柚皮素对阿尔茨海默病模型大鼠学习记忆能力的影响

Effect of Naringenin on Learning and Memory Ability on Model Rats with Alzheimer Disease

目的:探讨柚皮素对阿尔茨海默病(AD)模型大鼠学习记忆能力的影响。方法:将30只雄性SD大鼠随机分为假手术组、模型组、柚皮素组。侧脑室注射链脲佐菌素(ICV-STZ)(3 mg/kg,共2次)制备AD模型。柚皮素组行柚皮素灌胃,其余两组生理盐水灌胃,1次/d,连续3 w。以Morris水迷宫测试各组大鼠学习记忆能力;测试完成后取各组大鼠脑组织,用化学比色法测定其超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量;免疫组织化学染色法观察其Aβ42和Aβ40的表达情况;Western blotting法定量检测其Tau蛋白的表达及磷酸化程度。结果:水迷宫结果显示,与假手术组比较,模型组平均逃避潜伏期显著延长(P<0.05),在原平台活动时间显著缩短(P<0.05);与模型组比较,柚皮素组平均逃避潜伏期显著缩短(P<0.05),在原平台活动时间显著延长(P<0.05);化学比色法结果显示,模型组较假手术组肠组织SOD活性显著降低(P<0.05);而柚皮素组较模型组肠组织SOD活性显著升高(P<0.05);与假手术组比较,模型组肠组织MDA含量显著升高(P<0.05);与模型组比较,柚皮素组MDA含量显著降低(P<0.05);免疫组化结果显示,模型组Aβ40、Aβ42阳性表达较对照组显著增多(P<0.05),柚皮素组较模型组阳性表达显著降低(P<0.05);Tau蛋白表达在各组间无差异,但模型组Tau蛋白磷酸化程度较对照组显著增强(P<0.05),柚皮素组较模型组显著减弱(P<0.05)。结论:柚皮素可通过氧化应激途径较好地改善阿尔茨海默病模型大鼠的学习记忆能力。

Objective：To investigate the effects of naringenin on the learning and memory ability of Alzheimer disease（AD）rats.Methods：30 male SD rats were randomly divided into control group（sham operation group）,model group and naringenin group.AD model was established by injecting strepoztocin（3mg/kg） twice into each of two intracerebroventriculas.Naringenin group were given intragastric administration of naringenin once a day for 3 weeks and the other two groups were given intragadtric administration of normal saline with the same dosage and time period.After 3 weeks,learning and memory ability in all the three groups were analyzed by Morris water maze,the activity of superoxide dismutase（SOD）and the content of malondialdehyde（MDA） of the rats′brain tissue was detected by chemical colorimetric determination.Observed the expressions of Aβ42 and Aβ40 by immunohistochemical method.The expression and degree of phosphorylation of tau protein was assayed by western blotting.Results：1.Compared with the sham operation group,the mean escape latency of the model group was significantly prolonged（P0.05）and the time that rats were in the platform quadrant was significantly shortened（P0.0.5）.On the contrary,compared with the model group,the mean escape latency of naringenin group was significantly shortened（P0.05）and the time that rats were in the platform quadrant was significantly extended（P0.005）.2.The level of MDA in the model group,compared with the sham operation group group,was significantly increased（P0.05）.Whereas,that of naringenin group,compared with the model group,was significantly decreased compared with the sham operation group（P0.05）.The activity of SOD in the naringenin group was significantly increased comparing with the model group（P0.05）.3.The expressions of Aβ40and Aβ42 in model group were obviously up-regulated.Instead,the expressions of Aβ40and Aβ42 in the naringenin group were significantly down regulated.4.There was no significant difference in the expression of tau protein among each groups.Nevertheless,the phosphorylation of tau protein in the model group was significantly enhanced than that in the control group（P0.05）,and the phosphorylation of tau protein in the naringenin group was significantly reduced than that in the model group（P0.05）.Conclusion：Naringenin can improve learning and memory ability of model rats with Alzheimer disease through the approach of oxidative stress.