Tshooj 2 Repurposing Tshuaj Rau Cov Kab Mob Loj Tshaj Plaws: Pentoxifylline, Tshuaj Laus Thiab Ib Lub Sijhawm Tshiab Rau Mob Ntshav Qab Zib Raum

PENTOXIFYLLINE hauv DKD

Ib tug qub phooj ywg tshiab

Pentoxifylline [3,7-dimethyl-1-(5-oxohexyl)-3,7-dihydro-1Hpurine-2,{{8} }}dione] yog ib qho kev cog lus los tiv thaiv methylxanthine derivative nrog hemorheological ua. Pentoxifylline tau pom zoo los ntawm Teb Chaws Asmeskas FDA rau kev kho mob ntawm kev sib cuam tshuam claudication tshwm sim los ntawm kab mob peripheral vascular ＞ 30 xyoo dhau los [87–89]. Cov tshuaj no txo ​​cov ntshav viscosity, erythrocyte aggregation, erythrocyte rigidity, thiab platelet aggregation. Kev txhim kho hauv cov ntshav liab hloov tau yooj yim thiab deformability ua rau cov ntshav khiav tau zoo [89, 90]. Lub pharmacological zog ntawm pentoxifylline tau nquag rov mus xyuas, thiab cov pov thawj tsis ntev los no qhia tau tias muaj lwm yam txiaj ntsig zoo ntawm cov tshuaj qub no [91]. Yog li, qhov repurposing ntawm pentoxifylline tau pom zoo rau kev kho mob hlwb ischemia, tsis-alcoholic fatty siab kab mob, thiab khaws cia skeletal leeg muaj nuj nqi [90].

Nyem qhov no kom tau txaiscov txiaj ntsig ntawm Cistanche

Cov khoom hemorheological thiab lawv lub peev xwm los txo qis intraglomerular siab ua rau muaj kev txaus siab thaum ntxov hauv pentoxifylline raws li tus neeg sawv cev kho mob raum kab mob. Xyoo 1982, Blagosklonnaia et al. [92] nthuav tawm thawj cov pov thawj kho mob ntawm lub raum tiv thaiv cov teebmeem ntawm pentoxifylline. Cov neeg mob ntshav qab zib tau kho nrog 300 mg / hnub ntawm pentoxifylline rau 3 lub lis piam txhim kho eGFR thiab txo cov proteinuria. Qhov ua tau daim ntawv thov pentoxifylline rau kev tiv thaiv raum hauv DKD tsis ntev los no tau rov ua dua tshiab raws li cov kev tshawb fawb pom tias pentoxifylline los tiv thaiv kev mob, tiv thaiv kev loj hlob thiab tiv thaiv fibrotic cuam tshuam [93, 94] (Table 1).

