Los ntawm Cocer Peptides 
1 month ago
Tag nrho cov kab lus thiab cov ntaub ntawv ntawm cov khoom lag luam muab rau ntawm lub vev xaib no tsuas yog rau cov ntaub ntawv tshaj tawm kev tshaj tawm thiab cov hom phiaj kev kawm.
Cov khoom muab rau hauv lub vev xaib no yog npaj tshwj xeeb rau kev tshawb fawb hauv vitro. Kev tshawb fawb hauv vitro (Latin: * hauv iav *, lub ntsiab lus hauv iav) yog ua los ntawm tib neeg lub cev. Cov khoom no tsis yog tshuaj, tsis tau txais kev pom zoo los ntawm US Food and Drug Administration (FDA), thiab yuav tsum tsis txhob siv los tiv thaiv, kho, lossis kho txhua yam mob, kab mob, lossis mob. Nws raug txwv nruj raws li txoj cai los qhia cov khoom no rau hauv tib neeg lossis tsiaj lub cev hauv txhua daim ntawv.
Txheej txheem cej luam
(1) Cov xwm txheej tam sim no thiab kev pheej hmoo ntawm mob hawb pob thiab mob ntsws ntev
Mob hawb pob yog ib hom kab mob inflammatory kab mob uas muaj ntau thoob ntiaj teb. Nws cov yam ntxwv tseem ceeb suav nrog kev mob ntsws ntev ntev, kev ua pa ntawm lub ntsws hyperresponsiveness, thiab thim rov qab airflow txwv. Cov neeg mob feem ntau muaj cov tsos mob xws li hawb pob, ua tsis taus pa luv, hauv siab nruj, thiab hnoos, uas ua rau lub neej tsis zoo thiab tej zaum yuav ua rau muaj kev hem thawj rau lub neej. Cov kab mob bronchitis feem ntau tshwm sim los ntawm kev mob ntev ntawm lub bronchi, nrog hnoos thiab hnoos qeev ua cov tsos mob tseem ceeb. Qhov xwm txheej tseem nyob tsawg kawg peb lub hlis ib xyoos ib zaug rau ob xyoos sib law liag lossis ntau dua.
(2) Lub luag hauj lwm hauv nruab nrab ntawm kev mob ntsws ntsws hauv mob hawb pob thiab mob ntsws ntev
Kev mob ntsws ntsws asthma
Thaum lub sij hawm txoj kev loj hlob ntawm mob hawb pob, ntau yam inflammatory hlwb xws li eosinophils, mast hlwb, thiab T lymphocytes raug recruited rau hauv cov hlab cua, tso ib tug series ntawm inflammatory mediators thiab cytokines, xws li interleukin-4 (IL-4), interleukin-5 (IL-5), thiab interleukin-13 (IL-13), uas ua rau mob. Cov lus teb inflammatory no ua rau muaj kev puas tsuaj rau cov hlab ntsws epithelium, ua kom cov hnoos qeev tso tawm, ua pa ntawm cov leeg nqaij thiab kho dua tshiab, ua rau cov hlab ntsws hyperresponsiveness thiab airflow txwv.
Daim duab 1 Lub tshuab pa epithelium ua haujlwm tseem ceeb ntawm ib puag ncig thiab lub ntsws.
Mob ntsws ntsws nyob rau hauv Chronic Bronchitis
Cov kab mob hauv cov hlab ntsws hauv cov hlab ntsws ntev yog feem ntau kho los ntawm neutrophils, macrophages, thiab lwm cov hlwb. Cov proteases, reactive oxygen hom, thiab lwm yam khoom tso tawm thaum lub sij hawm inflammatory txheej txheem ua rau cov hlab ntsha thiab ua hauj lwm, ua rau thickening ntawm cov hlab cua phab ntsa thiab nqaim ntawm lub lumen, yog li impairing roj pauv. Lub sijhawm ntev inflammatory stimulation tuaj yeem txhawb txoj kev loj hlob ntawm cov kab mob thiab ua rau muaj kev pheej hmoo ntawm cov teeb meem xws li lub ntsws ua haujlwm tsis zoo thiab kab mob plawv.
