Ntu Ⅰ: Lub Sij Hawm Ntev Dipeptidyl Peptidase 4 Inhibition ua rau mob ntshav siab thiab lub raum thiab mob plawv tsis zoo nyob rau hauv cov rog uas muaj ntshav siab ntshav siab tsis ua haujlwm nas.

Hu rau: Audrey Huaudrey.hu@wecistanche.com

Edwin K.Jackson; Zaichuan Mi; Delbert G. Gillespie; Dongmei Cheng; Stevan P. Tofovic

POB ZEB: The long-term effects of dipeptidyl peptidase 4 (DPP4) inhibitors on blood pressure and cardiovascular and renal health remain controversial, Herein, we investigated the extended (>182 hnub) cuam tshuam ntawm DPP4 inhibition nyob rau hauv tus qauv ntawm spontaneous hypertension, plawv tsis ua hauj lwm, ntshav qab zib mellitus, rog rog thiab hyperlipidemia.

METHODES AND RESULTS:Cov neeg laus rog rog spontaneously hypertensive lub plawv tsis ua hauj lwm nas (SHHF) tau implanted nrog xov tooj cua transmitters rau kev ntsuas ntawm arterial ntshav siab. Ob lub lis piam tom qab, SHHF tau randomized kom tau txais DPP4 inhibitor (sitegliptin, 80 mg / kg ib hnub hauv dej haus) lossis cov placebo. Thaum kawg ntawm kev ntsuas radiotelemetry, lub raum thiab lub plawv ua haujlwm thiab histology, nrog rau lwm yam kev ntsuas biochemical, tau raug soj ntsuam. Thawj 25 hnub, txhais tau tias cov ntshav siab hauv cov hlab ntsha zoo sib xws hauv sitagliptin-kho tiv thaiv SHHF; Tom qab ntawd, txhais tau tias cov ntshav siab nce ntxiv hauv sitagliptin-kho SHHF (P<0.000001). the="" time-averaged="" mean="" arterial="" blood="" pressures="" from="" day="" 26="" through="" 182="" were="" 7.2="" mm="" hg="" higher="" in="" sitagliptin-treated="" shhf.="" similar="" changes="" were="" observed="" for="" systolic="" (8.6="" mm="" hg)="" and="" diastolic="" (6.1="" mm="" hg)="" blood="" pressures,="" and="" sitagliptin="" augmented="" hypertension="" throughout="" the="" light-dark="" cycle.="" long-term="" sitagliptin="" treatment="" also="" increased="" kidney="" weights,="" renal="" vascular="" resistance.="" the="" excretion="" of="" kidney="" injury="" molecule-1="" (indicates="" injury="" to="" proximal="" tubules),="" renal="" interstitial="" fibrosis,="" glomerulosclerosis,="" renal="" vascular="" hypertrophy,="" left="" ventricular="" dysfunction,="" right="" ventricular="" degeneration,="" and="" the="" ratios="" of="" collagen="" iv/collagen="" il="" and="" collagen="" iv/laminin="" in="" the="" right="">

Cov ntsiab lus:Cov kev tshawb pom no qhia tau hais tias, hauv qee qhov keeb kwm ntawm caj ces, kev kho mob ntev DPP4 inhibitor yog teeb meem thiab txheeb xyuas tus qauv tsiaj los kawm txog cov txheej txheem ntawm, thiab sim txoj hauv kev los tiv thaiv, DPP4 inhibitor-induced pathological mob.

Lo lus tseem ceeb:dipeptidyl peptidase 4 inhibitors, lub plawv puas, kub siab, raum puas, spontaneously hypertensive tsis ua hauj lwm nas.

Lub raum tiv thaiv nyhuv ntawm Cistanche

Dipeptidyl peptidase 4 (DPP4) inhibitors (DPP4ls; piv txwv li, sitagliptin, saxagliptin, thiab alogliptin) yog ib hom tshuaj tiv thaiv kab mob ntshav qab zib uas siv ntau ntau hauv incretin los ntawm inhibiting lawv cov metabolism los ntawm DPP4. Vim tias kev ua kom muaj zog ntawm incretin receptors augmenting insulin tso tawm thiab inhibits glucagon secretion, DPP4I kho txhim kho cov piam thaj homeostasis.1.2