Ib qho ntawm tsib qhov kev sim tshuaj qhib-label tau ua nyob nruab nrab ntawm 1999 thiab 2006 tsom rau qhov muaj peev xwm tiv thaiv lub raum ntawm pentoxifylline hauv DKD (Table 1). Ua ntej, Navarro et al. [95] tau tshaj tawm txog 42.2 thiab 59.3 feem pua ​​​​txo qis hauv cov qog nqaij hlav necrosis (TNF) thiab qib proteinuria, feem, hauv ib pawg me ntawm cov neeg mob DM thiab qib siab CKD nyob rau hauv kev kho mob pentoxifylline (400 mg / hnub; 6 lub hlis) thaum piv nrog ib pawg tswj. Tom qab, ob lub npe qhib RCTs ua los ntawm Aminorroaya li al. [96] thiab Rodríguez-Morán et al. [97] kuj tau tshaj tawm txog kev txo qis hauv proteinuria hauv cov neeg mob uas tsis muaj ntshav siab hom 2 DM nrog microalbuminuria piv nrog cov ua tiav nrog kev kho ACEI (captopril) tom qab kev tswj hwm ntawm 400 mg pentoxifylline peb zaug ib hnub (tid) rau 2 (40 feem pua ​​​​hauv pentoxifylline. -pab pawg thiab 38.5 feem pua ​​​​hauv captopril-group) thiab 6 lub hlis (77.2 feem pua ​​​​hauv pentoxifylline-pawg thiab 76.6 feem pua ​​​​hauv captopril pawg), feem. Hauv kev sib tw tom ntej, qhib-label sim, Navarro li al. [98] pom qhov txo qis hauv cov proteinuria ntawm 11.2 feem pua ​​​​hauv cov neeg mob ARB-kho DM uas kuj tau txais 1200 mg / hnub pentoxifylline rau 4 lub hlis; xws li cov neeg mob tau txais pentoxifylline. Kev kho Pentoxifylline kuj tseem txo qis hauv cov ntshav thiab cov zis ntawm TNF, tsis muaj qhov hloov pauv tseem ceeb hauv cov neeg mob tshwj xeeb hauv kev kho nrog ARB. Cov nyhuv antiproteinuric ntawm pentoxifylline cuam tshuam nrog kev txo qis hauv cov zis TNF qib [98]. Thaum kawg, tom qab RCT los ntawm Rodríguez-Morán li al. [99] nyuam qhuav tshaj tawm txog qhov txo qis ntawm cov qib siab thiab qis molecular hnyav urinary protein excretion (73.8 thiab 86.4 feem pua ​​​​qis, feem) hauv cov neeg mob uas tsis yog-hypertensive microalbuminuric hom 2 DM kho nrog 400 mg pentoxifylline ( tid rau 16 lub lis piam) tsis tau txais ACEi lossis ARB kho. Ib qho RCT luam tawm los ntawm Badri li al. [100] pom 56 feem pua ​​​​ntawm cov proteinuria txo qis hauv ib pawg me me ntawm cov neeg mob uas tsis yog mob ntshav qab zib mellitus nrog glomerulonephritis nrog kev kho ntxiv ntawm pentoxifylline rau keeb kwm RAS thaiv tsis muaj kev cuam tshuam eGFR. Lwm qhov kev sim tshuaj nrog cov qauv kev tshawb fawb sib txawv, kev siv tshuaj ntau npaum li cas, thiab lub sijhawm rov qab los, kuj tau tshuaj xyuas lub raum tiv thaiv cov teebmeem ntawm pentoxifylline nrog cov txiaj ntsig tsis txaus ntseeg. Ib qho qhib-label tswj kev sim tshuaj xyuas los ntawm Diskin li al. [101] tsis pom muaj cov nyhuv antiproteinuric ntxiv ntawm pentoxifylline hauv cov neeg mob ntshav qab zib glomerulosclerosis nrog keeb kwm ntawm ACEI thiab ARB kev kho mob tom qab 1 xyoos tom qab. Cov kev txhawj xeeb tseem ceeb ntawm txoj kev tshawb fawb no yog nws qhov tsis yog-randomized tsim, cov neeg koom nrog tsawg (14 tus neeg mob), thiab kev siv dual RAS thaiv, uas muaj kev txhawj xeeb txog kev nyab xeeb tseem ceeb [25, 112]. Hauv ob qhov muag tsis pom RCT, Perkins thiab al. [102] kuj pom tias tsis muaj qhov sib txawv ntawm cov proteinuria hauv 40 DKD cov neeg mob uas mob me mus rau nruab nrab CKD tom qab 1 xyoos ntawm kev kho pentoxifylline ntxiv rau RAS blockade. Txawm li cas los xij, lawv tau pom tias qhov kev ua haujlwm ntawm lub raum poob qis hauv cov pab pawg kho nrog pentoxifylline thaum piv nrog pawg tswj hwm, nrog qhov sib txawv nruab nrab ntawm cov pab pawg ntawm 6.0 mL / min / 1.73 m2, thiab tau sib cav tias cov proteinuria yuav tsis yog ib qho txiaj ntsig zoo tshaj plaws. parameter nyob rau hauv cov kev tshawb fawb no.

Txog niaj hnub no, RCT tseem ceeb tshaj plaws uas ntsuas lub raum tiv thaiv cov teebmeem ntawm pentoxifylline hauv DKD yog Pentoxifylline rau Renoprotection hauv Diabetic Nephropathy (PREDIAN) txoj kev tshawb fawb, luam tawm xyoo 2015 los ntawm Navarro Gonzalez li al. [84]. Txoj kev tshawb no suav nrog 169 hom 2 DM cov neeg mob nrog CKD theem 3 thiab 4 thiab seem albuminuria txawm tias RAS thaiv. Tom qab 2 xyoos ntawm kev soj ntsuam, cov neeg mob randomized rau cov pab pawg neeg nquag (1200 mg / hnub ntawm pentoxifylline nyob rau sab saum toj ntawm RAS blockade) tau nthuav tawm qhov txo qis ntawm kev mob raum, nrog rau eGFR qhov txawv nruab nrab ntawm pawg ntawm 4.3 mL / min / 1.73 m2, nrog rau 14.9 feem pua ​​​​txo qis hauv proteinuria (nce 5.7 feem pua ​​​​hauv pawg tswj). Lub deceleration ntawm qhov poob ntawm GFR nyob rau hauv pentoxifylline caj npab pib thaum lub hli 6 thiab mus txog qhov tseem ceeb ntawm cov ntaub ntawv tom qab 1 xyoo, qhia tias cov txiaj ntsig kho tau tsuas yog pom nyob rau lub sijhawm ntev. Ntxiv mus, cov zis TNF nthuav tawm 10.6 feem pua ​​​​txo qis hauv pawg pentoxifylline, tsis muaj kev hloov pauv hauv pawg tswj hwm.

