摘要
目的:探讨不同剂量大豆异黄酮(SIF)对β淀粉样蛋白(Aβ)介导的大鼠行为学及抗氧化能力的影响。方法:60只健康雄性SD大鼠随机分为假手术组、模型组、SIF低、中、高剂量组和阳性对照组,每组10只。SIF组按规定剂量灌胃给药,阳性对照组给予维生素E,假手术组和模型组灌胃等量的0.5%羧甲基纤维素钠(CMC-Na)。连续灌胃14d后,模型组和实验组大鼠双侧海马CA1区注射Aβ25-35,假手术组注射等量生理盐水,于术后7d,Morris水迷宫实验检测大鼠学习记忆能力,之后处死大鼠,观察病理形态学改变及检测血清和脑组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧物酶(GSH-Px)、丙二醛(MDA)等抗氧化指标的水平。结果:与模型组比较,SIF各剂量组和阳性对照组平均逃避潜伏期缩短,穿越站台所在位置的次数增多(P<0.05),SIF中、高剂量组较阳性对照组潜伏期缩短明显(P<0.05)。免疫组化结果显示,与模型组比较,SIF各剂量组和阳性对照组可减少海马区Aβ25-35免疫反应阳性产物的表达,SIF高剂量组较阳性对照组减少明显(P<0.05)。与模型组比较,SIF中、高剂量组及阳性对照组大鼠血清和脑组织SOD和GSH-Px活性不同程度增加,MDA含量不同程度降低(P<0.05);SIF高剂量组在提高大鼠血清和脑组织SOD活性及降低MDA含量方面优于阳性对照组(P<0.05);SIF高剂量组提高大鼠血清中GSH-Px活性较阳性对照组明显(P<0.05),对脑组织中GSH-Px活性的影响与阳性对照组相比无统计学差异(P>0.05)。结论:SIF能改善Aβ25-35所致阿尔茨海默病模型大鼠的行为能力,可能是通过改善机体氧化还原状态,提高抗氧化水平,由此发挥其神经保护作用。
AIM：To study the effects of different doses of soybean isoflavone（SIF） on ethology and antioxidative potential of AD model rats.METHODS：Sixty healthy male SD rats were randomly divided into sham operation group;model group;low,medium,high dose SIF groups and positive control group,respectively,with each group including 10 rats.The regulated dose medicine was given to the SIF groups and positive control group by intragastric administration daily for 14 days before Aβ injection,sham operation group and model group were given equivalent of 0.5% CMC-Na.Morris water maze experiment was adopted to evaluate the learning and memory ability of rats in each group on the 7th day after Aβ injection,then the pathological change in rats＇ hippocampus was measured by immunohistochemical method,and the activities or levels of SOD,GSH-Px,MDA in serum and brain tissue were determined.RESULTS：Comparing with model group,the mean escape latencies of rats were shortened and number of times that passed through original platform location increased in every dose SIF groups and positive control group（P0.05）,the mean escape latencies of rats in medium and high dose SIF groups were significantly shortened than that of positive control group（P0.05）.Result of immunohistochemistry revealed：comparing with model group,the integrated optical density of Aβ positive reaction product in every dose SIF groups and positive control group was decreased,and the Aβ-positive expression in high dose SIF group was significantly decreased than that of positive control group（P0.05）.Comparing with model group,the activities of SOD and GSH-Px in serum and brain tissue in medium and high dose SIF groups and positive control group were increased differently,and the content of MDA was decreased differently（P0.05）;The activity of SOD in serum and brain tissue in high dose SIF group was much higher than that of positive control group,and the content of MDA in high dose SIF group was much lower than that of positive control group（P0.05）;The activity of GSH-Px in serum in high dose SIF group was much higher than that of positive control group,but the activity of GSH-Px in brain tissue in high dose SIF group was no significant difference compared with positive control group（P0.05）.CONCLUSION：SIF could improve the behavioral capacity of AD model rats induced by Aβ25-35,and the probable mechanism is that SIF changed the redox state,then increased the antioxidative level,thereby exhibited its neuro-protective effects.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2010年第10期1122-1127,共6页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
浙江省卫生厅科技计划项目(2006B103)
温州市科技局科技计划项目(Y20090116)
