Kev Siv Tshuaj Kho Mob MPA nyob rau theem pib, nruab nrab thiab lig tom qab hloov raum

Cov tshuaj Mycophenolic acid (MPA) yog ib qho tseem ceeb ntawm kev tiv thaiv kab mob hauv paus thiab ib qho ntawm thawj cov tshuaj tiv thaiv kab mob rau cov neeg tau txais kev hloov hauv lub raum. Txij li thaum Tebchaws Meskas tau ua tiav lub ntiaj teb thawj lub raum hloov pauv hauv xyoo 1954, nws tau ntsib 70 xyoo ntawm kev txhim kho. Tau ntev, ntau qhov kev tshawb fawb thaj av tau tsim lub hauv paus kev tiv thaiv kab mob ntawm mycophenolate mofetil (MMF) [1]. Yuav ua li cas tus qauv siv cov tshuaj MPA tom qab hloov lub raum yog ib qho ntawm cov ntsiab lus kub ntawm kev txhawj xeeb. Nyob rau hauv qhov teeb meem no ntawm "loj tham", xibfwb Chen Gang los ntawm Tongji Tsev Kho Mob Affiliated nrog Huazhong University of Science thiab Technology tshwj xeeb yog caw xibfwb Chen Gang los ntawm thaum ntxov, nruab nrab, thiab lig theem ntawm lub raum hloov. Daim ntawv thov thiab kev siv tshuaj MPA hauv cov neeg mob lub raum hloov pauv tau piav qhia meej rau cov txiaj ntsig ntawm cov neeg nyeem.

Nyem rau Cistanche rau mob raum

Kev siv tshuaj MPA thaum ntxov tom qab hloov lub raum

MMF + cyclosporine los yog tacrolimus (Tac) ± glucocorticoids yeej ib txwm yog thawj kab hauv paus tshuaj tom qab hloov lub raum, thiab tau txais kev pom zoo los ntawm cov lus qhia hauv tsev thiab txawv teb chaws xws li KDIGO Cov Lus Qhia, Cov Lus Qhia European, thiab "Clinical Application Code of Immunosuppressants for Organ Kev hloov pauv hauv Suav teb" (2019 tsab) tau pom zoo pom zoo. Xib fwb Chen tau hais tias hauv kev kho mob, Tac + MMF ± glucocorticoids yog cov tshuaj tiv thaiv kab mob tiv thaiv kab mob tam sim no, suav txog ntau dua 90% [2,3].

Yuav siv cov tshuaj MPA li cas thaum ntxov tom qab hloov lub raum? "Kev pom zoo ntawm Cov Kws Paub Txog Kev Siv Tshuaj Mycophenolic Acid hauv Suav Daim Siab thiab Raum Hloov Cov Neeg Tau Txais (2023 tsab)" (tom qab no hu ua tus tshiab version ntawm kev pom zoo) pom zoo tias qhov ncauj MPA tshuaj, MMF thiab Mai yuav tsum pib 12 teev ua ntej hloov lub raum los yog hauv 24 teev tom qab hloov lub raum. Cov koob tshuaj pib ntawm cocophenolate sodium enteric-coated ntsiav tshuaj (EC-MPS) yog 0.75 mus rau 1.0 g thiab 540 txog 720 mg txhua zaus, raws li, ib zaug txhua 12 teev [4]. Cov koob tshuaj pib tuaj yeem txiav txim siab raws li tus neeg sib txawv ntawm cov neeg tau txais txiaj ntsig, xws li lub cev qhov hnyav lossis kev tiv thaiv kab mob, thiab cov koob tshuaj tuaj yeem hloov kho raws li cov tsos mob tshwm sim los yog MPA-AUC los xyuas kom meej qhov tshwm sim ntxov thiab txaus rau MPA.

Xib fwb Chen tau hais ntxiv tias qhov ntau npaum li cas ntawm MPA tshuaj sib txawv ntawm ntau pawg neeg. Lub cev hnyav, thaj chaw ntawm lub cev, thiab cov noob caj noob ces ntawm cov neeg Esxias txawv ntawm cov neeg nyob sab Europe thiab Asmeskas, uas ua rau muaj qhov sib txawv ntawm kev kam rau tshuaj. Cov kev tshawb fawb tau pom tias qhov koob tshuaj txhua hnub ntawm MMF haum rau cov neeg Esxias yuav tsum raug txo los ntawm 20% mus rau 46% piv nrog cov neeg Caucasians lossis African Asmeskas [5]. Yog li ntawd, koob tshuaj pib thiab hloov koob tshuaj MMF thiab EC-MPS yuav tsum yog tus kheej [4].