Cistanche ntxiv

Tam sim no, kev txheeb xyuas lub luag haujlwm tseem ceeb ntawm kev mob o hauv kev txhim kho thiab kev loj hlob ntawm CKD thiab nws cov hom phiaj kho mob ua tau yog qhov tseem ceeb ntawm kev tshawb fawb rau nephrologists. Cov tshuaj tiv thaiv kab mob elicited los ntawm pentoxifylline tau muaj feem xyuam rau cov nyhuv antialbuminuric [93, 113–118]. Hauv qhov no, ib qho tshuaj tiv thaiv kab mob los yog lub raum ua haujlwm khaws cia ntawm pentoxifylline kuj tau pom nyob rau hauv cov neeg mob uas tsis yog ntshav qab zib. Goicoechea et al. [103] qhia txog kev ruaj khov ntawm lub raum ua haujlwm thiab qhov txo qis hauv cov cim ntawm qhov mob, xws li TNF, fibrinogen, thiab siab C-reactive protein (CRP; 45.5, 11.1, thiab 57.4 feem pua ​​​​txo, feem) hauv cov neeg mob theem 3 CKD lossis siab dua uas tau txais kev kho pentoxifylline thaum piv nrog cov tshwj xeeb ntawm RAS thaiv. Proteinuria tsis txo qis hauv cov pab pawg pentoxifylline, txawm hais tias muaj kev tso tawm thiab ua tsis tiav qhov kev soj ntsuam. Lin et al. [104] pom tias pentoxifylline nyob rau sab saum toj ntawm ARB keeb kwm kho mob stabilized GFR thiab txo cov proteinuria (−23.9 feem pua) hauv macroalbuminuric CKD theem 3 cov neeg mob tom qab 1 xyoos ntawm kev soj ntsuam raws li piv nrog ARB monotherapy, rau cov proteinuria nce 13.8 feem pua. Ntxiv mus, pentoxifylline txo cov zis ntawm TNF thiab monocyte chemoattractant protein 1 (MCP-1) (TNF : 42.8 feem pua ​​​​vim 18.8 feem pua ​​​​thiab MCP-1: -28.9 feem pua ​​​​vim 6.2 feem pua, rau pentoxifylline thiab tswj pawg. raws). Ib qho kev txo qis hauv ob qho tib si yog cuam tshuam ncaj qha rau kev hloov pauv hauv proteinuria hauv pawg pentoxifylline. Chen et al. [105] tau tshaj tawm tias 800 mg / hnub pentoxifylline rau 6 lub hlis txo qis proteinuria hauv 17 cov neeg mob uas muaj cov kab mob glomerular thawj [36.5 feem pua ​​​​thiab 33.9 feem pua ​​​​ntawm qhov chaw thiab 24 h proteinuria (g / g Cr)]. Qhov kev txo qis no tau cuam tshuam nrog kev txo qis hauv zis txhais tau tias txo qis ntawm 46 feem pua ​​hauv MCP-1 urinary excretion theem. Hauv kev kawm loj, Chen et al. luam tawm ib qho kev soj ntsuam rov qab ntawm txoj kev tshawb fawb suav nrog 661 cov neeg mob nrog CKD theem 3-5 kho nrog pentoxifylline [106]. Ib zaug ntxiv, pentoxifylline nyob rau sab saum toj ntawm RAS blockade tau muaj kev tiv thaiv lub raum hauv cov neeg mob uas muaj proteinuria ntau dua. Kev sim ua los ntawm Shu et al. [107] tau tshaj tawm txog 19.6 feem pua ​​​​txo qis hauv cov proteinuria hauv lub hlis thib peb thiab txhim kho graft survival los ntawm qhov kawg ntawm txoj kev tshawb no hauv cov neeg tsis muaj ntshav qab zib hloov cov neeg tau txais kev kho mob nrog rau mob allograft nephropathy thiab microalbuminuria kho nrog pentoxifylline tsawg kawg 6 lub hlis.