(4) Kev tshawb fawb keeb kwm ntawm Bronchogen ua ib tus neeg muaj peev xwm kho tau
Muab rau lub xeev tam sim no ntawm kev kho mob rau cov hlab ntsws o nyob rau hauv mob hawb pob thiab mob bronchitis, txheeb xyuas cov tshiab, muaj kev nyab xeeb, thiab cov neeg ua haujlwm kho mob tau txais txiaj ntsig tseem ceeb hauv kev kho mob. Bronchogen tuaj yeem hloov kho cov lus teb inflammatory los ntawm ntau txoj hauv kev, muaj peev xwm tiv thaiv txoj hlab ntsws o hauv cov neeg mob hawb pob thiab mob ntsws ntev, yog li pab kho cov mob no.
Inhibitory nyhuv ntawm bronchogen rau kev ua pa ntawm txoj hlab ntsws hauv cov neeg mob hawb pob
(1) Kev tswj cov teebmeem ntawm cov kab mob o
Eosinophils
Eosinophils ua lub luag haujlwm tseem ceeb hauv kev ua pa ntawm txoj hlab ntsws hauv hawb pob. Cov tshuaj lom uas lawv tso tawm, xws li eosinophil cationic protein, tuaj yeem ua rau cov hlab ntsha hauv cov hlab ntsha thiab ua rau cov kab mob ua rau mob hnyav. Bronchogen tuaj yeem cuam tshuam cov chemotaxis thiab ua kom cov eosinophils, txo lawv cov infiltration rau hauv cov hlab ntsha. Los ntawm kev tswj cov kev qhia ntawm chemokine receptors, tshwj xeeb tshaj yog CC chemokine receptor 3 (CCR3), nws thaiv cov adhesion ntawm eosinophils thiab cov hlab ntsws epithelial hlwb nrog rau cov hlwb endothelial, yog li txo lawv cov aggregation hauv cov ntaub so ntswg.
T lymphocytes
Th2 hlwb yog cov tshuaj tiv thaiv kab mob tseem ceeb hauv kev mob ntsws asthma, zais cov cytokines xws li IL-4, IL-5, thiab IL-13, txhawb nqa eosinophil ua kom muaj zog thiab ua pa hauv pa. Bronchogen inhibits Th2 cell sib txawv thiab muaj nuj nqi, txo cov zus tau tej cov cytokines. Bronchogen tseem tswj cov naj npawb thiab kev ua haujlwm ntawm kev tswj hwm T hlwb (Tregs), txhim kho Tregs ' inhibitory nyhuv ntawm Th2 hlwb, tswj kev tiv thaiv kab mob, thiab txo cov hlab ntsws o.
Mast cells
Mast hlwb sai tso cov inflammatory mediators xws li histamine thiab leukotrienes thaum lub sij hawm mob hawb pob, ua rau cov hlab ntsha du nqaij contraction thiab nce vascular permeability. Bronchogen stabilizes mast cell membranes, inhibits degranulation, thiab txo cov kev tso tawm ntawm inflammatory mediators, li no alleviating mob ntsws o.
(2) Kev cuam tshuam rau inflammatory mediators thiab cytokines
Txo qhov tso tawm ntawm inflammatory mediators
Ntxiv nrog rau inhibiting kev tso tawm ntawm histamine thiab leukotrienes los ntawm mast hlwb, Bronchogen kuj txo cov theem ntawm lwm yam inflammatory mediators, xws li prostaglandin D₂ (PGD₂) thiab thromboxane A₂ (TXA₂). Cov inflammatory mediators yuav ua rau bronchial du nqaij contraction, nce mucus secretion, thiab vasodilation, exacerbating bronchial o. Los ntawm inhibiting cov kev ua ntawm enzymes xws li cyclooxygenase (COX), Bronchogen txo cov synthesis ntawm PGD₂ thiab TXA₂, yog li alleviating bronchial inflammatory teb.
