaj mob urolithiasis lossis kev xam phaj [11,25].

Cov ntaub ntawv kho mob, suav nrog qhov chaw pob zeb, pob zeb naj npawb, pob zeb txoj kab uas hla, thiab cov ntu pob zeb, kuj tau sau los ntawm daim ntawv nug thiab tshuaj xyuas ntxiv siv cov neeg mob cov kab kos kho mob los ntawm ib tus kws kho mob urologist (C.-CL) uas tsis paub txog qhov cuam tshuam ntawm kev txaus siab, suav nrog melamine thiab biomarkers ntawm oxidative kev nyuaj siab (8-OHdG thiab MDA) thiab raum tubular raug mob (NAG) nyob rau hauv cov zis thiab genotyping ntawm antioxidant enzyme noob.

Cistanche capsules

3. Kev soj ntsuam ntawm Melamine, Biomarkers ntawm Oxidative Stress (MDA thiab 8-OHdG), thiab Lub raum Tubular Injury (NAG) hauv cov zis

Urinary melamine raug ntsuas los ntawm isotopic kua chromatography-tandem mass spectrometry method (LC-MS/MS) (API40{{20}}0Q, Applied Biosystems/MDS SCIEX , Concord, Vaughan, ON, Canada) [13]. Urinary MDA tau ntsuas los ntawm kev siv cov kua dej chromatography nrog cov fluorescence (HPLC-FL) nrhiav pom nyob rau hauv kab rov qab-theem (Luna C18, 250 × 4.6 nm) [26]. Urinary 8-OHdG raug ntsuas los ntawm kev siv txoj kev siv tau rau hauv online solid-phase extraction (SPE) LC-MS/MS [27]. Cov txheej txheem ntxaws tau piav qhia yav dhau los [14,16]. Cov kev txwv ntawm kev kuaj pom (LOD) rau urinary melamine thiab biomarkers ntawm oxidative kev nyuaj siab yog 0.4 ng / ml rau melamine, 0.02 µmol / L rau MDA, thiab 0.01 ng / mL rau 8-OHdG. Txhua qhov kev ntsuas zis ntawm MDA thiab 8-OHdG tau kuaj pom. Hauv qhov sib piv, 31 (10.0 feem pua) ntawm 309 urinary melamine ntsuas tau qis dua LOD thiab raug hloov ua LOD/√ 2.

Urinary NAG raug ntsuas siv NAG cov khoom siv tshuaj ntsuam (Diazyme Laboratory, Poway, CA, USA) [13,14]. Tag nrho cov kev ntsuas urinary NAG tau kuaj pom. Cov zis creatinine tau soj ntsuam los ntawm spectrophotometric (U-2000; Hitachi, Tokyo, Nyiv) teeb tsa ntawm lub wavelength ntawm 520 nm los ntsuas cov tshuaj tiv thaiv creatinine-picrate [14]. Kev ntsuas ntawm txhua qhov kev ntsuas biochemical saum toj no tau ua los ntawm ob tus kws kuaj mob sib txawv uas tsis pom kev rau ib leeg qhov kev tshawb pom, kev tsim qauv, thiab cov ntaub ntawv koom nrog.

4. Genotyping ntawm tsib SNPs

DNA tau muab rho tawm los ntawm cov ntshav peripheral tag nrho siv Puregene DNA Isolation Kit (Gentra Systems Inc., Minneapolis, MN, USA). Lub tsib SNPs (MnSOD-rs4880, MnSODrs5746136, GPX1-rs1800668, CAT-rs1001179, thiab CAT-rs769217) tau soj ntsuam siv qhov kev ntsuam xyuas-on-demand SNP genotypingMan 5 cov khoom siv rau tag nrho cov txheej txheem , Foster City, CA, USA). Luv luv, SNP amplification assays suav nrog 10 ng ntawm cov qauv DNA hauv 25 µL ntawm cov tshuaj tiv thaiv muaj 12.5 µL ntawm 2 × TaqMan®Universal PCR Mix (Applied Biosystems), thaum 1.25 µL ntawm pre-tsim assay reagent los ntawm SNP genotyping khoom ( Biosystems) muaj ob primers. Ob qhov kev sojntsuam MCB-Taqman tau ua raws li cov lus qhia ntawm cov chaw tsim khoom. Polymerase chain reactions (PCRs) tau ua los ntawm ABI Prism 7500 Sequence Detection System (Applied Biosystems) [28,29]. Cov genotypes no tau lees paub los ntawm kev sib txuas ncaj qha tom qab tag nrho-scale genotyping. Randomly, ~ 10 feem pua ​​​​ntawm cov qauv kev tshawb fawb (30 kis) tau rov ua dua rau kev tswj xyuas kom zoo, nrog rau cov txiaj ntsig tau pom 100 feem pua ​​​​qhov tseeb.

Cov txiaj ntsig ntawm Cistanche

5. Kev txheeb xyuas qhov tseeb

Cov ntaub ntawv ntau tau raug nthuav tawm raws li txhais tau tias ± tus qauv sib txawv (SD) lossis nruab nrab nrog qhov sib txawv ntawm qhov sib txawv (IQR), thiab cov ntaub ntawv categorical tau nthuav tawm ua tus lej (n) thiab feem pua. Hardy-Weinberg equilibrium rau kev faib tawm ntawm genotypes tau kuaj xyuas siv qhov ntsuas chi-square.

