目的观察淫羊藿苷(ICA)抗慢性脑低灌注大鼠模型学习记忆减退的可能机制。方法雄性SD大鼠随机分为假手术组、模型组、低、高剂量ICA治疗组(n=15)。双侧颈总动脉结扎(BCCAO)建立慢性脑低灌注模型,低、高剂量ICA治疗组造模后第10天分别每日灌胃ICA10、40 mg/kg,连续灌胃23d。制模后第28天后Morris水迷宫检测大鼠空间学习记忆功能,处死大鼠,Western blot法分别检测海马过氧化物酶体增殖物激活型受体α(PPARα)和过氧化物酶体增殖物激活受体γ共激活因子-1α(PGC-1α)的蛋白表达。结果定位航行实验中,模型组大鼠运动距离较假手术组明显增加,而给予ICA低、高剂量组大鼠运动距离较模型组减少(P〈0.01,P〈0.05)。空间探索实验中,模型组大鼠目标象限停留时间较假手术组明显减少,而给予ICA低、高剂量组大鼠在目标象限停留时间较模型组明显延长(P均〈0.05)。而且,模型组大鼠海马PPARα和PGC-1α蛋白表达均明显下降,而ICA低、高剂量能明显增加其表达(P〈0.01,P〈0.05)。结论 ICA可改善慢性脑低灌注大鼠模型的空间学习记忆减退,其机制至少与其上调大鼠海马PPARα和PGC-1α蛋白表达有关。
Objective This study was to observe the potential mechanisms of icariin on chronic cerebral hypoperfusion rats. Methods Male SD rats were randomly divided into sham operation group,model group,icariin low and high dose group intervention model group( n = 15 in each group). The chronic cerebral hypoperfusion model was induced by permanent occlusion of the common carotid arteries( BCCAO). Low- and high- dose group were administered by icariin at doses of 10,40 mg / kg by gavage on 10 th day after BCCAO for 23 days.Morris water maze was used to test the rat spatial learning and memory ability on 28 th day. Western blot assay was used to detect the protein expressions of peroxisome- proliferator- activated receptors α( PPARα) and peroxisome- proliferator- activated receptors γ coactivator- 1α( PGC- 1α) after the rats were sacrificed. Results In the place navigation tests,the swimming distances in model rats were obviously longer than those in sham group,while icariin administration at doses of 10,40 mg / kg more significantly shortened the swimming distances than those in model rats( P〈0. 01,P〈0. 05). In the probe trial assay,the time of crossing over the hidden location of the former platform in model rats was significantly shorter compared with sham group,and icariin- treated groups were significantly longer compared with the model group( P〈0. 05). Moreover,icariin treatment significantly increased BCCAO- induced decrease in protein expressions of PPARα and PGC- 1α( P〈0. 01,P〈0. 05). Conclusion Icariin can improve spatial learning and memory in chronic cerebral hypoperfusion rats. The possible mechanism,at least in part,was due to upregulating the expressions of PPARα and PGC- 1α protein in rat hippocampi.