蛇床子素减轻脂多糖诱导的大鼠学习记忆减退

目的观察蛇床子素对脂多糖诱导的大鼠学习记忆减退的作用,并初探其可能的作用机制。方法 40只雄性SD大鼠随机分为假手术组、模型组、阳性药组及蛇床子素组。阳性药组、蛇床子素组分别每日1次灌胃布洛芬、蛇床子素40 mg.kg-1,连续12 d,假手术组、模型组灌胃等体积的生理盐水,3 d后侧脑室注射脂多糖诱导大鼠的神经炎症模型,制模后d 5开始Morris水迷宫检测大鼠的空间记忆能力,连续5 d。Morris水迷宫检测结束后,处死大鼠,HE染色观察大鼠海马神经元损伤情况,real time RT-PCR法测定海马肿瘤坏死因子α(Tnf-α)、白细胞介素-1β(Il-1β)、诱导型一氧化氮合酶(Nos2)及环氧合酶-2(Cox-2)的mRNA表达。结果侧脑室注射脂多糖后,大鼠在定向航行实验中的逃避潜伏期显著增加(P<0.05),空间探索实验中的校正逃避潜伏期缩短(P<0.05),海马神经元明显受损,且海马Tnf-α、Il-1β、Nos2及Cox-2的mRNA表达增加(P<0.05);然而,蛇床子素及布洛芬明显缩短了大鼠的定向航行实验中的逃避潜伏期(P<0.05),延长了空间探索实验中的校正逃避潜伏期(P<0.05),减轻了海马神经元损伤,且降低海马Tnf-α、Il-1β、Nos2及Cox-2的mRNA表达。结论蛇床子素可减轻脂多糖诱导的大鼠学习记忆减退及海马神经元损伤,其机制与抑制炎症相关基因的mRNA表达有关。

Osthole attenuates learning and memory deficits induced by lipopolysaccharide in rats

AIM To investigate the protective effect of osthole on learning and memory deficits induced by lipopolysaccharide(LPS)in rats,and explore its possible mechanisms.METHODS Forty male Sprague Dawley rats were randomly divided into sham,model,positive-and osthole-prevented groups.Positive-and osthole-prevented groups were administrated with ibuprofen or osthole at doses of 40 mg·kg-1 once daily by gavage consecutive for 12 d,while the sham and model groups were administrated with volume-matched normal saline by gavage,instead.After having prevented for 3 d,rat model with neuro-inflammation was induced by injection of LPS to lateral cerebral ventricle.And 5 d later after model establishment,the ability of learning and memory of rats was tested by Morris water maze continuously for 5 days.All the rats were sacrificed after Morris water maze test,and neuronal injury in hippocampus was observed by hematoxylin-eosin staining,and the mRNA expres-sions of Tnf-α,Il-1β,Nos2 and Cox-2 were detected by RT-PCR in hippocampus,respectively.RESULTS Injection of LPS to lateral cerebral ventricle significantly increased escape latency in the place navigation test,and decreased adjusted escape latency in spatial probe test(P < 0.05).Meanwhile,LPS injection caused neuronal injury in hippocampus,and increased the mRNA expressions of Tnf-α,Il-1β,Nos2 and Cox-2 in rat hippocampus(P < 0.05).However,prevention with ibuprofen or osthole significantly shortened escape latency in the place navigation test,and increased adjusted escape latency in spatial probe test,and attenuated neuronal injury in hippocampus(P < 0.05).Furthermore,prevention with ibuprofen or osthole significantly decreased the mRNA expressions of Tnf-α,Il-1β,Nos2 and Cox-2 in rat hippocampus(P < 0.05).CONCLUSION Osthole may attenuate spatial learning and memory deficits and neuronal injury induced by LPS in rats.The mechanisms are,at least partly,due to the inhibition of the mRNA expressions of inflammation-related genes.