Hauv nruab nrab hnub nyoog, tib neeg ib txwm nthuav qhia qhov mob thiab mob ntawm lub hauv caug thaum lawv nce thiab nqis ntaiv, thiab lub hauv caug thim rov qab thaum lawv khoov lawv cov ceg. Tus kab mob osteoarthritis (OA) no tshwm sim los ntawm nyias thiab mob leeg. Yog li ntawv, tus kabmob sib kis tau tshwm sim los ntawm pob txha mos tsis muaj kev puas tsuaj, kev rhuav tshem thiab pob txha loj hlob tau dhau los ua qhov osteoarthritis tsis tshua muaj neeg nyob hauv Suav teb, uas yog cov kab mob tseem ceeb cuam tshuam rau lub neej zoo tshaj 100 lab tus neeg mob. Txawm li cas los xij, tseem tsis muaj kev kho tau tus kabmob zoo rau lub sijhawm no, thiab nws tseem ceeb rau kev tsim kho cov tshuaj lossis cov tswv yim los kho lossis thim rov qab OA.
Tsis ntev los no, cov kws tshawb fawb los ntawm Pennsylvania State University tau nthuav tawm cov lus hais txog" paradox mediated GRK2 kev kis kab mob yog kev hloov kho kab mob kev kho mob cancer" hauv Kev Tshawb Fawb Kev Tshawb Fawb Kev Tshawb Fawb Kev Tshawb Fawb Kev Tshawb Fawb Raws li kev tshawb fawb ntawm osteoarthritis, paroxetine, uas tau siv yav dhau los, tsis tuaj yeem tsuas yog txo qis pob txha mos tsis zoo thiab ua rau qeeb OA cov txheej txheem, tab sis kuj tseem nrawm pob txha mos matrix tsim dua tshiab thiab txawm rov zoo li qub.
Cov kev tshawb fawb tom ntej tau pom tias OA feem ntau ua rau pob txha mos ua rau los ntawm nyias thiab me me chondrocytes ntawm qhov chaw tseem ceeb. Chondrocytes tau txais kev ua haujlwm los ntawm ntau yam cim ua haujlwm sab hauv coj mus rau transmembrane g-ovalbumin-coupled receptor (GPCR). Qhov nce ntawm g-ovalbumin-coupled receptor kinase 2 (GRK2) qhia hauv cov kab mob hauv lub plawv thiab lub raum yuav ua rau GPCR desensitization, thiab kev loj hlob thiab emaciation ntawm cov kab mob rhiab hlwb, ntawm qhov tsis sib haum, inhibition ntawm GRK2 membrane kev tuaj yeem tuaj yeem rov qab qhov sib npaug ntawm GPCR txias thiab lub teeb liab xa khoom, thiab zam kev loj hlob thiab emaciation ntawm tus kab mob rhiab hlwb. Raws li qhov no, cov kws tshawb nrhiav kwv yees hais tias GRK2 tseem tuaj yeem tiv thaiv kev loj hlob thiab emaciation ntawm chondrocytes.
Txhawm rau tshawb xyuas lub luag haujlwm ntawm GRK2 hauv OA, cov kws tshawb nrhiav ua ntej siv cov tshuaj tiv thaiv kab mob (yog tias) staining txhawm rau txhawm rau txhawm rau paub txog kev qhia ntawm GRK2 nyob rau hauv tib neeg pob txha mos thiab raug mob. Nws tau pom tias piv nrog kev tswj hwm, qhov hais tawm ntawm GRK2 nyob rau hauv pob txha mos ntawm qhov mob (raug mob meniscus) thiab mob OA mob tau nce ntau dua, thiab nws tau ntxiv rau hauv lub sijhawm-sijhawm ua haujlwm CAMP cov ntsiab lus txuas ntxiv. Cov txiaj ntsig no tau qhia tias GRK2 kho kom haum xeeb GPCR desensitization ua lub luag haujlwm tseem ceeb hauv OA kev ncua.
Txhawm rau kom nkag siab ntxiv txog lub luag haujlwm ntawm GRK2 hauv OA ncua thiab nws txoj kev tsis muaj txiaj ntsig raws li lub hom phiaj kho, cov kws tshawb nrhiav tau ua rau chondrocyte tshwj xeeb GRK2 rho tawm qhov induction hauv OA mouse qauv, thiab tom qab ntawd tshawb pom OA ncua sijhawm xwm txheej ntawm nas. Cov txiaj ntsig pom tau hais tias qhov tsis muaj GRK2 ua rau qeeb qeeb ntawm OA, ua kom cov pob txha mos tsis zoo, ntau ntxiv thaj tsam ntawm cov pob txha tsis yog calcified, cov chondrocytes nrog matrix thiab kev qhia ntawm ovalbumin hauv pob txha mos. Lub caij no, nws ua rau GPCR cAMP teeb liab ntawm chondrocytes coj tus cwj pwm nquag thiab nrawm dua cov kev tsim dua tshiab ntawm kev ua lej sib txuas.
Paroxetine yog cov tshuaj pom zoo rau kho. Nws kuj tseem tuaj yeem ua ke nrog kev ua haujlwm ntawm GRK2 kom ruaj khov lub zog kinase, thiaj li ua rau phosphorylation thiab desensitization ntawm GPCR. Nws yog qhov tsis muaj txiaj ntsig GRK2 inhibitor. Cov kws tshawb nrhiav tau kwv yees tias cov tshuaj paroxetine tuaj yeem tiv thaiv GRK2 lossis qeeb qeeb ntawm OA. Tom qab siv cov paroxetine los kho OA cov nas, nws tau pom tias qhov inhibition ntawm GRK2 kev sib kho los ntawm paroxetine yog qhov txawv txav, uas txo qis pob txha mos tsis zoo, ib txwm ua rau cov ntsiab lus cAMP hauv chondrocytes, ua rau qeeb OA cov txheej txheem, thiab ua lub luag haujlwm hauv kev saib xyuas pob txha mos thiab matrix. kev tsim dua tshiab nyob rau tib lub sijhawm.
Tom qab ntawd, cov nyhuv ntawm paroxetine ntawm lub teeb liab pathological ntawm OA chondrocytes tau kawm ntxiv los ntawm kev ua yog tias txoj kev ntuag ntawm daim ntawv lo nyias nyias ovalbumin ntawm cov chondrocytes paub tab hauv thaj chaw tsis muaj calcified pob txha mos. Cov txiaj ntsig pom tau hais tias piv nrog kev tswj hwm, qhov hais tawm ntawm cov cim ntawm chondrocyte thinness hauv cov nas kho nrog paroxetine tau txo qis, thiab chondrocyte thinness tau qaug zog. Micro lub computer tomography (micro CT) kuj tau qhia tias paroxetine kev kho kom sib haum GRK2 inhibition tiv thaiv OA cov nas los ntawm pivot mineralization, subchondral pob txha kho thiab tsim pob txha pob txha.
Fadia Kamal, tus sau coj ntawm txoj kev tshawb no, hais tias lawv tab tom nrhiav kev pom zoo tias cov tshuaj no tuaj yeem siv hauv qhov kev sim tshiab rau kev kho tus mob txha caj qaum. Yog tias qhov kev sim no ua tiav, nws yuav pom qhov tsis muaj txiaj ntsig los daws qhov teeb meem qub ntawm osteoarthritis los ntawm pob txha mos rhuav thiab ploj.