Txawm li cas los xij, muaj cov pov thawj tseem ceeb, uas DPP4s tau txais txiaj ntsig zoo tshaj plaws ntawm cov hlab plawv thiab lub raum hauv cov neeg mob uas muaj hom 2 mob ntshav qab zib mellitus. Piv txwv li, SAVOR-TIMI 53 (Saxagliptin Kev Soj Ntsuam ntawm Vascular Cov txiaj ntsig tau sau tseg hauv cov neeg mob ntshav qab zib mellitus [SAVOR]-Thrombolysis hauv Myocardial Infarction [TIM]53) kev sim qhia tias saxagliptin nce mus pw hauv tsev kho mob rau lub plawv tsis ua haujlwm, ua rau lub raum tsis ua haujlwm thiab ua rau tsis zoo. nce tag nrho-ua rau kev tuag. Txawm hais tias kev tshuaj xyuas ntawm EXAMINE (Kev kuaj mob plawv nrog Alogliptin vs Standard of Care in Patients with Type 2 Diabetes Melltus thiab Acute Coronary Syndrome) txoj kev tshawb fawb xaus lus tias alogliptin tsis ua rau tag nrho tsev kho mob rau lub plawv tsis ua hauj lwm, 4 qhov kev soj ntsuam no tau nthuav tawm qhov nce ntxiv. Tus nqi ntawm kev mus pw hauv tsev kho mob rau lub plawv tsis ua hauj lwm nyob rau hauv ib pab pawg neeg ntawm cov neeg mob uas tsis muaj keeb kwm ntawm lub plawv tsis ua hauj lwm uas tau kho nrog alogliptin.4 Tseeb tiag, Pawg Neeg Saib Xyuas Khoom Noj thiab Tshuaj Hauv Tebchaws Meskas tau txiav txim siab tias alogliptin nce mus pw hauv tsev kho mob rau lub plawv tsis ua haujlwm. Raws li qhov kev txiav txim siab no, ntau cov kev tshawb fawb soj ntsuam tau xaus lus tias DPP4Is nce mus pw hauv tsev kho mob rau lub plawv tsis ua hauj lwm.5.6A kev tshuaj ntsuam xyuas meta-tshaj nrog 54 qhov kev sim rau npe 74 737 cov neeg mob tau sau tseg qhov ze-qhov tseem ceeb 10.6 feem pua ​​​​nce kev pheej hmoo ntawm kev mus pw hauv tsev kho mob rau cov neeg mob plawv. noj DPP4ls.7 Ntxiv mus, Chen thiab al xaus lus tias sitagliptin tsis muaj cov txiaj ntsig ntawm cov hlab plawv, tab sis ua rau muaj kev pheej hmoo ntawm myocardial infarction thiab coronary revascularization, thiab PROLOGUE (Txoj Haujlwm Kev Ntsuam Xyuas Vascular hauv qab Glucose Control los ntawm DPP-4 Inhibitor) txoj kev tshawb nrhiav pom tsis muaj pov thawj tias sitagliptin txo qis qhov kev loj hlob ntawm carotid intima-medial thickness.9 Qhov zoo tshaj plaws, cov txiaj ntsig ntawm cov hlab plawv cov txiaj ntsig tau pom tias DPP4ls tsis txhim kho cov hlab plawv tuag, tsis tuag myocardial infarction, lossis mob stroke.2 Qhov no yog qhov tsis sib xws rau glucagon. -zoo li peptide-1 receptor agonists (GLP-1RAs), uas qhia meej txog cov txiaj ntsig ntawm lub plawv thiab lub raum hauv pat Cov neeg uas muaj hom 2 mob ntshav qab zib mellitus los ntawm kev ua haujlwm ncaj qha rau incretin receptors.2

Cistanche acteoside rau lub raum noj qab haus huv

Kev nkag siab zoo dua vim li cas DPP4ls tsis ua haujlwm, txheeb ze rau GLP-1RAs, hais txog kev txhim kho cov hlab plawv thiab lub raum cov txiaj ntsig hauv cov neeg mob uas muaj ntshav qab zib hom 2 tuaj yeem nthuav qhia cov ntsiab lus tseem ceeb ntawm kev ua, thiab kev kho mob rau, kab mob plawv thiab raum. thiab tej zaum yuav qhia txoj hauv kev los txhim kho cov txiaj ntsig nrog kev kho DPP4I. Dab tsi yuav tsum tau ua kom tiav cov hom phiaj no yog tus qauv tsiaj txhim khu kev qha uas DPP4ls txhim kho glycemic tswj tsis tau ua rau lub plawv thiab lub raum tshwm sim. Los ntawm kev siv cov qauv tsiaj zoo li no, nws yuav ua tau kom paub meej txog cov hauv qab no: (1) uas cov tshuab biochemical tau qhib los ntawm DPP4ls neutralize cov txiaj ntsig ntawm cov hlab plawv thiab lub raum ntawm DPP4ls hauv cov neeg mob; (2) uas cov neeg mob yuav tau txais txiaj ntsig zoo tshaj plaws los ntawm kev kho DPP4I; thiab (3) cov kev kho mob dab tsi tuaj yeem ua ke nrog DPP4ls los txhim kho cov txiaj ntsig ntawm tus neeg mob.

