槲皮素对缺氧缺血性脑损伤新生大鼠远期学习记忆及PARP-1/AIF信号通路的影响  

The effect of Quercetin on the long-term memory and PARP- 1 /AIF signal path in neonatal rats with hypoxicischemic brain damage

作　　者：杨青丽[1,2] 陈彦锋[2] YANG Qingli;CHEN Yanfeng(NICU, Luohe Central Hospital;Department of Basic Medical Sciences, Luohe Medical College, Luohe 462000 , Henan, China)

机构地区：[1]漯河市中心医院NICU [2]漯河医学高等专科学校基础医学部,河南漯河462000

出　　处：《临床儿科杂志》2016年第12期936-941,共6页Journal of Clinical Pediatrics

摘　　要：目的观察槲皮素对缺氧缺血性脑损伤(HIBD)新生大鼠远期学习记忆及多聚二磷酸腺苷核糖聚合酶-1(PARP-1)/凋亡诱导因子(AIF)信号通路的影响。方法 56只7日龄新生SD大鼠随机分为假手术组、HIBD组、槲皮素低剂量(20 mg/kg)组和槲皮素高剂量(40 mg/kg)组,每组14只。除假手术组外,其余各组经右颈总动脉结扎并缺氧制作HIBD模型。槲皮素组在造模后立即腹腔注射相应剂量的槲皮素,每日1次,连续7 d;假手术组和HIBD组分别在同一时间点给予等量生理盐水腹腔注射。21日龄时,各组大鼠行悬挂实验和滑棒实验检测神经功能,28日龄时各组大鼠行Morris水迷宫检测空间学习记忆能力。水迷宫实验结束后,大鼠断头取脑,苏木精-伊红(HE)染色观察海马病理学改变,Western blot法检测海马PARP-1和AIF表达情况,ELISA法检测海马Bcl-2和Bax表达情况。结果与假手术组比较,HIBD组的神经功能和学习记忆能力显著下降;而与HIBD组比较,槲皮素低、高剂量组的神经功能和空间学习记忆能力显著提高,差异均有统计学意义(P<0.05)。HE染色显示,假手术组大鼠海马的神经元结构完整,排列整齐紧密;HIBD组海马的神经元数量明显减少,且排列疏松;槲皮素低、高剂量组则较HIBD组神经元数量明显增多。HIBD组大鼠海马PARP-1、AIF和Bax表达高于槲皮素低、高剂量组,而槲皮素低、高剂量组高于假手术组,Bcl-2的变化则与此相反,差异均有统计学意义(P<0.05)。槲皮素低、高剂量组相比,神经功能、学习记忆能力以及PARP-1、AIF、Bcl-2和Bax的表达差异均无统计学意义(P>0.05)。结论槲皮素可以改善HIBD新生大鼠的远期学习记忆能力,其机制可能通过下调PARP-1/AIF细胞凋亡信号通路,抑制神经细胞凋亡,发挥脑保护作用。Objective To explore the effect of Quercetin on the long-term memory and PARP-1 /AIF signal path in neonatal rats with hypoxic-ischemic brain damage (HIBD). Methods Fifty-six 7 -day-old SD rats were randomly divided into sham-operation group, HIBD group, low dose of Quercetin group ( 20 mg/kg), and high dose of Quercetin group ( 40 mg/kg),each of 14 rats. Except for sham-operation group, in the other groups HIBD model were made by right common carotid arter yligation and anoxiate. The Quercetin groups were injected with the corresponding doses of Quercetin immediately once a daycontinuously for 7 days after the model was made,. Sham-operation group and HIBD group were intraperitoneally injected withnormal saline at the same time. Neural function was evaluated by Hanging wire test and Vertical pole test at 21 days old. Thecapacity of learning and memory was detected by Morris water maze at 28 days old, and then rats were killed and brains weretaken. HE was used to observe the pathological changes of hippocampus. Western blot were used to detect the expression ofPARP-1 and AIF in hippocampus. Results Compared with sham-operation group, the neural function and learning and memoryability decreased significantly in HIBD group. Those ability in both low dose and high dose of Quercetin groups were remarkablyincreased in comparison with HIBD group, and there were statistic differences (P < 0 . 05 ). HE showed an neuro-structure wasintact and neatly arranged in hippocampus in sham-operation group. The neurons in HIBD group were obviously decreased innumber and loosely arranged while those in both low dose and high dose of Quercetin groups were more increased and neatly arranged when compared with HIBD group. The expressions of PARP-1 , AIF, and Bax in rats’ hippocampus were higher inHIBD group than those in low dose or high dose of Quercetin groups which were higher than those in sham-operation group. The change of Bcl- 2 was the opposite, and there were statistic differences (P < 0 . 05 ). Furthermore, there was no dif

关 键 词：缺氧缺血性脑损伤 槲皮素 PARP-1/AIF信号通路 学习记忆 大鼠 

分 类 号：R742[医药卫生—神经病学与精神病学]