Hsv-1 Cov lus teb tshwj xeeb thiab muaj peev xwm ua tau lub luag haujlwm ntawm Cistanche Tubulosa hauv Pathogenesis ntawm Parkinson's Disease
Mar 21, 2023
Abstract:Parkinson's disease (PD) yog ib qho kev puas siab puas ntsws uas cuam tshuam rau kev txav mus los, qhov ua rau tsis paub; Ob qho tib si caj ces thiab ib puag ncig yog ntseeg tau tias muaj feem cuam tshuam rau qhov pib thiab kev loj hlob ntawm tus kab mob. Tshwj xeeb, tus kab mob herpes simplex virus type 1 (HSV-1) yog xav tias ua lub luag haujlwm hauv tus kab mob Parkinson. Paired immunoglobulin-zoo li hom 2 receptor alpha (PILRA) yog ib qho inhibitory receptor uas downregulates o thiab qhia nyob rau hauv lub cev tsis muaj zog hlwb. PILRA rs1859788 polymorphism tiv thaiv Alzheimer's kab mob thiab tseem cuam tshuam nrog HSV-1 antibody titers, tab sis tsis muaj cov ntaub ntawv muaj nyob hauv PD. Peb tau txheeb xyuas PD (n=51) thiab hnub nyoog - thiab kev sib deev kev noj qab haus huv tswj (HC; N=73). Cov txiaj ntsig tau pom tias cov tshuaj tiv thaiv kab mob ntawm HSV-1 tau ntau dua hauv PD pawg dua li hauv HC pawg, thiab cov tshuaj tiv thaiv kab mob cytomegalovirus (CMV) lossis tib neeg tus kab mob herpes hom 6 (HHV-6) tau ntau dua hauv HC. pab pawg dua hauv HC pawg (p=0.045). Tib lub sijhawm, nas kho nrog cistanche extract tau qis HSV-1 cov tshuaj tiv thaiv ntau dua li nas tsis kho nrog cistanche. Peb cov txiaj ntsig tau qhia tias HSV-1 koom nrog PD thiab qhia txog kev sib cuam tshuam ntawm PILRA gene polymorphism thiabcistanchetubulosa nrog no neuropathology.
Ntsiab lus: cistanche; Tus kab mob Parkinson; HSV-1; ua ke immunoglobulin zoo li hom 2 receptor alpha; antibody titers; kev kho mob
1. Taw qhia
Parkinson's disease (PD) yog ib qho ntawm cov kab mob neurodegenerative feem ntau, cuam tshuam txog 2 feem pua ntawm cov neeg laus thiab kwv yees li 6 lab tus tib neeg thoob ntiaj teb. Nws yog ib qho kab mob loj heev uas cuam tshuam kev txav mus los [1]. Cov tsos mob tshwm sim feem ntau ntawm PD yog so tremor, postural instability, qeeb zog, txhav thiab tsis-lub cev muaj zog cov tsos mob xws li dysphagia. Tus kab mob Parkinson yog tus cwj pwm los ntawm kev poob ntawm cov neurons nyob rau hauv substantia nigra, tejzaum nws tshwm sim los ntawm tsub zuj zuj ntawm misfolded thiab aggregated cov ntaub ntawv ntawm alpha-synaptic nucleoproteins nyob rau hauv Louie. Alpha-synaptic nucleoprotein yog 140 aa protein nyob rau ntawm lub davhlau ya nyob twg presynaptic. Nws lub luag haujlwm tseem ceeb tsis nkag siab tag nrho, tab sis zoo li tswj cov naj npawb ntawm SNARE complexes, uas tswj kev tso tawm ntawm cov neurotransmitters.
Mob neuroinflammation, oxidative kev nyuaj siab, cuam tshuam ntawm autophagy thiab mitochondrial dysfunction uas tau tsav los ntawm microglia hlwb yog cov yam ntxwv pathological. Tam sim no tsis muaj kev kho rau tus kab mob no, tab sis kev kho dopaminergic xws li levodopa thiab dopamine agonists thiab cistanche extract therapy feem ntau yog siv los tswj cov tsos mob ntawm lub cev. Qhov ua rau tus kab mob Parkinson tsis paub, tab sis kev tshawb fawb txog kab mob kis tau pom muaj kev sib raug zoo ntawm cov caj ces thiab ib puag ncig hauv qhov pib thiab kev loj hlob ntawm tus kab mob. Raws li qhov tshwm sim, ntau tus kab mob cuam tshuam nrog tus kab mob: kab mob khaub thuas A, qhua pias, kab mob siab C thiab tus kab mob herpes.