Ob qhov kev tshuaj ntsuam meta tsis ntev los no tau tshaj tawm cov teebmeem ntawm pentoxifylline ib leeg lossis ua ke nrog lwm cov kev kho mob hauv kev txo qis hauv proteinuria thiab kev khaws cia ntawm lub raum ua haujlwm hauv cov neeg mob ntshav qab zib lossis tsis yog ntshav qab zib CKD. Hauv thawj qhov kev tshuaj ntsuam meta, Leporine li al. [119] xaus lus tias pentoxifylline ua tau zoo hauv kev txo qis proteinuria piv nrog kev tswj hwm, ib qho txiaj ntsig uas pom tseeb dua hauv cov neeg mob hom 1 DM, proteinuria ntau dua ntawm lub hauv paus, thiab lub raum tsis zoo thaum ntxov. Lawv kuj pom muaj kev txhim kho hauv lub raum ua haujlwm (eGFR / creatinine tshem tawm) nyob rau lub sijhawm ntev thiab hauv cov neeg mob uas muaj CKD ntau dua. Nyob rau hauv qhov thib ob meta-analysis, Liu et al. [120] xaus lus tias pentoxifylline ua ke nrog RAS blockade txo cov proteinuria thiab ua rau lub raum tsis ua haujlwm hauv cov neeg mob CKD theem 3-5.

Thaum kawg, kev tshuaj xyuas ntawm cov ntaub ntawv tswj hwm thoob tebchaws ntawm cov neeg mob CKD siab heev txheeb xyuas ob qhov txiaj ntsig zoo sib xws (pentoxifylline cov neeg siv thiab cov neeg tsis siv) tau tshaj tawm tias pawg pentoxifylline tau tiv thaiv los ntawm ESKD [121] Qhov no yog thawj qhov pov thawj ntawm lub peev xwm ntawm pentoxifylline hauv kev txo qis. Kev pheej hmoo ntawm ESKD txawm nyob rau hauv cov neeg mob uas muaj CKD siab heev.

Cistanche tubulosa

Mechanisms ntawm lub raum tiv thaiv los ntawm pentoxifylline

Pentoxifylline yog ib qho methyl-xanthine derivative nrog ntau yam cuam tshuam nrog rau qhov tsis xaiv inhibition ntawm phosphodiesterases (PDEs). Qhov sib npaug ntawm intracellular cyclic adenosine- 3, 5-monophosphate (cAMP), ib qho tseem ceeb hauv lub cellular thib ob signaling messenger, feem ntau yog nyob ntawm kev ua ntawm ob lub enzymes: adenylyl cyclase, uas ua lub luag haujlwm tseem ceeb hauv cAMP synthesis thiab PDEs, uas hydrolyze cAMP [122, 123]. Yog li, qhov inhibition ntawm PDEs los ntawm pentoxifylline tiv thaiv kev degradation ntawm cAMP (Fig. 1). Cov qib cAMP siab, nyob rau hauv lem, txhawb nqa protein kinase A (PKA) ua kom ua rau cov phosphorylation ntawm ntau haiv neeg effectors ua raws li inhibition ntawm kev taw qhia txoj kev koom tes hauv proteinuria thiab lub raum fibrosis [124–126].