What are the clinical benefits of early and sufficient exposure to MPA drugs? Professor Chen gave examples of domestic and foreign studies. The French APOMYGRE study monitored the MPA-AUC of 137 kidney transplant recipients. They followed up for 12 months and adjusted the MPA-AUC of the concentration control group (CC group) to 40mg·h. /L or above, compared with the fixed-dose group (FD group), the results found that MPA-AUC>40mg·h/L, qhov tshwm sim ntawm kev tsis lees paub mob hnyav (AR) hauv 12 lub hlis tau txo qis [6]. Cov kev tshawb fawb hauv tsev kuj pom tau hais tias lub raum interstitial fibrosis thiab juxtaglomerular fibrosis cov qhab nia ntawm cov neeg mob nyob rau hauv cov pa MMF pawg (MMF koob ntau dua lossis sib npaug li 1.5g) tau qis dua li cov neeg nyob hauv pawg tsawg (0.{ {7}}.

Tsis tas li ntawd, xibfwb Chen tau taw qhia tias kev ncua sij hawm rov qab los ntawm kev ua haujlwm graft (DGF) tom qab hloov lub raum yog qhov muaj feem cuam tshuam rau kev muaj sia nyob ntawm graft thiab tseem tuaj yeem cuam tshuam rau MPA. Qhov kev pom zoo tshiab pom zoo kom kho qhov ntau npaum li cas thiab ua tib zoo saib xyuas cov tshuaj tiv thaiv tsis zoo raws li kev kho mob tshwm sim lossis MPA-AUC [4].

Kev siv cov tshuaj MPA hauv nruab nrab thiab lig theem tom qab hloov lub raum

Nws paub zoo tias cov kab mob metabolic yog qhov muaj feem cuam tshuam rau cov kab mob plawv, thiab qhov tshwm sim ntawm metabolic syndrome tom qab hloov lub raum yog 25.7% rau 34.6% [8]. Cov ntawv tshiab ntawm qhov kev pom zoo tau taw qhia tias MPA cov tshuaj tsis muaj qhov cuam tshuam loj rau cov kab mob metabolic thiab tsis muaj qhov pom tseeb nephrotoxicity. Cov koob tshuaj niaj hnub tau pom zoo ntawm MMF thiab EC-MPS yog 1.0~ 1.5g thiab 720~1080mg raws li, uas tuaj yeem hloov kho raws li kev kho mob tshwm sim lossis kev pheej hmoo ntawm kev tiv thaiv kab mob [ 4]. Thaum MPA cov tshuaj tsis ua rau muaj kev pheej hmoo ntawm cov kab mob metabolic, cov koob tshuaj ntawm MMF tuaj yeem txo tus nqi ntawm lub raum tsis ua haujlwm. Cov kev tshawb fawb hauv tsev tau pom tias qhov kev hloov pauv hauv lub raum poob qis hauv cov koob tshuaj MMF (1.5g) pawg tau qis dua li ntawm pawg qis (0.5 ~ 1.0g) thiab ultra-low-dose (<0.5g) group [7].

Xib Fwb Chen tau ceeb toom cov kws kho mob tias qhov tseem ceeb ntawm kev muaj sia nyob mus ntev ntawm kev hloov lub raum yog cuam tshuam nrog kev tsim cov tshuaj tiv thaiv tshwj xeeb (DSA). MPA cov tshuaj muaj peev xwm inhibit qhov ua kom thiab proliferation ntawm lymphocytes, yog li inhibiting zus tau tej cov DSA [9,10]. Cov kev tshawb fawb tau pom tias kev siv MMF tam sim ntawd tom qab kev phais tuaj yeem txo qhov feem pua ​​​​ntawm cov neeg tau txais kev hloov hauv lub raum uas tsim DSA rau 8.3% [11]. Lwm cov kev tshawb fawb tau pom tias MPA concentration<1.3 mg/L after transplantation is related to the formation of DSA [12]. Therefore, the new consensus recommends that adequate immunosuppression is crucial for the prevention and treatment of antibody-mediated rejection (AMR). MPA drugs inhibit the production of antibodies including DSA by inhibiting B cell proliferation. Therefore, sufficient MPA exposure is necessary, and it is recommended to pay attention to the immune status and tolerance of the recipient [4].