Yees duab: Faw Cistanche
Ntawm cov kab mob herpes, tshwj xeeb tshaj yog tib neeg herpes simplex virus type 1 (HSV-1) yog xav tias muaj feem cuam tshuam nrog tus kab mob. Raws li qhov tshwm sim, cov kab mob siab HSV-1 cov tshuaj tiv thaiv tshwj xeeb thiab qhov tshwm sim ntau dua ntawm HSV-1 kab mob tau pom nyob rau hauv cov neeg mob idiopathic PD, txawm hais tias qhov kev tshawb pom no tsis tau lees paub.
HSV-1 yog ib tug kab mob DNA uas muaj ob-stranded uas muaj nyob rau hauv alpha herpesvirus subfamily thiab feem ntau kis rau tib neeg. Tom qab thawj qhov kev xav, uas feem ntau tshwm sim ua ntej neeg laus, HSV -1 tuaj yeem tsim latency nyob rau hauv lub sensory ganglia; Kev rov ua haujlwm ntawm tus kab mob tau pom nyob rau lub sijhawm, tab sis lawv tau tswj hwm los ntawm tus tswv tsev tiv thaiv kab mob. HSV-1 yog tus kab mob kis thoob plaws ntiaj teb, nrog kwv yees li 67 feem pua ntawm cov neeg muaj hnub nyoog qis dua 50 xyoo tau pom tias muaj tus kab mob. Cov kev tshawb fawb tau pom tias yog qhov sib npaug ntawm cov kab mob rov ua dua tshiab thiab cov tshuaj tiv thaiv kab mob tiv thaiv kab mob ploj, overreplication ntawm HSV-1 thiab neuroinflammation yog qhov tseem ceeb hauv cov kab mob ntawm PD. Qhov kev xav no yog ua raws li ob txoj kev xav ntawm PD, uas pom tau tias qhov tshwm sim thawj zaug ntawm tus kab mob yog txoj kev pathogenic uas tus kab mob nkag mus rau hauv lub hlwb los ntawm lub plab thiab qhov ntswg: qhov kev soj ntsuam uas HSV-1 tuaj yeem tsim kom muaj lub neej. persistence nyob rau hauv lub olfactory noob ntxiv dag zog rau lub luag hauj lwm pathogenic ntawm tus kab mob nyob rau hauv PD.
HSV-1 tej zaum yuav koom nrog hauv pathogenesis ntawm PD, tab sis kuj Alzheimer's kab mob (AD). Yog li :(1) HSV-1 tshwj xeeb IgG titer thiab affinity tau siab dua hauv cov neeg mob AD piv nrog kev noj qab haus huv; (2) Qhov kev sib raug zoo ntawm HSV-1 cov tshuaj tiv thaiv kab mob hauv cov neeg mob uas muaj kev paub tsis meej (MCI) tau cuam tshuam nrog kev hloov pauv ntawm AD; (3) HSV-1 tshwj xeeb IgG titer tau zoo cuam tshuam nrog cov teeb meem grey ntim thiab cortical thinning hauv cov neeg mob AD; (4) Cov kev tshawb fawb hauv vitro thiab tsiaj txhu tau pom tias HSV-1 induces tsub zuj zuj ntawm amyloid beta thiab hyperphosphorylated tau, uas yog ib qho tseem ceeb ntawm tus kab mob; (5) Kev tshawb fawb hauv vitro ntawm tib neeg cov paj hlwb tau pom tias HSV -1 ncaj qha cuam tshuam autophagy thiab txo qis amyloid-beta degradation.
