淫羊藿苷通过促血管新生改善双侧颈总动脉结扎大鼠的学习记忆功能

Icariin improves learning and memory via promoting angiogenesis in bilateral common carotid artery occlusion rats

目的探究淫羊藿苷(Ica)对双侧颈总动脉结扎(BCCAO)大鼠学习记忆功能及脑内血管新生的影响。方法雄性SD大鼠随机分为假手术组,模型组和Ica 15、30、60 mg·kg^(-1)组,造模后第10日开始灌胃,每日1次,连续2周。Morris水迷宫检测行为学能力;CD31标记脑微血管;Griess法测一氧化氮(NO)含量;Western blot检测血管内皮生长因子A(VEGFA)及其受体2(VEGFR2)、基质金属蛋白9(MMP9)、细胞外信号调节激酶1/2(ERK1/2)和内皮型一氧化氮合酶(eNOS)蛋白量及磷酸化水平。结果 Ica改善BCCAO大鼠空间学习记忆能力,第4日和第5日定位航行逃避潜伏期明显缩短,空间探索实验中大鼠穿越原平台区域的次数明显增加(P<0.05);增加脑内血管数量(P<0.05),提高大脑皮质NO含量(P<0.05),增加脑组织中VEGFA、VEGFR2、MMP9蛋白表达及ERK1/2和e NOS蛋白磷酸化水平(P<0.05)。结论 Ica可通过增加脑内微血管新生而改善BCCAO大鼠学习记忆的功能。

AIM To explore the effects of icariin（ Ica） on learning and memory impairments and angiogenesis in bilateral common carotid artery occlusion（ BCCAO） rats. METHODS Male Sprague Dawley rats were randomly divided into sham group, BCCAO group, and Ica 15, 30, 60 mg·kg^（-1） group. Administrated with Ica or distilled water daily from the 10 th day after BCCAO for 2 weeks. Morris water maze was used to test behavioral function; CD31 antibody was used to label microvessels; nitric oxide（ NO） content in cortex was tested by Griess method; the protein expression of vascular endothelial growth factor A（ VEGFA）, vascular endothelial growth factor receptor 2（VEGFR2）, matrix metalloproteinase 9（MMP9）, and the phosphorylation of extracellular signal- regulated kinase 1/2（ERK1/2） and endothelial nitric oxide synthase（e NOS） were assayed by Western blot. RESULTS Ica treatment significantly improved the learning and memory function of BCCAO rats： the escape latency of space navigation test in day 4 and day 5 was significant shorter（P〈 0.05） and the number of crossing platform region of spatial exploring test was increased（ P 〈0.05）. Ica treatment increased microvessel density（P〈 0.05）, elevated the content of NO in rat＇s cerebral cortex, and enhanced the protein expression of VEGFA, VEGFR2, MMP 9 and the phosphorylation of ERK1/2 and eNOS proteins（all P〈 0.05）.CONCLUSION Ica improves the function of learning and memory of BCCAO rats via promoting angiogenesis in cortex.