摘要
目的建立动脉粥样硬化血管性痴呆大鼠模型,从氧化应激反应中Nrf2-ARE蛋白通路入手,观察不同剂量五脏温阳化瘀汤对血管性痴呆的神经保护机制。方法制作动脉粥样硬化血管性痴呆大鼠模型,之后采用反复夹闭大鼠双侧颈总动脉方法制备血管性痴呆大鼠模型。术手后4周将大鼠随机分为假手术组、模型组、中低剂量组、中药中剂量组、中药高剂量组、脑复康组,之后灌胃给药,持续4周,进行Morris水迷宫行为学检测,观察各组大鼠空间学习及记忆能力,western blot检测大鼠海马区Nrf2蛋白细胞核与细胞浆内的表达,同时检测下游蛋白HO-1蛋白的表达。结果五脏温阳化瘀汤中剂量组和高剂量组从第3天开始可以明显缩短动脉粥样硬化血管性痴呆大鼠Morris水迷宫的逃避潜伏期,与假手术组\模型组比较P<0.01,有统计学差异。空间搜索实验中药中剂量组和高剂量组有效停留时间和有效停留距离明显延长,与假手术组\模型组比较P<0.05有统计学差异。动脉粥样硬化血管性痴呆大鼠海马区Nrf2-ARE通路被激活,Western blot检测显示五脏温阳化瘀汤可以使Nrf2蛋白由胞浆转移到胞核内,并激活下游蛋白HO-1,使其表达增强,nrf2蛋白胞浆内外的表达以及HO-1蛋白的表达各组与假手术组比较P<0.01,与模型组比较P<0.01,有统计学差异。结论五脏温阳化瘀汤能改善动脉粥样硬化血管性痴呆大鼠学习记忆能力,其作用机理可能与抑制动脉粥样硬化血管性痴呆大鼠的氧化应激反应,增强脑组织的抗氧化防御机制有关,其中剂量组和高剂量组作用显著。
Objective To establish a vascular dementia （VaD）model in rats based on atherosclerosis and To observe the treatment of vascular dementia rats with different doses of wu zang wen yang hua yu tang . Explore the mechanism of The decoction of wu zang wen yang hua yu tang from the aspects of oxidative stress response. Methods The rats in experimental groups were injected with a single dose of vitamin D（70U/kg）and loaded with high fat diet,The VaD model was established by repeatedly clipping the rat＇ s common carotid artery. Four weeks later, these rats were divided randomly into a sham-operated group, a sedentary control group, a low-doses group, a middle-dose group, a high-dose group, and a Piracetam treated group, the rats were administered orally by gastric intubation from the fourth week. Spatial learning and memory were assessed using the Morris water maze after the drug were given for 4 weeks. Following behavioral testing,The protein levels of the rats hippocampus Nff2 in the nucleus and cytoplasm and HO-I were examined in Western blotting. Results Beginning on day 3, the escape latencies in the Morris water maze of VD rats treated with High dose group and middle dose group were than the VD rats, compared with sham-operated group and sedentary control group P〈0. 01, which had Statistical differences. The rats treated by High dose with two kinds of dosage spent more time staying in the platform than rats with normal saline in the probe trials. The oxidative stress response of Nrf2-ARE pathway in VD rats＇hippocampus were induced. Western blot detection shows wu zang wen yang hua yu tang can remove Nff2 protein from cytoplasm to nucleus,and activate the HO-1 proteins,enhancing the proteins expression. The proteins expression of nrf2 which in thecytoplasm and thenucleus and HO-I, compared with sham-operated group and sedentary control group P〈0. 01,which had Statistical differences. Conclusion The decoction of wu zang wen yang hua yu tang can improve the cognitive impairment after Atherosclerosis and chronic cerebral hypoperfusion in rats, which may be related to prevent oxidative stress response and enhance the antioxidant mechanism. The high dosage and middle dosage have the significant effects.
出处
《云南中医学院学报》
2013年第3期8-11,20,共5页
Journal of Yunnan University of Traditional Chinese Medicine
基金
国家自然科学基金项目(NO:81160435)
关键词
动脉粥样硬化
血管性痴呆
五脏温阳
Nrf2蛋白通路
atheroselerosis
vaseular dementia
wu zang wen yang hua yu tang
Nrf2 pathway experimental studies