PDEs tau tshwm sim los ua lub hom phiaj tseem ceeb rau kev cuam tshuam tshuaj kho mob tiv thaiv CKD kev nce qib [127–129]. Mammalian hlwb muaj 11 tsev neeg cov noob (PDE1–PDE11) thiab txhua tsev neeg suav nrog 1–4 cov noob caj noob ces, muab ˃20 genes nyob rau hauv cov tsiaj nyeg encoding ˃60 txawv PDE isoforms. Hauv vitro, pentoxifylline inhibits PDE3 thiab / lossis PDE4 isozymes los ntawm PKA-dependent txoj kev [124, 126, 130]. Qhov tseem ceeb, PDE3 thiab PDE4 isozymes feem ntau yog qhia hauv monocytes thiab neutrophils [131–133], uas ua rau lawv kho lub hom phiaj ntawm ntau yam kab mob, xws li mob hawb pob, mob ntsws ntsws, mob plab hnyuv, psoriasis, paj hlwb o, thiab rheumatoid. mob caj dab [133]. Pentoxifylline nthuav tawm cov tshuaj tiv thaiv kab mob sib kho los ntawm inhibition ntawm PDEs uas txhawb nqa nws cov peev txheej hauv kev tiv thaiv lub raum ntawm tus neeg mob nrog DM [113-118]. Hauv kev sim ua qauv, pentoxifylline modulates qhia txoj hauv kev los yog cov khoom siv los ntawm inflammatory cytokines. Hauv vitro, pentoxifylline inhibits endotoxin-induced TNF synthesis hauv RAW 264.7 macrophages [108]. Pentoxifylline kuj inhibited endotoxin-induced TNF ntau lawm ob qho tib si nyob rau hauv cov ntshav ntawm nas thiab nyob rau hauv kab lis kev cai adherent peritoneal exudate hlwb [93]. Nyob rau hauv tus qauv nas ntawm crescentic glomerulonephritis, pentoxifylline exerts antiinflammatory thiab immunomodulatory kev ua los ntawm inhibition ntawm lub raum TNF, ICAM-1, RANTES, MCP-1, thiab OPN, yog li suppressing lub raum raug mob [109]. Ib yam li ntawd, pentoxifylline txo qis lub raum qhia ntawm pro-inflammatory cytokines xws li TNF thiab IL6 hauv streptozotocin- lossis alloxan-induced mob ntshav qab zib nas qauv [110, 111], ameliorating lub raum hypertrophy thiab sodium retention [110]. Cov kev sim tshuaj ntsuam xyuas cov tshuaj tiv thaiv kab mob ntawm cov tshuaj no hauv cov neeg mob uas tsis muaj ntshav qab zib tau tshaj tawm cov txiaj ntsig zoo ntawm kev tsim cov cytokines thiab adhesion molecules hauv cov neeg mob uas muaj kab mob plawv thiab atherosclerosis [134, 135]. Ib yam li ntawd, pentoxifylline txo TNF thiab interferon-gamma Tcell qhia hauv ESKD cov neeg mob [136].

Raws li tau tham saum toj no, feem ntau RCTs ntsuas lub raum cuam tshuam ntawm pentoxifylline hauv cov neeg mob DM tau qhia txog kev tiv thaiv lub raum, ua pov thawj los ntawm kev txo qis hauv proteinuria thiab, qee zaum, kev txhim kho lossis kev khaws cia ntawm GFR (Fig. 2). Qhov tseem ceeb, qee qhov RCTs kuj tau pom qhov txo qis hauv cov kab mob inflammatory. Cov nyhuv antiproteinuric ntawm pentoxifylline tau cuam tshuam nrog kev txo qis hauv TNF qib [95, 99]. Ib yam li ntawd, cov kev sim tshuaj tau ua nyob rau hauv cov neeg mob CKD nrog theem 3 lossis siab dua qhia txog kev ruaj khov ntawm lub raum ua haujlwm thiab txo qis ntawm TNF, fibrinogen, thiab CRP tom qab kev kho mob nrog pentoxifylline [118] thiab txo qis hauv proteinuria thiab urinary theem ntawm TNF thiab MCP1 tom qab 1. xyoo ntawm add-on pentoxifylline rau ARB keeb kwm kho mob [104]. Qhov kev sim PREDIAN [84] tau ntsuas lub raum-tiv thaiv cov teebmeem ntawm pentoxifylline hauv DKD cov neeg mob hauv RAS thaiv. Tom qab 2 xyoos, cov neeg mob ntawm pentoxifylline tau nthuav tawm qhov txo qis ntawm cov kab mob raum uas tshwm sim los ntawm kev txo qis hauv cov proteinuria thiab cov zis ntawm TNF. Ob qhov kev tshuaj ntsuam xyuas meta kuj tau taw qhia txog qhov txo qis ntawm proinflammatory cytokines ntau lawm raws li qhov yuav piav qhia tshaj plaws rau cov nyhuv antiproteinuric hauv DKD cov neeg mob [137] thiab xaus lus tias pentoxifylline txo qis proteinuria thiab TNF hauv cov neeg mob DKD tau txais RAS inhibitors [138].