Tsis tas li ntawd, qhov tshwm sim ntawm calcineurin inhibitor (CNI) nephrotoxicity nyob rau hauv cov neeg tau txais kev hloov hauv lub raum tuaj yeem ncav cuag 24% hauv 1 xyoos tom qab kev phais thiab nce ntxiv nrog lub sijhawm [13,14]. Cov kev tshawb fawb tau pom tias kev nce koob tshuaj MPA tuaj yeem txhim kho qhov kwv yees glomerular filtration rate (eGFR) thiab txo qhov kev pheej hmoo ntawm nephrotoxicity [15,16]. Yog li ntawd, tus tshiab version ntawm qhov kev pom zoo pom zoo tias thaum mob raum allograft raug mob raug txiav txim los ntawm tus mob CNI nephrotoxicity, nws raug nquahu kom tsim nyog nce cov tshuaj uas tsis yog-nephrotoxic xws li MPA / mammalian lub hom phiaj ntawm rapamycin inhibitor (mTORi) thaum txo cov koob tshuaj ntawm CNI. tiv thaiv kev tsis lees paub [4]. Xibfwb Chen kuj tau muab piv txwv txog kev kawm yav tom ntej, txoj kev kawm TranCept. Cov txiaj ntsig tau pom tias ntawm cov neeg tau txais lub raum tsis zoo tom qab hloov lub raum, MMF Ntau dua lossis sib npaug rau 1.0 g / d tau cuam tshuam nrog eGFR cov txiaj ntsig zoo dua. Kev noj ntau npaum MMF (ze li 2.0 g/d) ua ke nrog cov koob tshuaj qis CNI tuaj yeem txhim kho lub raum ua haujlwm tau zoo [17].

Kev siv cov tshuaj MPA hauv cov neeg mob raum hloov cov neeg tau txais kev pab

Xib fwb Chen tau hais tias tam sim no muaj cov pov thawj kev kho mob tsawg heev ntawm cov tshuaj MPA hauv Suav cov neeg mob raum hloov pauv, thiab cov kev tshawb fawb yav dhau los feem ntau yog siv cov koob tshuaj tas li lossis kho cov koob tshuaj raws li AUC. Tus tshiab version ntawm qhov kev pom zoo pom zoo kom kho cov koob tshuaj raws li tus neeg tau txais kev pab lub hnub nyoog, thaj tsam ntawm lub cev, qhov hnyav, plasma concentration ntawm MPA cov tshuaj, thiab cov neeg tau txais kev pom zoo, thiab xyuam xim rau cov kev hloov pauv hauv cov lej lymphocyte [4]. Cov lus qhia MMF hauv tsev qhia: tias koob tshuaj pom zoo rau cov menyuam yaus tom qab hloov lub raum yog qhov ncauj MMF 600mg / m2 txhua zaus, ob zaug ib hnub (ntau tshaj 1g txhua zaus, ob zaug hauv ib hnub) [18].

Thaum kawg, xibfwb Chen tau sau cov ntsiab lus luv luv ntawm cov ntsiab lus tseem ceeb:

1. Triple immunosuppressive regimen ntawm MPA ua ke nrog CNI thiab glucocorticoids yog ib qho kev siv thawj zaug thiab kev saib xyuas kev kho mob rau cov neeg tau txais kev hloov hauv lub raum thiab tau pom zoo los ntawm ntau cov lus qhia.

2. Cov tshuaj MPA tsis muaj kev cuam tshuam rau cov kab mob metabolic thiab tsis pom tseeb nephrotoxicity. Cov tshuaj tiv thaiv peb npaug ntawm cov tshuaj MPA txaus ua ke nrog cov tshuaj tsawg tsawg CNI thiab glucocorticoids tuaj yeem ua kom muaj txiaj ntsig zoo thiab kev nyab xeeb.

3. Thaum mob graft raum raug mob los ntawm kev mob CNI nephrotoxicity, nws raug nquahu kom tsim nyog nce cov tshuaj uas tsis yog-nephrotoxic (MPA/mTORi) thaum txo cov tshuaj CNI kom tiv thaiv kev tsis lees paub.

4. Cov tshuaj MPA ntawm qhov ncauj yuav tsum tau pib 12 teev ua ntej hloov lub raum lossis hauv 24 teev tom qab hloov lub raum. Qhov pom zoo pib koob tshuaj MMF thiab EC-MPS yog 0.75-1.0g thiab 540-720mg txhua zaus, raws li, ib zaug txhua 12 teev.

Cistanche kho mob raum li cas?

Cistancheyog ib hom tshuaj suav tshuaj ntsuab siv rau ntau pua xyoo los kho ntau yam mob, suav nrograumkab mob. Nws yog muab los ntawm qhuav stems ntawmCistanchedeserticola, ib tsob nroj nyob rau hauv cov suab puam ntawm Tuam Tshoj thiab Mongolia. Lub ntsiab active Cheebtsam ntawm cistanche yogphenylethanoidglycosides, echinacoside cov tshuaj, thiabacteoside, uas tau pom tias muaj txiaj ntsig zoo rauraumnoj qab haus huv.