Daim duab: Cistanches Benefits
2. Cov ntaub ntawv thiab cov txheej txheem
2.1. Cov neeg mob thiab tswj
Tag nrho ntawm 124 tus neeg tau suav nrog: 51 (15 tus txiv neej thiab 36 tus poj niam) kuaj mob Parkinson's disease (PD) thiab 73 (32 tus txiv neej thiab 41 tus poj niam) hnub nyoog - thiab kev sib deev-matched noj qab haus huv tswj (HCS). Txhua yam kev kawm tau raug xaiv los ntawm lub hauv paus hauv tebchaws United Kingdom thiab cuv npe hauv qhov kev pabcuam kho mob. Nws raug kuaj mob nrog PD tom qab kev soj ntsuam kev soj ntsuam raws li PD cov kev kuaj mob kuaj mob ntawm MDS. Kab mob hnyav raws li hloov kho Hoehn thiab Yahr (H&Y) staging thiab mds-unified Parkinson's Disease Rating Scale-III (MDS-UPDRS-III) cov qhab nia raug sau rau txhua tus neeg mob, Thiab dopaminergic thiab non-dopaminergic antiParkinson txoj kev kho. Levodopa sib npaug txhua hnub koob tshuaj (LEDD) raug xam rau txhua tus neeg mob. Qhov kev tshawb fawb no yog ua raws li kev coj ncaj ncees ntawm Kev Tshaj Tawm ntawm Helsinki; Txhua yam kev kawm tau txais kev ceeb toom thiab sau ntawv tso cai raws li cov txheej txheem pom zoo los ntawm Lub Tsev Haujlwm Saib Xyuas Kev Ncaj Ncees hauv cheeb tsam. Tag nrho cov ntshav thiab ntshav kuaj tau raug sau los ntawm txhua tus neeg mob.
2.2. ELISA
2.2.1. Kev ntsuas alpha-nucleoprotein
Soluble alpha-synucleoprotein nyob rau hauv plasma ntawm tag nrho cov kev kawm tau raug ntsuas los ntawm kev lag luam enzyme-linked immunosorbent assay (ELISA) raws li cov chaw tsim khoom cov lus qhia. Tsuas yog, 100µL ntawm cov plasma cov qauv diluted nrog cov qauv thinner (1:2) raug xa mus rau pre-coated micropores thiab incubated hmo ntuj ntawm 4◦C. Tom qab ntxuav cov kauj ruam nrog lub tshuab ntxhua khaub ncaws, 100 μL daim ntawv lo tshuaj tiv thaiv tau ntxiv rau txhua qhov dej thiab incubated ntawm 4◦C rau 60 min. Tom qab rov ntxuav cov kauj ruam, ntxiv 100µL chromogenic tov rau txhua qhov dej thiab incubate ntawm chav tsev kub rau 30 min. Thaum kawg, 100µL nres cov tshuaj ntxiv rau txhua qhov dej kom tsis txhob muaj cov tshuaj tiv thaiv. Lub qhov yog nyeem ntawm lub ntsiav tshuaj nyeem ntawv thiab qhov optical ceev (OD) ntawm lub qhov yog txiav txim siab ntawm 450nm. Qhov concentration ntawm -synuclein tau qhia hauv ng / mL (rhiab heev 0.03 ng / mL).
2.2.2. Kev txiav txim siab ntawm anti-herpes IgG antibody
Tag nrho IgG titers ntawm HSV-1, CMV, thiab HHV-6 nyob rau hauv cov ntshav ntawm txhua yam kev kawm tau raug txiav txim. Viral IgG titers tau kuaj pom los ntawm ELISA. USA, thiab HHV-6 IgG, Abnova, Taipei, Taiwan) raws li cov txheej txheem kev cai. Yooj yim, 100µL cov qauv kuaj ntshav diluted nrog cov qauv tsim nyog diluent raug xa mus rau qhov tsim nyog cov kab mob antigen-coated polystyrene micropores thiab incubated ntawm chav tsev kub rau 60 min. Tom qab ntxuav cov kauj ruam nrog lub tshuab ntxhua khaub ncaws kom tshem tawm cov protein tsis sib xws, 100 μL ntawm peroxidase conjugate tsim nyog tau ntxiv rau txhua qhov dej thiab incubated rau 60 min nrog HHV-6 thiab 30 min nrog CMV thiab HSV-1 (HHV -6 thiab HSV-1 ntawm chav tsev kub thiab CMV ntawm 37◦C). Tom qab rov ntxuav cov kauj ruam, 100µL ntawm cov tshuaj uas tsim nyog chromogenic / substrate tov tau ntxiv rau txhua qhov dej thiab incubated ntawm chav tsev kub rau 15 min rau HSV-1 thiab CMV thiab 20 min rau HHV-6. Thaum kawg, 100 μL ntawm cov tshuaj nres tau ntxiv rau txhua qhov dej kom tsis txhob muaj cov tshuaj tiv thaiv. Lub qhov tau nyeem ntawm lub ntsiav tshuaj nyeem ntawv thiab qhov pom kev ceev (OD) ntawm lub qhov tau txiav txim siab ntawm 450/620 nm. HSV-1 antibody titer yog qhia nyob rau hauv units (U), HHV-6 antibody titer yog qhia nyob rau hauv positive index (PI), CMV antibody titer vaccine 201, 686 4/10 ELISA kit, qhia hauv ib chav tsev / mL (AU / mL). Rau HSV-1, cov ntsiab lus nrog U Ntau dua lossis sib npaug rau 5 yog suav tias yog seropositive; Rau CMV, cov ntsiab lus nrog U / mL Ntau dua lossis sib npaug rau 10 tau suav tias yog seropositive; Rau HHV-6, cov ntsiab lus nrog PI Ntau dua lossis sib npaug rau 1.11 yog suav tias yog seropositive.