Kev cai ntawm Cytokine Network
Raws li tau hais ua ntej, cov neeg mob hawb pob pom qhov tsis sib xws ntawm ntau yam cytokines hauv cov hlab ntsws, nrog rau theem siab ntawm Th2-type cytokines xws li IL-4, IL-5, thiab IL-13, thaum cov tshuaj tiv thaiv cytokines zoo li IL-10 raug txo. Bronchogen tuaj yeem txhim kho qhov kev qhia ntawm cov tshuaj tiv thaiv cytokines xws li IL-10, thaum inhibiting zus tau tej cov pro-inflammatory cytokines xws li IL-4, IL-5, thiab IL-13, yog li kho cytokine network imbalances thiab txo cov hlab ntsws o. Bronchogen tseem inhibits cov haujlwm ntawm cytokines xws li qog necrosis factor-α (TNF-α) thiab interferon-γ (IFN-γ), uas tseem ua lub luag haujlwm tseem ceeb hauv kev mob ntsws asthma hauv txoj hlab ntsws thiab kho txoj hlab ntsws.
Daim duab 2 Asthma, ib tug mob inflammatory kab mob nyob rau hauv lub ntsws, yog yus muaj los ntawm eosinophilic o, hnoos qeev hypersecretion, goblet cell hyperplasia, pa cua hyper-xws li, thiab ua tsis taus pa.
(3) Kev tiv thaiv kev tiv thaiv ntawm cov hlab ntsws epithelial
Txo cov epithelial cell puas
Kev mob ntsws asthma tuaj yeem ua rau muaj kev puas tsuaj rau cov hlab ntsws epithelial, ua rau cov hlab ntsha tsis muaj zog. Bronchogen txhawb kev kho thiab rov tsim dua tshiab ntawm cov hlab ntsws epithelial, txhim kho lawv cov kev ua haujlwm. Bronchogen upregulates cov kev qhia ntawm nruj hlws ris proteins xws li occludin thiab nruj junction protein-1 (ZO-1), tswj nruj junctions ntawm epithelial hlwb thiab txo cov influx ntawm inflammatory mediators thiab allergens.
Inhibition ntawm ntau heev mucus secretion
Cov hnoos qeev ntau dhau hauv cov hlab ntsws yog ib qho ntawm cov yam ntxwv tseem ceeb ntawm kev mob ntsws asthma. Cov hnoos qeev ntau dhau tuaj yeem cuam tshuam rau txoj hlab cua thiab ua rau muaj kev txwv tsis pub muaj cua. Bronchogen txo cov mucus synthesis thiab secretion los ntawm inhibiting kev qhia ntawm mucin (MUC) noob nyob rau hauv cov hlab ntsws epithelial hlwb. Tsis tas li ntawd, nws tswj cov mucociliary clearance muaj nuj nqi, txhawb kev tshem tawm cov hnoos qeev los ntawm txoj hlab pas thiab tswj txoj hlab pa patency.
(4) Qhov cuam tshuam rau kev hloov kho cua
Inhibiting smooth nqaij cell proliferation thiab migration
Kev hloov pauv ntawm txoj hlab ntsws yog ib qho tseem ceeb ntawm kev hloov pauv hauv kev mob ntsws asthma, suav nrog kev ua kom tawv nqaij ntawm cov hlab ntsws du thiab tso tawm ntawm extracellular matrix. Bronchogen inhibits qhov kev loj hlob thiab kev tsiv teb tsaws ntawm cov hlab ntsws ntawm cov leeg nqaij, txo lawv cov naj npawb thiab ntim. Los ntawm kev tswj cov kev qhia ntawm cov kab mob ntawm cov kab mob ntsig txog cov protein, cyclin-dependent kinases (CDKs), thiab cyclins, Bronchogen ua rau cov leeg nqaij hauv cov hlab ntsws kom ntes tau nyob rau theem tshwj xeeb ntawm lub voj voog ntawm tes, yog li inhibiting lawv proliferation.
Txo cov extracellular matrix deposition
Thaum kho mob ntsws asthma, fibroblasts synthesize thiab secrete ntau dhau ntawm cov khoom siv ntawm cov cellular matrix xws li collagen thiab fibronectin, uas ua rau cov phab ntsa ntawm cov hlab ntsws thickening. Bronchogen tuaj yeem cuam tshuam qhov ua kom thiab kev loj hlob ntawm fibroblasts, txo cov synthesis thiab deposition ntawm extracellular matrix Cheebtsam. Nws tseem tuaj yeem tswj hwm qhov sib npaug ntawm cov matrix metalloproteinases (MMPs) thiab lawv cov ntaub so ntswg inhibitors (TIMPs), txhawb kev degradation ntawm extracellular matrix thiab alleviating qhov kev kho ntawm txoj hlab pa.