Qhov txiaj ntsig tsis zoo ntawm pentoxifylline hauv cov neeg mob DKD tuaj yeem yog qhov kev txhawb nqa ntawm cov yam ntxwv uas txhawb nqa lub raum noj qab haus huv [139]. Cov protein Klotho yog ib qho tseem ceeb regulator ntawm mineral metabolism feem ntau hais nyob rau hauv lub raum tubular epithelial hlwb thiab, rau ib tug tsawg npaum li cas, nyob rau hauv parathyroid glands, choroid plexus ntawm lub hlwb, vascular ntaub so ntswg, thiab peripheral cov ntshav [140, 141]. Ob hom Klotho tuaj yeem pom: ib leeg-thooj transmembrane protein thiab ib daim ntawv soluble tsim los ntawm proteolytic cleavage ntawm extracellular domain ntawm daim nyias nyias-bound daim ntawv [142]. Soluble Klotho muaj nyob rau hauv cov kua cerebrospinal, tso zis, thiab ntshav, thiab poob rau hauv cov neeg mob CKD nrog kev loj hlob ntawm tus kab mob. Klotho muaj kev tiv thaiv kev laus thiab lub raum tiv thaiv. Kev tiv thaiv kab mob tshwj xeeb ntawm Klotho downregulation tiv thaiv mob raum raug mob hauv nas [143]. Qhov zoo siab, cov neeg mob uas muaj hom 2 DM kuj tseem muaj cov qib Klotho qis dua [144, 145] thiab lub raum Klotho txo ​​qis hauv kev kuaj ntshav los ntawm cov neeg mob uas muaj theem pib ntawm DKD [146]. Muab ua ke, cov ntaub ntawv no taw qhia txog qhov muaj peev xwm siv tau ntawm Klotho ua ib qho biomarker thaum ntxov ntawm lub raum tsis zoo hauv hom 2 DM cov neeg mob thiab rau Klotho downregulation ua tus tsav tsheb ntawm DKD kev loj hlob [147]. Ntxiv mus, Klotho tau inversely cuam tshuam nrog o. Pro-inflammatory cytokines zoo li TNF thiab TWEAK (mob necrosis yam zoo li qaug zog inducer ntawm apoptosis) inhibit lub raum Klotho qhia nyob rau hauv ib qho NF-κB-mediated yam hauv vivo thiab hauv vitro [148–151]. Kev txhais lus kho mob ntawm qhov kev soj ntsuam no tau txais kev txhawb nqa los ntawm kev soj ntsuam tom qab ntawm PREDIAN mus sib hais [84]. Kev tswj hwm ntawm pentoxifylline rau hom 2 DM cov neeg mob nrog CKD theem 3 thiab 4 txo cov ntshav qab zib thiab tso zis TNF thiab nce qib ntshav thiab zis Klotho [85]. Txawm hais tias cov txheej txheem meej tsis paub meej, qhov kev xav ua tau yog tias qhov kev txhawb nqa ntawm Klotho ntau lawm los ntawm pentoxifylline tuaj yeem ua los ntawm nws cov khoom tiv thaiv kab mob, txawm hais tias nyob rau hauv cov kab mob hauv cov kab mob, pentoxifylline ncaj qha tiv thaiv albuminuria-induced downregulation ntawm Klotho qhia [85, 152. ]. Ntxiv mus, pentoxifylline nce tubular cell Klotho saum toj no theem pib, qhia tias kev txhawb nqa lub raum qhia tau yog ib qho ntawm cov txheej txheem ntawm kev tiv thaiv raum los ntawm pentoxifylline. Ntxiv mus, ib qho kev tshawb fawb tau luam tawm tsis ntev los no, tau lees paub qhov txiaj ntsig zoo ntawm kev kho tshuaj ntawm pentoxifylline (10 ug / mL) ntawm Klotho qhia hauv RAW 264.7 hlwb, qhia tias qhov kev tswj hwm no tsis txwv rau lub raum hlwb [153].

Herba Cistanche

Cov lus xaus thiab cov kev xav yav tom ntej

Lub nra hnyav thoob ntiaj teb ntawm ntshav qab zib tau kwv yees tias yuav nce ntxiv nyob rau ntau xyoo tom ntej nyob rau hauv tib lub sijhawm nrog kev rog rog. Ib qho teeb meem tseem ceeb tshaj plaws ntawm ntshav qab zib yog DKD, uas ua rau muaj kev mob plawv thiab kev tuag ntau, txiav txim siab txog kev puas tsuaj loj hauv lub neej zoo. Tseeb tiag, CKD tau teeb tsa los ua qhov thib tsib lub ntiaj teb ua rau tuag los ntawm 2040 [154]. Hauv kev tshawb fawb loj tsis ntev los no, rov qab los ntawm kev tshawb fawb suav nrog 65 000 cov neeg laus nrog hom 2 DM thiab CKD, feem ntau (10 feem pua ​​-17 feem pua) ntawm cov neeg mob tau nthuav tawm cov kab mob tshwm sim dhau qhov kev soj ntsuam nruab nrab ntawm tsuas yog 2 xyoos [153] . Cov kev tshawb fawb yav dhau los kuj tau qhia tias DM yog qhov ua rau muaj kev nce ntxiv ntawm CKD mus rau ESKD piv nrog rau lwm cov kev kwv yees suav nrog cov proteinuria, plawv tsis ua hauj lwm, anemia, thiab siab systolic ntshav siab [155].