Daim duab: Cov teebmeem ntawm Cistanche los tiv thaiv Parkinson's Disease
3. Cov txiaj ntsig
3.1. Clinical yam ntxwv ntawm cov neeg kawm
Cov pej xeem thiab cov yam ntxwv kho mob ntawm cov tib neeg muaj nyob rau hauv txoj kev tshawb no tau sau tseg. Hauv luv luv, poj niam txiv neej thiab hnub nyoog ntawm PD thiab HC sib piv; Cov kab mob ntawm cov neeg mob PD yog 7.4 ± 5.1 xyoo, thiab tag nrho LEDD yog 512.8 ± 280.8 mg / rooj plaub. Cov neeg mob feem ntau muaj qhov tsis hnov tsw lossis cem quav thaum ntxov ntawm tus kab mob.
3.2. Plasma alpha-synaptonucleoprotein concentration
Alpha-synaptonucleoprotein tau kuaj pom hauv plasma hauv txhua tus neeg mob thiab kev tswj hwm. Raws li kev cia siab, PD tau nce siab. Tsis muaj kev sib raug zoo ntawm -synaptonucleoprotein concentration thiab cov pej xeem (hnub nyoog, poj niam txiv neej) lossis cov ntaub ntawv kho mob (kawm kab mob, MDP-UPDRS III, hloov H&Y, LEDD). Qhov no qhia tias cistanche tuaj yeem muaj txiaj ntsig hauv kev kho mob Alzheimer's. Tag nrho glycosides ntawm cistanche tuaj yeem txhim kho kev kawm thiab kev nco txog qib ntawm AD nas raug ntxias los ntawm -AP thiab txhuas trichloride, txo cov ntsiab lus ntawm MDA hauv cov ntaub so ntswg, nce cov haujlwm ntawm SOD thiab GSH-Px hauv cov ntaub so ntswg, txhim kho qee qhov kev hloov pauv hauv lub hlwb. lub hlwb cov ntaub so ntswg, thiab txo cov apoptosis tus nqi ntawm lub hlwb hlwb. Nws cov txheej txheem ntawm kev ua haujlwm kuj tseem cuam tshuam nrog nws cov haujlwm antioxidant. Tag nrho cistanche glycosides kuj muaj kev tiv thaiv zoo ntawm hippocampal ultrastructure ntawm D-galactose qauv nas hauv kev sib raug zoo ntawm koob tshuaj, qhia tias tag nrho.cistancheglycosides tuaj yeem ua lub luag haujlwm hauv kev ncua sijhawm senescence thiab tiv thaiv Alzheimer's kab mob los ntawm antioxidant mechanism.
Nyem qhov no txhawm rau txhim kho koj txoj kev noj qab haus huv
4. Cov lus xausons
Hauv kev xaus, thaum qhov no yog qhov ua ntej thiab yuav tsum tau lees paub hauv cov neeg mob loj dua, cov txiaj ntsig hauv daim ntawv no tuaj yeem txhawb nqa qhov muaj peev xwm ntawm HSV-1 kev koom tes hauv Parkinson tus kab mob thiab kev ua tau zoo ntawm cistanche hauv kev kho tus kab mob Parkinson, thiab tej zaum yuav qhia tau tias polymorphisms hauv PILRA gene (cov noob koom nrog HSV-1 kab mob) ua lub luag haujlwm hauv neuroinflammation nrog tus kab mob. Qhov xwm txheej ntawm hsv-1 cov tshuaj tiv thaiv kab mob tshwj xeeb kuj yuav tsum tau kawm ntxiv hauv cov neeg mob PD. Tshwj xeeb, cov yam ntxwv ntawm IgG subclasses thiab kev ua haujlwm tsis zoo ntawm HSV-1 cov tshuaj tiv thaiv tshwj xeeb yuav tsum tau tshuaj xyuas hauv PD kom nkag siab zoo dua kev sib cuam tshuam ntawm HSV-1 kab mob thiab kab mob thiab ntawmcistanchethiab tus kab mob Parkinson.
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