间断性常压低氧后适应对慢性脑血流低灌注大鼠脑白质损伤和认知功能障碍的影响

摘要

Objective To study the effect of intermittent normobaric hypoxia postconditioning (INHP) on brain white matter lesion and cognitive impairment due to chronic cerebral hypoperfu -sion in rats .Methods Thirty-two SD rats were divided into sham group ,model group,INHP1 group and INHP2 group (8 in each group) .Cognitive function of rats was assessed by Morris water maze test and severity of brain white matter lesion was assessed with Klüver-Barrera staining . Astroglia and microglia in brain white matter were marked with GFAP and Iba-1 antibodies .Results The cognitive impairment ,axonal loss and vacuolization in brain white matter with activated astrocytes and microglias occurred earlier in model group than in sham group .The reference anamness was poorer ,the brain white matter lesion was severer ,and the number of GFAP-posi-tive astrocytes and Iba-1-positive microglias was greater in INHP1 group than in model group , whereas the reference anamness was better ,the brain white matter lesion was milder ,and the number of GFAP-positive astrocytes and Iba-1-positive microglias was smaller in INHP2 group than in model group (P<0 .05) .Conclusion Delayed INHP but not early INHP can improve cognitive impairment and brain white matter lesion due to chronic cerebral hypoperfusion .%目的 探讨间断性常压低氧后适应(intermittent normobaric hypoxia postconditionning,INHP)对慢性脑血流低灌注大鼠脑白质损伤和认知功能障碍的影响.方法 选择健康成年雄性SD大鼠32只,随机分为假手术组、模型组、INHP1组和INHP2组,每组8只.Morris水迷宫用于评价大鼠的认知功能,Klüver-Barrera 染色用于评价脑白质损伤的严重程度,胶质纤维酸性蛋白(GFAP)抗体、Iba-1抗体分别用于免疫标记脑白质中星形胶质细胞和小胶质细胞.结果 与假手术组比较,模型组大鼠出现认知功能障碍、脑白质中髓鞘脱失、空泡形成,并有星形胶质细胞、小胶质细胞活化;与模型组比较,INHP1组大鼠参考记忆力较差、脑白质损伤较重,脑白质中GFAP阳性星形胶质细胞、Iba-1阳性小胶质细胞较多(P<0.05),而INHP2组大鼠参考记忆力较好、脑白质损伤较轻,脑白质中GFAP阳性星形胶质细胞、Iba-1阳性小胶质细胞较少(P<0.05).结论 延迟INHP可改善慢性脑血流低灌注导致的认知功能障碍和脑白质损伤,而早期INHP是有害的.