葡萄籽原花青素减轻孕期应激大鼠子代的星形胶质细胞损伤OA

Objective To investigate the effects of grape seed proanthocyanidins on hippocampal astrocyte and cognitive performance in the offsprings of SD rats exposed to prenatal stress.Methods Pregnant SD rats were randomized into control group,stress group,and grape seed proanthocyanidin(GSP)group.At gestational days 15-20,the prenatal rats subjected to restraint stress three times per day in a transparent plastic container that restricted movement for 45 min per session in stress group and GSP group.Based on this,the dam from GD15 to postnatal day 20(PD20)and the offsprings from PD21-60 in GSP group were given orally GSP 200 mg/(kg·d).The rats in control group were fed normally.At PD60,the open-field,elevated plus-maze,and Y-maze tests were used to evaluate cognitive performance in offsprings.Hippocampal astrocytic morphology and density were assessed by immunohistochemistry and immunofluores-cence.The mRNA levels of pro-inflammatory cytokines IL-1β,IL-6,and TNF-α were detected in hippocampus of offsprings by qRT-PCR,while the protein expressions of astrocyte marker(GFAP)and NF-κB were determined by Western blot.Results Compared with control group,total locomotor distance and central zone distance in the open-field test significantly decreased in offsprings in stress group(P<0.01),the percentages of time spent in and entries into the open arms also decreased in the elevated plus-maze test(P<0.001),and the percentages of total locomotion time and distance spent in the novel arm in the Y-maze test decreased(P<0.01).In GSP group,the behavioral deficits induced by stress were significantly ameliorated(P<0.05).The mRNA levels of IL-1β,IL-6,and TNF-α in hippocampus in stress group were significantly higher than in control group(P<0.001);these levels were significantly lower in GSP group than in stress group(P<0.05).Immunohistochemical and immunofluorescent results showed that PS offspring exhibited the reduction of astrocytic density,smaller somata,and shorter processes in the hippocampus compared with controls;GSP restored astrocytic density and normalized morphology.Compared with control group,hippocampal GFAP level significantly reduced in offsprings(P<0.01),and NF-κB expression significantly increased(P<0.001);compared with stress group,hipopocampal GFAP level significantly increased in GSP group(P<0.05),and NF-κB protein expression decreased(P<0.01).Conclusion Grape seed proanthocyanidins may alleviate PS-induced hippocampal astrocytic damage and protect cognitive function of the offsprings by inhibit-ing the NF-κB signaling pathway.