健脑补肾口服液通过cGAS/STING通路抑制氧化应激改善阿尔茨海默病小鼠认知功能的研究OA

Objective To investigate whether Jiannao Bushen Oral Liquid(健脑补肾口服液,JBOL)ameliorates cognitive function in an Alzheimer's disease(AD)mouse model by inhibiting oxidative stress via the cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS/STING)pathway.Methods Thirty 6-month-old male senescence-accelerated mouse prone 8(SAMP8)mice were ran-domly divided into a model group,a donepezil group(0.65 mg/kg),and a JNBSL group(0.9 g/kg).Ten age-matched senescence-accelerated mouse resistant 1(SAMR1)mice served as the normal control.All groups received daily intragastric administration for 90 consecutive days.Cognitive and exploratory behaviors were evaluated using the Morris water maze and open field tests.Cerebral amy-loid-β(Aβ)deposition and cGAS protein expression were detected by immunofluorescence(IF).Hippocampal mitochondrial morphol-ogy was observed via transmission electron microscopy(TEM).The protein expression levels of cGAS and STING were analyzed by Western blot(WB).The activities of glutathione peroxidase(GSH-Px),superoxide dismutase(SOD),and catalase(CAT),as well as the levels of malondialdehyde(MDA),8-hydroxy-2'-deoxyguanosine(8-OHdG),and 3-nitrotyrosine(3-NT),were measured in hip-pocampal tissue.Results Compared with the model group,the JNBSL-treated mice showed significantly improved cognitive function(P<0.05,P<0.01),reduced hippocampal Aβ deposition(P<0.01),ameliorated mitochondrial morphology,downregulated cGAS and STING protein expression(P<0.0001),increased activities of GSH-Px,SOD,and CAT(P<0.05),and decreased levels of MDA,8-OHdG,and 3-NT(P<0.05,P<0.01).Conclusion JBOL can inhibit oxidative stress via the cGAS/STING pathway,thereby alleviating AD-like pathological damage and improving cognitive function in AD mice.