Kab mob raum, tseem hu ua kab mob raum, hais txog ib yam mob uas lub raum ua haujlwm tsis zoo. Qhov no tuaj yeem ua rau muaj cov khoom pov tseg thiab cov co toxins hauv lub cev, ua rau muaj ntau yam tsos mob thiab teeb meem. Cistanche tuaj yeem pab kho mob raum ase los ntawm ntau lub tshuab.

Ua ntej, cistanche tau pom tias muaj cov nyhuv diuretic, txhais tau tias nws tuaj yeem ua rau cov zis ntau ntxiv thiab pab tshem tawm cov khoom pov tseg ntawm lub cev. Qhov no tuaj yeem pab txo lub nra ntawm lub raum thiab tiv thaiv kev tsim cov co toxins. Los ntawm kev txhawb nqa diuresis, cistanche kuj tseem tuaj yeem pab txo qis ntshav siab, ib qho teeb meem ntawm cov kab mob raum.

Ntxiv mus, cistanche tau pom tias muaj cov teebmeem antioxidant. Kev ntxhov siab oxidative, tshwm sim los ntawm qhov tsis sib xws ntawm kev tsim cov dawb radicals thiab lub cev tiv thaiv antioxidant, ua lub luag haujlwm tseem ceeb hauv kev mob raum. ies pab neutralize dawb radicals thiab txo Oxidative kev nyuaj siab, yog li tiv thaiv lub raum los ntawm kev puas tsuaj. Cov phenylethanoid glycosides pom hauv cistanche tau tshwj xeeb hauv kev tshem tawm cov dawb radicals thiab inhibiting lipid peroxidation.

Tsis tas li ntawd, cistanche tau pom tias muaj cov nyhuv anti-inflammatory. Kev mob yog lwm yam tseem ceeb hauv kev loj hlob thiab kev loj hlob ntawm cov kab mob raum. Cistanche's anti-inflammatory zog pab txo cov zus tau tej cov pro-inflammatory cytokines thiab inhibit qhov ua kom o yuav tsum tau txoj kev, yog li alleviating o nyob rau hauv lub raum.

Tsis tas li ntawd, cistanche tau pom tias muaj cov teebmeem immunomodulatory. Hauv kab mob raum, lub cev tiv thaiv kab mob tuaj yeem ua rau tsis zoo, ua rau muaj kev mob ntau dhau thiab cov ntaub so ntswg puas. Cistanche pab tswj lub cev tiv thaiv kab mob los ntawm kev hloov kho kev tsim khoom thiab kev ua haujlwm ntawm lub cev tiv thaiv kab mob, xws li T hlwb thiab macrophages. Txoj cai tiv thaiv kab mob no pab txo qhov mob thiab tiv thaiv kev puas tsuaj ntxiv rau lub raum.

Ntxiv mus, cistanche tau pom los txhim kho lub raum kev ua haujlwm los ntawm kev txhawb nqa kev tsim kho ntawm lub raum hlab nrog cov hlwb. Lub raum tubular epithelial hlwb ua lub luag haujlwm tseem ceeb hauv kev pom thiab rov nqus cov khoom pov tseg thiab electrolytes. Hauv kab mob raum, cov hlwb no tuaj yeem raug puas tsuaj, ua rau lub raum ua haujlwm puas. Cistanche lub peev xwm los txhawb kev tsim kho ntawm cov hlwb no pab kho lub raum kom zoo thiab txhim kho lub raum tag nrho.

Ntxiv nrog rau cov kev cuam tshuam ncaj qha rau lub raum, cistanche tau pom tias muaj txiaj ntsig zoo rau lwm yam kabmob thiab lub cev hauv lub cev. Txoj hauv kev zoo rau kev noj qab haus huv no tseem ceeb tshwj xeeb hauv cov kab mob raum, vim tias tus mob feem ntau cuam tshuam rau ntau lub cev thiab lub cev. che tau pom tias muaj kev tiv thaiv rau lub siab, lub plawv, thiab cov hlab ntsha, uas feem ntau cuam tshuam los ntawm kab mob raum. Los ntawm kev txhawb nqa kev noj qab haus huv ntawm cov kabmob no, cistanche pab txhim kho lub raum tag nrho thiab tiv thaiv kev mob ntxiv.

Hauv kev xaus, cistanche yog cov tshuaj suav tshuaj ntsuab siv rau ntau pua xyoo los kho mob raum. Nws cov active Cheebtsam muaj diuretic, antioxidant, anti-inflammatory, immunomodulatory, thiab regenerative teebmeem, uas pab txhim kho lub raum ua haujlwm thiab tiv thaiv ob lub raum los ntawm kev puas tsuaj ntxiv. , cistanche muaj txiaj ntsig zoo rau lwm yam kabmob thiab lub cev, ua rau nws txoj hauv kev zoo rau kev kho mob raum.