Txawm hais tias nrog kev siv dav dav ntawm SGLT2i thiab GLP-1 receptor agonists, qhov kev pheej hmoo tseem ceeb ntawm DKD kev loj hlob tseem nyob. Yog li ntawd, yuav tsum tau nrhiav cov hom phiaj kho mob tshiab thiab cov tswv yim. Pentoxifylline yog ib qho tshuaj uas muaj peev xwm rov ua dua rau kev kho DKD. Txawm hais tias qhov kev rov ua dua ntawm pentoxifylline yog ib lub sijhawm zoo hauv kev muab tus nqi qis rau kev kho tau hauv DKD, ntau yam kev nyuaj tseem nyob. Ib txoj kev tshawb fawb tsis ntev los no tau tshaj tawm tias muaj kev pheej hmoo los ntshav loj hauv cov neeg mob CKD ntawm kev kho pentoxifylline [156]. Cov pejxeem no muaj kev pheej hmoo los ntshav ntau dua vim muaj cov platelet tsis ua haujlwm thiab ntshav ntshav, tshwj xeeb tshaj yog cov neeg mob albuminuria [157, 158].

Raws li tau hais los ntawm Leporini li al. [119] nyob rau hauv kev tshuaj xyuas thiab kev tshuaj ntsuam xyuas meta-txheej txheem tsom rau kev soj ntsuam cov txiaj ntsig ntawm pentoxifylline ntawm cov txiaj ntsig ntawm lub raum hauv cov neeg mob CKD, seb cov tshuaj no puas yuav pab tau rau cov kab mob retarding tseem tsis tau teb rau cov laj thawj tseeb. Ib tug ntawm lawv yog cov heterogeneity ntawm cov kev tshawb fawb txog cov qauv loj, koob tshuaj pentoxifylline, cov pejxeem nyob rau hauv txoj kev tshawb no (CKD theem thiab etiology, proteinuria qib), tswj pawg, thiab concomitant RAS-blocking kev kho mob. RCTs feem ntau yog cov txheej txheem tsis zoo thiab ua tiav nrog cov qauv me me thiab tsuas yog muab cov ntaub ntawv luv luv rau lub raum ua haujlwm ntawm cov ntsiab lus kawg xws li eGFR lossis ntshav creatinine, proteinuria, thiab albuminuria.

Cov kev tshawb fawb yav tom ntej nrog kev soj ntsuam ntev dua, cov qauv loj dua, thiab cov txiaj ntsig nyuaj yuav xav tau. Rau peb txoj kev paub, tam sim no, ob-theem IV kev sim tshuaj ntsuam xyuas tau soj ntsuam cov teebmeem ntawm pentoxifylline hauv kev loj hlob ntawm cov neeg mob DKD. Cov Veterans Affairs (VA) PTXRx (NCT03625648) yog ob qhov muag tsis pom kev, cov tshuaj placebo-tswj, multicentre RCT tsim los soj ntsuam cov nqi hluav taws xob ntawm pentoxifylline, thaum ntxiv rau kev saib xyuas ib txwm, hauv kev txo qis hauv qhov tshwm sim ntawm ESRD lossis kev tuag ntawm cov neeg mob uas muaj hom. 2 mob ntshav qab zib mellitus nrog DKD [159]. Kev tso npe ntawm cov neeg mob rau txoj kev tshawb no (uas kwv yees li ntawm 2510 tus neeg koom) tau pib xyoo 2019 thiab thawj hnub ua tiav yuav yog thaum pib ntawm 2028. Qhov kev sim thib ob hauv chav kawm, PENFOSIDINE (Pentoxifylline Effect in Patients With Diabetic Nephropathy, NCT03664414 ), pib xyoo 2018. PENFOSIDINE suav nrog 196 tus neeg mob nrog DKD thiab cov hom phiaj suav nrog kev ntsuas cov tshuaj tiv thaiv kab mob antioxidant, tiv thaiv kab mob, thiab tshuaj tiv thaiv kab mob uas tau txais pentoxifylline (400 mg / peb zaug ib hnub) rau 2 xyoos. Cov txiaj ntsig ntawm cov kev sim no yuav ua rau pom qhov cuam tshuam ntev ntawm pentoxifylline ntawm ntau yam cim ntawm o, oxidative kev nyuaj siab, thiab fibrosis, ntawm surrogate cov cim ntawm lub raum ua haujlwm xws li txo qis hauv proteinuria thiab kev hloov hauv eGFR, thiab ntawm cov ntsiab lus nyuaj xws li. raws li ESRD thiab tuag.