Bronchogen's inhibitory nyhuv ntawm cov hlab ntsws o nyob rau hauv cov neeg mob uas mob bronchitis
(1) Kev tswj hwm ntawm inflammatory cell recruitment thiab activation
Neutrophils
Neutrophils tswj cov hlab ntsws o nyob rau hauv cov mob bronchitis, thiab cov proteases uas lawv tso tawm, xws li elastase, tuaj yeem ua rau cov kab mob ua pa. Bronchogen tuaj yeem inhibit neutrophil chemotaxis thiab ua kom, txo lawv cov tsub zuj zuj hauv cov hlab ntsha. Los ntawm inhibiting kev qhia ntawm integrins nyob rau saum npoo ntawm neutrophils, xws li β₂ integrin, nws txo cov adhesion ntawm neutrophils rau endothelial hlwb, yog li txo lawv tsiv teb tsaws mus rau hauv cov ntaub so ntswg.
Macrophages
Macrophages tsis tsuas yog koom nrog cov kab mob tshem tawm thaum lub sij hawm inflammatory txheej txheem ntawm bronchitis, tab sis kuj tso tawm ntau yam inflammatory mediators. Bronchogen tuaj yeem tswj hwm lub xeev polarization ntawm macrophages, txhawb lawv cov kev hloov pauv mus rau hauv cov tshuaj tiv thaiv kab mob (M2-hom) macrophages, yog li txo qis kev tso tawm ntawm cov cytokines pro-inflammatory xws li IL-1β thiab TNF-α thaum nce qhov tso tawm ntawm cov tshuaj tiv thaiv cytokines xws li IL-10, yog li ua rau mob ntsws.
(2) Qhov cuam tshuam rau Inflammatory Mediators thiab Proteases
Txo Cov Kab Mob Kab Mob Nruab Nrab
Hauv cov neeg mob uas muaj kab mob ntsws ntev, ntau yam kab mob sib kis tau nce siab hauv cov hlab ntsws, xws li IL-8 thiab leukotriene B₄ (LTB₄). Cov inflammatory mediators nyiam neutrophils thiab lwm cov hlwb inflammatory, exacerbating inflammatory teb. Bronchogen tuaj yeem cuam tshuam kev tsim khoom thiab tso tawm cov inflammatory mediators los ntawm suppressing lub activation ntawm inflammatory signaling txoj kev xws li nuclear factor-κB (NF-κB), yog li txo cov noob transcription thiab synthesis ntawm inflammatory mediators.
Inhibiting kev ua ntawm protease
Proteases tso tawm los ntawm neutrophils, xws li elastase thiab cathepsin, tuaj yeem degrade elastic fibers thiab collagen nyob rau hauv cov hlab ntsha, ua rau puas tsuaj rau cov phab ntsa hauv pa. Bronchogen muaj protease inhibitory kev ua si, ncaj qha inhibiting kev ua ntawm cov proteases thiab txo kev puas tsuaj rau cov hlab ntsws cov ntaub so ntswg. Nws tseem tuaj yeem tswj hwm qhov sib npaug ntawm cov proteases thiab lawv cov inhibitors, nce qib ntawm protease inhibitors xws li α₁-antitrypsin, ntxiv txo qis protease-vim kev puas tsuaj rau cov hlab ntsha.
(3) Kev txhim kho ntawm txoj hlab pa mucus hypersecretion thiab ciliary muaj nuj nqi
Txo cov mucus secretion
Cov neeg mob uas mob bronchitis feem ntau muaj cov hnoos qeev tso rau hauv cov hlab ntsha, ua rau hnoos thiab hnoos qeev ntau dua. Bronchogen tuaj yeem txo cov mucus synthesis thiab secretion los ntawm inhibiting kev qhia ntawm MUC noob nyob rau hauv cov hlab ntsha epithelial hlwb. Nws tseem tuaj yeem tswj hwm lub cev physicochemical ntawm cov pa hauv pa, txo nws cov viscosity thiab ua kom yooj yim rau kev tshem tawm.
