摘要
目的观察姜黄素对阿尔茨海默病(AD)大鼠学习记忆能力的改善,以了解其对AD大鼠学习记忆能力的影响与大脑皮质内NF-κB及Bcl-2和Bax表达的关系,从而探讨姜黄素治疗AD的可能机制。方法将90只大鼠随机分为6组,AD模型组、AD模型+姜黄素低剂量组、AD模型+姜黄素中剂量组、AD模型+姜黄素高剂量组、假手术组和正常对照组,每组各15只。各组大鼠均通过Morris水迷宫观察其学习记忆能力的改变;采用免疫组织化学方法结合图像分析观察各组大鼠大脑皮质的NF-κB免疫反应性细胞的表达变化,采用Western blot方法检测各组大鼠大脑皮质Bcl-2和Bax蛋白的表达。结果姜黄素可有效改善AD大鼠的学习记忆能力,并呈剂效关系,大剂量的效果更好。姜黄素可以缩短AD模型大鼠水迷宫测试的潜伏期(P<0.05),姜黄素低、中、高剂量治疗组大鼠寻找目标象限所需时间缩短;免疫组织化学结果显示:模型组NF-κB蛋白表达较对照组降低(P<0.01);姜黄素各剂量组NF-κB蛋白表达较模型组增高(P<0.05),且姜黄素高剂量组高于姜黄素低剂量组(P<0.05)。Western blot结果显示:Bcl-2蛋白与NF-κB在各组大鼠大脑皮质中的表达趋于一致;模型组Bcl-2蛋白表达与正常对照组比较差异有统计学意义(P<0.01);姜黄素各剂量[30、60、100 mg/(kg·d)]组Bcl-2蛋白表达较模型组分别增加14.56%、22.12%和32.87%(P<0.05)。AD模型组大鼠大脑皮质Bax蛋白表达与正常对照组比较差异有统计学意义(P<0.01);姜黄素不同剂量[30、60、100 mg/(kg·d)]组Bax蛋白表达与AD模型比较,分别减少26.37%、37.56%和47.32%(P<0.05)。结论姜黄素可效改善AD大鼠的学习记忆能力,且随着剂量的增加治疗效果改善更加明显;姜黄素促进Bcl-2的上调及Bax的减少可能是姜黄素改善AD大鼠学习记忆能力的机制之一;姜黄素可通过激活大脑皮质NF-κB途径调控凋亡调节基因的表达而发挥对AD的治疗作用。
Objective To observe the amelioration and mechanism of curcumin on the learning and memory ability of AD rats,in order to understand the impact of AD rats learning and memory abilities and brain cortex NF-κB,Bax and Bcl-2 expression and the relationship between so as to explore the possible mechanism of curcumin to treat AD. Methods 90 SD rats were divided randomly into the control group,imitated operating group,AD model group,AD model plus curcumin low level group,AD model plus curcumin low middle group,AD model plus curcumin high level group, each group of 15 rats.Groups of rats were observed by Morris water maze changes in its learning and memory ability. The immunohistochemical method and combining with image were Used to analysis to observe each rat cerebral cortex of the NF-KB changes the expression of cell immune response,the Western blot method was used to detect the Bcl-2 each rat brain cortex and the expression of Bax protein.Results Curcumin had ability of therapy on AD,curcumin could ameliorate the learning and memory ability of AD rats,and showed dose dependence.Curcumin could shorten the incu- bation period of experimental rats testing in water maze.Immunohistochemical results showed：the expression of NF-κB was degraded in the cortex of AD model rats compare with the control group （P〈O.O1）.Curcumin could raise the expression of NF-κB in the cortex of AD model rats （P〈0.05）,and AD model plus curcumin high group was higher than low level group （P〈0.05）.The Bcl-2 protein and the NF-κB in each group to have consistent expression in cortex of rats,the Bcl-2 protein in the model group expression differences compared with normal control group was statistically significant （P〈0.01）.Curcumin each dose 30,60,100 mg/（kg-d） group the Bcl-2 protein expression increased by 14.56%,22.12% and 32.87% respectively than model group （P〈0.05）.Bax protein expression in the rat brain cortex AD model group compared with normal control group,the difference was statistically significant （P〈O.01）.Curcumin each dose 30,60,100 mg/（kg ·d） group Bax protein expression and AD model was reduced by 26.37%,37.56% and 47.32% respectively （P〈0.05）. Conclusion Curcumin has the therapeutic action to AD,and improve the learning and memory a- bility of AD rats.The therapeutic action ameliorated of curcumin to Alzheimer disease are related with decreased the expression of Bax and increased expression of Bcl-2.Curcumin has therapeutical effect on AD through regulating the exnression of NF-KB and anontosis related zenes.
出处
《中国当代医药》
2014年第12期4-7,11,共5页
China Modern Medicine
基金
包头医学院第四附属医院自研项目(2013-02)