Cov qib melamine hauv cov zis thiab cov zis biomarkers (MDA, 8-OHdG, NAG) raug kho los ntawm urinary creatinine qhov tseem ceeb ua ntej kev tshuaj ntsuam ntxiv. Tom qab kho, urinary biomarkers ntawm oxidative kev nyuaj siab (MDA thiab 8-OHdG) thiab raum tubular raug mob (NAG) tau dichotomized rau hauv siab lossis qis siv lawv qhov nruab nrab [14,16]. Cov qauv yooj yim logistic regression yog thawj zaug siv los ntsuas cov kev sib koom ua ke ntawm cov genotypes ntawm antioxidant enzymes thiab cov zis biomarkers ntawm oxidative kev nyuaj siab thiab lub raum tubular raug mob. Yog tias muaj kev sib raug zoo tseem ceeb hauv qhov kev tshuaj ntsuam thawj zaug, qhov sib xyaw ua ke ntawm cov genotypes ntawm cov tshuaj antioxidant enzymes thiab cov urinary melamine theem dichotomized los ntawm qhov nruab nrab qhov tseem ceeb tau sim ntxiv los ntawm ntau qhov kev ntsuam xyuas kev rov qab los tom qab hloov kho covariates, xws li hnub nyoog, poj niam txiv neej, BMI, kev kawm. qib, tus cwj pwm ntawm tus kheej, tus lej pob zeb, pob zeb loj, qhov chaw pob zeb, thiab kev sib txuam. Tag nrho cov kev txheeb xyuas kev txheeb xyuas tau ua tiav siv SAS cov ntaub ntawv pov thawj pob. Tag nrho p-tus nqi yog ob sab thiab suav tias tseem ceeb yog tias<0.05.

6. Kev Ntsuas Kev Ntsuas

Txhawm rau tshuaj xyuas qhov ua tau zoo ntawm peb qhov kev tshawb pom, peb tau ua qhov kev soj ntsuam rhiab heev los sib piv cov txiaj ntsig thaum urinary melamine qib tau muab faib ua tertiles. Tsis tas li ntawd, peb kuj sib piv cov kev tshawb pom uas siv ib txoj kev tshiab ntawm covariate-kho standardization ntxiv rau creatinine hloov kho kom cov zis concentration thiab nyuaj confounding lug [14,30].

Cov ntaub ntawv

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Chia-Chu Liu 1,2,3,4, Chia-Fang Wu 1,5, Yung-Chin Lee 2,3,6, Tsung-Yi Huang 2, Shih-Ting Huang 1,7, Hsun-Shuan Wang 6, Jhen-Hao Jhan 6, Shu-Pin Huang 2,3, Ching-Chia Li 2,3, Yung-Shun Juan 2,3, Tusty-Jiuan Hsieh 1,7, Yi-Chun Tsai 1,8,9, Chu- Chih Chen 1,10 thiab Ming-Tsang Wu 1,11,12,13,

1 Lub Chaw Tshawb Fawb Txog Kev Noj Qab Haus Huv Ib puag ncig, Kaohsiung Medical University, Kaohsiung City 807, Taiwan; ccliu0204@gmail.com (C.-CL); cfwu27@nuu.edu.tw (C.-FW); u107800006@kmu.edu.tw (S.-TH); hsiehjun@kmu.edu.tw (T.-JH); 920254@kmuh.org.tw (Y.-CT); ccchen@nhri.edu.tw (C.-CC)

2 Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City 807, Taiwan; 890197@kmuh.org.tw (Y.-CL); 970417@kmuh.org.tw (T.-YH); shpihu@kmu.edu.tw (S.-PH); 850144@kmuh.org.tw (C.-CL); 840066@kmuh.org.tw (Y.-SJ)

3 Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City 807, Taiwan

4 Department of Urology, Pingtung Tsev Kho Mob, Ministry of Health thiab Welfare, Pingtung City 900, Taiwan

5 International Master Program of Translational Medicine, National United University, Miaoli 360, Taiwan

6 Department of Urology, Kaohsiung Municipal Siaogang Tsev Kho Mob, Kaohsiung City 812, Taiwan; 940199@kmuh.org.tw (H.-SW); 1030398@kmuh.org.tw (J.-HJ)

7 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City 807, Taiwan

8 Department of Internal Medicine, Division of Nephrology and General Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City 807, Taiwan

9 Department of Internal Medicine, Tsev Kawm Ntawv Tshuaj, Tsev Kawm Qib Siab Tshuaj, Kaohsiung Medical University, Kaohsiung City 807, Taiwan

10 Division of Biostatistics thiab Bioinformatics, Lub koom haum ntawm Population Health Sciences, National Health Research Institutes, Miaoli 350, Taiwan

11 Environmental and Occupational Medicine and Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung City 807, Taiwan

12 Department of Family Medicine, Kaohsiung Medical University Tsev Kho Mob, Kaohsiung Medical University, Kaohsiung City 807, Taiwan

13 Department of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung City 807, Taiwan