Cistanche extract

Txawm li cas los xij, ib qho teeb meem tseem ceeb uas ntsib kev rov ua dua ntawm ntau cov tshuaj, suav nrog pentoxifylline, yog qhov tsis muaj kev cuam tshuam rau kev lag luam. Txij li thaum pentoxifylline tau pom zoo rau kev sib cuam tshuam claudication, tsis muaj kev tshawb fawb txog nws cov khoom siv rau lwm yam kab mob ua ntej kev pom zoo lossis ua ntej tas sij hawm ntawm patent. Qhov no txhais tau hais tias cov nyiaj pab rau kev tshawb fawb yav tom ntej yog kev cuam tshuam loj heev txawm tias kev tshawb fawb tam sim no tuaj yeem ua rau pom qhov ua tau zoo ntawm pentoxifylline hauv lwm yam kab mob. Cov tuam txhab lag luam pom tias nws tsis tshua muaj txiaj ntsig rau kev xa rov qab cov peev txheej mus rau cov kev pab cuam rov qab tau muab qhov tsis muaj cov txheej txheem tswj xyuas kom muaj kev tiv thaiv kev lag luam. Tsis tas li ntawd, txawm tias tom qab kev pom zoo ua lag luam, cov ntawv sau tawm thiab tsis muaj ntawv tso cai ntawm cov tshuaj qub qub no tawm me ntsis lossis tsis muaj chaw rau cov txiaj ntsig rau kev lag luam. Yog li ntawd, qhov tseem ceeb ntawm RCTs hauv kev tshawb nrhiav DKD qhia rau pentoxifylline yuav tsum tau txais nyiaj los ntawm tsoomfwv cov kev pabcuam kev sim.

Tsis tas li ntawd, ib qho kev ua tiav tshiab ntawm cov tshuaj repurposed yuav tsum muaj kev paub dav dav ntawm pathogenesis ntawm lub hom phiaj kab mob, nrog rau cov txheej txheem postulated ntawm kev ua ntawm cov tshuaj. Cov ntaub ntawv tam sim no taw qhia rau lub peev xwm ntawm pentoxifylline kom qeeb CKD kev nce qib thaum macroalbuminuria tam sim no, txawm tias nyob rau theem siab ntawm DKD nrog kev kho RAS ntau tshaj plaws. Txawm li cas los xij, txawm hais tias muaj pov thawj rau cov tshuaj tiv thaiv kab mob, cov txheej txheem meej rau cov txiaj ntsig zoo tsis paub thiab tseem tuaj yeem koom nrog kev tsim Klotho. Cov kab mob pathogenic rau DKD tsis to taub, raws li kev piv txwv los ntawm cov khoom siv kho mob tsis zoo thiab qib qis qis tsuas yog ib qho ntawm cov kev cuam tshuam cuam tshuam nrog rau hyperglycemia, hloov pauv lipid metabolism, RAS hyperactivation, thiab kev ua siab ntev. Txawm li cas los xij, qhov kev tshawb fawb tob tob txog qhov kev kho mob zais cia ntawm pentoxifylline thiab nws qhov kev rov ua dua rau DKD cov lus qhia tshiab muaj kev cia siab loj heev los txo qis kev pheej hmoo ntawm lub raum thiab tiv thaiv kev loj hlob ntawm DKD kev sib kis.

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Javier Donate-Correa1,2,3, María Dolores Sanchez-Niño4, Ainhoa ​​González-Luis1,5, Carla Ferri1,5, Alberto Martín-Olivera1,5, Ernesto Martín-Núñez1,3, Beatriz Fernez4c Vernandez-Fern . Tagua1, Carmen Mora-Fernández1,2,3, Alberto Ortiz 4,6, and Juan F. Navarro-González 1,2,3,7,8

1 Unidad de Investigación, Tsev Kho Mob Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain,

2 GEENDIAB (Grupo Español para el estudio de la Nefropatía Diabética), Sociedad Española de Nefrología, Santander, Spain,

3 RICORS2040 (RD21/0005/0013), Instituto de Salud Carlos III, Madrid, Spain,

4 Departamento de Nefrología e Hipertensión, IIS-Fundación Jiménez Díaz thiab Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain,

5 Escuela tsib Doctorado, Universidad de La Laguna, La Laguna, Spain,

6 RICORS2040 (RD21/0005/0001), Instituto de Salud Carlos III, Madrid, Spain,

7 Servicio de Nefrología, Tsev Kho Mob Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain

8 Instituto de Tecnologías Biomédicas, Universidad de La Laguna, Santa Cruz de Tenerife, Spain