Hmoov tsis zoo, qhov tsis sib xws rau cov neeg mob ntshav qab zib mellitus, tsiaj cov qauv ntawm cov ntshav qab zib mellitus yog qhov nyuaj thiab tsis tu ncua qhia cov txiaj ntsig zoo ntawm lub raum thiab cov hlab plawv nrog DPP4I txoj kev kho. sitagliptin ntawm ntshav siab hauv cov qauv tsiaj. Hauv qhov no, peb tau pom tias sitagliptin nce ntshav siab hauv cov nas muaj ntshav siab (SHR), tsis muaj kev cuam tshuam rau cov ntshav siab hauv cov nas tsis muaj zog Wistar-Kyoto (WKY), thiab yog cov tshuaj tiv thaiv kab mob hauv cov nas uas muaj ntau yam uas tau tsav los ntawm cov kab mob metabolic. (Zucker mob ntshav qab zib Sprague-Dawley nas).23 Vim tias cov kev tshawb fawb no siv tib cov tshuaj, tib koob tshuaj, thiab cov qauv kev sim tib yam, tseem ua rau muaj txiaj ntsig zoo sib txawv ntawm cov ntshav siab, peb tau txiav txim siab tias cov teebmeem ntawm DPP4ls yog cov ntsiab lus nyob ntawm.24

Lub raum teebmeem ntawm tshuaj ntsuab cistanche

Qhov tseeb tias sitagliptin ua rau mob ntshav siab hauv SHR, tab sis tsis cuam tshuam rau cov ntshav siab hauv WKY lossis Zucker cov kab mob ntshav qab zib Sprague-Dawley nas, txhawb txoj kev tshawb fawb tam sim no los tshawb xyuas qhov "ntev" cov teebmeem ntev ntawm sitagliptin hauv cov rog rog spontaneously hypertensive cov nas tsuag ( SHHF). Vim tias rog rog SHHF muaj SHR caj ces keeb kwm yav dhau los, lawv yuav tsum nkag siab txog qhov tsis zoo ntawm DPP4ls. Tsis tas li ntawd, vim tias SHHF muaj cov phenotype uas suav nrog cov kab mob metabolic (kev rog, ntshav qab zib mellitus, dyslipidemia, thiab kub siab) thiab mob plawv thiab lub raum pathological nta thiab tsis ua haujlwm, 25 lawv yuav tsum nkag siab ntau dua rau qhov tsis zoo ntawm cov hlab plawv thiab lub raum cuam tshuam ntawm DPP4ls thiab yuav tsum zoo dua. qauv cov pej xeem ntawm cov neeg mob feem ntau sau DPP4ls. Yog li ntawd, peb xav tias tus qauv tsiaj no yuav zoo tagnrho rau kev nthuav tawm qhov tsis zoo ntawm DPP4ls. Txoj kev tshawb fawb tam sim no qhia meej meej tias, nyob rau hauv qhov tsim nyog keeb kwm ntawm caj ces (cov ntsiab lus), kev siv txuas ntxiv ntawm DPP4ls nce ntshav siab thiab ua rau lub plawv thiab lub raum cov qauv thiab kev ua haujlwm. Cov kev tshawb pom no muaj feem cuam tshuam rau kev siv tam sim no ntawm DPP4Is thiab qhia tias rog rog SHHF yuav yog ib qho qauv zoo rau kev ua tiav kev nkag siab zoo ntawm cov tshuaj pharmacological ntawm DPP4ls. Qhov kev nkag siab zoo dua no tuaj yeem txhim kho txoj kev kho mob nrog DPP4ls thiab txheeb xyuas cov hom phiaj tshiab rau cov tshuaj tiv thaiv thiab kho cov kab mob plawv thiab lub raum.

Cistanche ntxivrau lub raum noj qab haus huv

Lus Cim: Cov tshuaj suav tshuaj suav tshuaj ntsuab cistanche (tseem hu ua "daj tshuaj ntsuab" thiab "tso suab puam ginseng"), loj hlob tsuas yog hauv cov suab puam qhuav thiab sov. Raws li ib qho ntawm cuaj cov tshuaj tsis txawj tuag, Cistanche (cistanche tubulosa / cistanche deserticola / desertliving cistanche / cistanche salsa) cov ntsiab lus nrog cov khoom xyaw nplua nuj xws li echinacoside, acteoside, tag nrho phenylethanoid glycosides, flavonoids, polysaccharides, thiab lwm yam. nourishing tshuaj ntsuab thiab khoom noj khoom haus rau tib neeg lub cev tiv thaiv kab mob, cov kab mob hauv nruab nrog cev, thiab hlwb hlwb thiab neurons, thiab lwm yam. Cov kev tshawb fawb tshuaj niaj hnub no tau lees paub cov txiaj ntsig ntawm cistanche (cov txiaj ntsig ntawm cistanche): txhim kho kev tiv thaiv; txhim kho kev ua haujlwm ntawm kev sib deev thiab lub raum ua haujlwm; tiv thaiv qaug zog; anti-aging; txhim kho kev nco; anti-Parkinson tus kab mob; anti-Alzheimer tus kab mob; antioxidation; yooj yim- cem quav; anti-inflammatory; txhawb cov pob txha loj hlob, ua kom tawv nqaij dawb; tiv thaiv daim siab; lwm.