Kayayyaki

Sigma receptor 1 (σR1) shine furotin transmembrane ba-opioid wanda zai iya aiki azaman chaperone na kwayoyin halitta a cikin endoplasmic reticulum-mitochondrial membrane.Ligands don σR1, irin su (+) -pentazocine [(+) -PTZ], suna ba da alamar kariya ta retina a cikin vivo da in vitro.Kwanan nan mun bincika nau'in nau'in ƙwayar cuta na berayen da ba su da σR1 (σR1 KO) kuma mun lura da ilimin halittar jiki na al'ada da aiki a cikin ƙananan mice (makonni 5-30) amma raguwa mara kyau na ƙofa (nSTRs), asarar ganglion cell (RGC), da rushewa. na axon na jijiyar gani daidai da rashin aikin ido na ciki da shekara 1.Waɗannan bayanan sun sa mu gwada hasashen cewa σR1 na iya zama mai mahimmanci don hana damuwa na retinal na yau da kullun;An yi amfani da ciwon sukari a matsayin samfurin damuwa na yau da kullum.Don sanin ko σR1 yana buƙatar (+) - PTZ neuroprotective effects, RGCs na farko da aka ware daga nau'in daji (WT) da σR1 KO mice an fallasa su zuwa xanthine-xanthine oxidase (10 µM: 2 mU / ml) don haifar da damuwa na oxidative a gaban ko rashi (+) -PTZ.An kimanta mutuwar kwayar cutar ta hanyar bincike na deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).Don tantance tasirin danniya na yau da kullun akan aikin RGC, an haifar da ciwon sukari a cikin 3-week C57BL/6 (WT) da σR1 KO mice, ta amfani da streptozotocin don samar da ƙungiyoyi huɗu: WT marasa ciwon sukari (WT ba DB), WT masu ciwon sukari (WT-DB). σR1 KO wadanda ba DB, da σR1 KO-DB.Bayan makonni 12 na ciwon sukari, lokacin da mice ke da makonni 15, an rubuta matsa lamba na intraocular (IOP), an yi gwajin electrophysiologic (ciki har da gano nSTRs), kuma an ƙidaya adadin RGC a cikin sassan histological na retinal. In vitro binciken ya nuna cewa (+) -PTZ ba zai iya hana mutuwar danniya da ke haifar da mutuwar RGCs da aka girbe daga berayen σR1 KO amma sun ba da kariya mai ƙarfi daga mutuwar RGCs da aka girbe daga mice WT.A cikin nazarin damuwa na yau da kullum da ciwon sukari ya haifar, IOP da aka auna a cikin ƙungiyoyin linzamin kwamfuta guda hudu yana cikin kewayon al'ada;duk da haka, an sami karuwa mai yawa a cikin IOP na σR1 KO-DB mice (16 ± 0.5 mmH g) idan aka kwatanta da sauran kungiyoyin da aka gwada (σR1 KO wadanda ba DB, WT ba DB, WT-DB: ~ 12 ± 0.6 mmHg ).Game da gwajin electrophysiologic, nSTRs na σR1 KO mice marasa DB sunyi kama da WT wadanda ba DB ba a makonni 15;duk da haka, sun kasance ƙananan ƙananan a cikin σR1 KO-DB mice (5 ± 1 µV) idan aka kwatanta da sauran kungiyoyi, ciki har da, musamman, σR1 KO-nonDB (12 ± 2 µV).Kamar yadda aka zata, adadin RGCs a cikin σR1 KO wadanda ba DB mice ba sun yi kama da WT wadanda ba DB ba a makonni 15, amma a karkashin damuwa mai tsanani na ciwon sukari akwai ƙananan RGCs a cikin retina na σR1 KO-DB mice.Wannan shine rahoton farko. yana nuna babu shakka cewa tasirin neuroprotective na (+) -PTZ yana buƙatar σR1.σR1 KO mice suna nuna tsarin tsarin ido na al'ada da aiki a lokacin ƙuruciya;duk da haka, lokacin da aka fuskanci damuwa na ciwon sukari na yau da kullum, akwai hanzari na raguwa na aikin retinal a cikin σR1 KO mice irin wannan rashin aikin ganglion cell yana lura da shi a farkon shekaru fiye da marasa ciwon sukari σR1 KO mice.Bayanan sun goyi bayan hasashe cewa σR1 yana taka muhimmiyar rawa a cikin yanayin damuwa na retinal kuma yana iya zama muhimmiyar manufa don cutar ciwon ido.