Zogulitsa

Sigma receptor 1 (σR1) ndi mapuloteni omwe si opioid transmembrane omwe amatha kukhala ngati molecular chaperone pa endoplasmic reticulum-mitochondrial membrane.Ma Ligand a σR1, monga (+)-pentazocine [(+)-PTZ], amapereka chizindikiro cha retinal neuroprotection mu vivo ndi mu vitro.Posachedwapa tidasanthula za retinal phenotype ya mbewa zomwe zikusowa σR1 (σR1 KO) ndikuwona momwe retina imayendera komanso kugwira ntchito kwa mbewa zazing'ono (masabata a 5-30) koma kuchepetsedwa kwa mayankho olakwika (nSTRs), kutayika kwa retinal ganglion cell (RGC), ndi kusokoneza. za optic nerve axon zomwe zimagwirizana ndi kukanika kwamkati kwa retina pofika chaka chimodzi.Deta iyi idatipangitsa kuyesa lingaliro lakuti σR1 ikhoza kukhala yovuta popewa kupsinjika kwa retina kwanthawi yayitali;Kuti mudziwe ngati σR1 ikufunika (+) -PTZ neuroprotective zotsatira, ma RGC otalikirana ndi mtundu wakutchire (WT) ndi σR1 KO mbewa adawonetsedwa ndi xanthine-xanthine oxidase (10 µM: 2 mU/ml) kuti apangitse kupsinjika kwa okosijeni pamaso kapena kusakhalapo kwa (+) -PTZ.Kufa kwa maselo kunayesedwa ndi kusanthula kwa terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).Kuti muwone zotsatira za kupsinjika kwanthawi yayitali pa ntchito ya RGC, matenda a shuga adayambitsidwa mu 3-sabata C57BL/6 (WT) ndi σR1 KO mbewa, pogwiritsa ntchito streptozotocin kuti apereke magulu anayi: WT nondiabetic (WT non-DB), WT Diabetic (WT-DB) ), σR1 KO non-DB, ndi σR1 KO-DB.Pambuyo pa masabata a 12 a shuga, pamene mbewa zinali ndi masabata a 15, kupanikizika kwa intraocular (IOP) kunalembedwa, kuyesa kwa electrophysiologic (kuphatikizapo kuzindikira nSTRs), ndipo chiwerengero cha RGCs chinawerengedwa m'magawo a retinal histological. (+)-PTZ sinathe kuletsa kufa kwa ma RGC obwera chifukwa cha kupsinjika kwa okosijeni omwe amakololedwa ku mbewa za σR1 KO koma idapereka chitetezo champhamvu ku imfa ya ma RGC otengedwa kuchokera ku mbewa za WT.Pakufufuza kwa kupsinjika kwanthawi yayitali komwe kumabwera chifukwa cha matenda a shuga, IOP yoyezedwa m'magulu anayi a mbewa inali mkati mwanthawi zonse;komabe, panali kuwonjezeka kwakukulu kwa IOP ya σR1 KO-DB mbewa (16 ± 0.5 mmH g) poyerekeza ndi magulu ena oyesedwa (σR1 KO non-DB, WT non-DB, WT-DB: ~12 ± 0.6 mmHg ).Ponena za kuyesa kwa electrophysiologic, nSTRs ya σR1 KO mbewa zopanda DB zinali zofanana ndi mbewa za WT zopanda DB pa masabata a 15;komabe, anali otsika kwambiri mu σR1 KO-DB mbewa (5 ± 1 µV) poyerekeza ndi magulu ena, kuphatikiza, makamaka, σR1 KO-nonDB (12±2 µV).Monga momwe zimayembekezeredwa, chiwerengero cha RGCs mu σR1 KO mbewa zopanda DB chinali chofanana ndi mbewa za WT zosakhala za DB pa masabata a 15, koma pansi pa kupsinjika maganizo kwa matenda a shuga panali ma RGC ochepa mu retinas a σR1 KO-DB mbewa.Ili ndilo lipoti loyamba kusonyeza mosakayikira kuti zotsatira za neuroprotective za (+) -PTZ zimafuna σR1.σR1 KO mbewa zimawonetsa mawonekedwe abwinobwino a retina ndikugwira ntchito ali achichepere;komabe, mukakumana ndi zovuta za matenda a shuga, pamakhala kuchepa kwa magwiridwe antchito a retina mu mbewa za σR1 KO kotero kuti kusagwira ntchito kwa ganglion kumawonedwa paubwana kwambiri kuposa mbewa zopanda matenda a shuga σR1 KO.Deta imathandizira lingaliro loti σR1 imagwira ntchito yofunika kwambiri pakuchepetsa kupsinjika kwa retina ndipo ikhoza kukhala chandamale chofunikira cha matenda a retina.