Txhim kho ciliary muaj nuj nqi
Ib txwm ciliary txav nyob rau hauv cov hlab ntsha yog ib qho tseem ceeb mechanism rau tshem tawm cov hlab ntsha secretions. Nyob rau hauv cov neeg mob uas muaj mob bronchitis, impaired ciliary muaj nuj nqi ua rau mucus clearance. Bronchogen txhawb kev kho thiab rov tsim dua tshiab ntawm cov hlab cua ciliated hlwb, txhim kho ciliary ntaus zaus thiab amplitude, yog li txhim kho mucociliary clearance muaj nuj nqi. Qhov no pab nyob rau hauv lub tshem tawm ntawm secretions thiab pathogens los ntawm txoj hlab pas, alleviating pa pa o.
(4) Kev tiv thaiv ntawm txoj hlab cua thiab kev ua haujlwm
Txo cov hlab cua phab ntsa tuab
Mob ntsws o tuaj yeem ua rau cov phab ntsa ntawm cov hlab ntsws ua kom tuab thiab ua rau cov lumen nqaim hauv cov neeg mob uas muaj mob bronchitis. Bronchogen txo qhov loj ntawm cov hlab ntsha phab ntsa tuab los ntawm inhibiting infiltration ntawm cov hlwb inflammatory, txo kev puas tsuaj los ntawm inflammatory mediators thiab proteases, thiab tswj cov metabolism hauv extracellular matrix, yog li tswj cov qauv ib txwm thiab patency ntawm cov hlab ntsha.
Txhim kho lub ntsws ua haujlwm
Los ntawm kev txo cov hlab ntsws o, txo qis hnoos qeev, txhim kho ciliary muaj nuj nqi, thiab tiv thaiv txoj hlab ntsws, Bronchogen pab txhim kho lub ntsws ua haujlwm hauv cov neeg mob bronchitis. Cov kev tshawb fawb tau pom tias tom qab kev kho mob nrog Bronchogen, cov neeg mob lub ntsws ua haujlwm tsis zoo xws li yuam kom lub ntim ntim hauv ib thib ob (FEV₁) thiab yuam kom muaj peev xwm tseem ceeb (FVC) tau ua kom zoo dua qub, thiab cov tsos mob xws li dyspnea tau txo qis.
Xaus
Hauv cov ntsiab lus, Bronchogen, raws li cov tshuaj muaj peev xwm los kho cov hlab ntsws o hauv kev mob ntsws asthma thiab mob ntsws ntev, muaj ntau lub hom phiaj, ntau txoj hauv kev los tiv thaiv kev ua haujlwm. Los ntawm kev tswj cov kab mob inflammatory, inflammatory mediators, cov hlab ntsws epithelial hlwb, thiab kho txoj hlab pa, Bronchogen zoo suppresses cov hlab ntsws o nyob rau hauv cov neeg mob hawb pob thiab mob bronchitis, txhim kho txoj hlab ntsws qauv thiab kev ua haujlwm, thiab txhim kho cov neeg mob lub neej zoo.
Qhov chaw
[1] Leej Tub JW, Lim S. Glucagon-Zoo li Peptide-1 Raws Li Kev Kho Mob: Ib Ntus Tshiab hauv Kev Tswj Kev Noj Qab Haus Huv [J]. Endocrinology thiab Metabolism, 2024,39(2):206-221.DOI:10.3803/EnM.2024.1940.
[2] Hough KP, Curtiss ML, Blain TJ, et al. Airway Remodeling in Asthma[J]. Frontiers in Medicine, 2020, Volume 7.DOI:org/10.3389/fmed.2020.00191.
[3] Athari S. S. Targeting cell signaling in allergic asthma[J]. Kev Hloov Pauv Teeb Meem thiab Lub Hom Phiaj Kho Mob, 2019,4(1): 45.DOI: 10.1038/s41392-019-0079-0.
Cov khoom muaj rau kev tshawb fawb siv nkaus xwb:
