益智健脑颗粒对AD模型大鼠海马区Nrf2和8-iso-PG F2α表达的影响

发布时间：2018-05-09 16:43

本文选题：益智健脑颗粒 + 阿尔茨海默病　；参考：《中南大学》2012年硕士论文

【摘要】：目的：研究补肾活血复方益智健脑颗粒对阿尔茨海默病(Alzheimer's disease, AD)模型大鼠学习记忆能力以及对核因子NF-E2相关因子(nuclear factor-erythroid2-related factor2, Nrf2)和8-异构前列腺素F2a (8-iso-prostaglandin F2a,8-iso-PG F2a)表达的影响,从而探讨中药益智健脑颗粒防治阿尔茨海默病的部分作用机理。方法：将40只雄性SD大鼠随机分为4组,分别为正常组(n=10)、假手术组(n=10)、模型组(n=10)、补肾活血组(n=10)。模型组和补肾活血组大鼠采用D-半乳糖腹腔注射复合双侧海马CA1区注射p淀粉样蛋白25-35(Aβ25-35)造模,假手术组双侧海马CA1区注射等体积的双蒸水,正常组不作任何处理。造模后行Morris水迷宫试验(Morris water maze test, MWM)观察造模是否成功。造模成功后补肾活血组予补肾活血复方益智健脑颗粒浓缩液灌胃治疗8周,余3组大鼠均灌胃等体积双蒸水对照,治疗后再次进行Morris水迷宫试验,观察各组大鼠学习记忆能力的改变,最后断头处死大鼠取双侧海马组织,分别采用RT-PCR和ELISA检测海马组织中Nrf2和8-iso-PG F2α的表达水平。结果： 1.行为学检测结果：Morris水迷宫实验中,模型组、补肾活血组大鼠逃避潜伏期较正常组大鼠逃避潜伏期时间明显延长(P0.05),停留在原平台象限的时间和穿越原平台次数较正常组大鼠明显减少(P0.05),而经过中药干预后的补肾活血组与模型组相比,能够明显缩短大鼠的逃避潜伏期(P0.05),增加其停留在原平台象限的时间和穿越原平台次数(P0.05),这说明补肾活血方能有效的改善AD模型大鼠的学习、记忆能力。 2.RT-PCR结果：模型组与正常组相比较,模型组Nrf2表达明显降低(P0.05),而假手术组则无统计学意义(P0.05)；补肾活血组与模型组相比较,补肾活血组Nrf2表达明显增多(P0.05)。 3.ELISA结果：模型组与正常组相比较,模型组中8-iso-PG F2α表达明显增多,而假手术组则无统计学意义(P0.05)；补肾活血组与模型组相比较,补肾活血组8-iso-PG F2α表达下降。结论： 1.D-半乳糖腹腔注射复合双侧海马注射β淀粉样蛋白25-35(Aβ25-35)造模可成功制备理想的AD模型。 2.补肾活血复方益智健脑颗粒可明显改善AD模型大鼠的学习记忆能力。 3.益智健脑颗粒可以上调Nrf2的表达以及降低8-iso-PG F2α的表达,减轻机体氧化应激作用,实现其对AD的治疗。 4.AD模型大鼠脑内Nrf2及8-iso-PG F2α表达变化,可能为AD发病的部分机制。
[Abstract]:Objective: To study the effects of Bushen Huoxue Yizhi Jiannao granule (YZJN) on learning and memory ability and the expression of nuclear factor NF-E2 related factors nuclear factor-erythroid2-related factor2 (Nrf2) and 8-iso-prostaglandin F2a8-iso-PG F2a in Alzheimer's disease rats. The mechanism of Yizhi Jiannao granule in preventing and treating Alzheimer's disease was discussed. Methods: Forty male SD rats were randomly divided into 4 groups: normal group (n = 10), sham operation group (n = 10), model group (n = 10), and tonifying kidney and activating blood group (n = 10). Model group and Bushen Huoxue group were treated by intraperitoneal injection of D-galactose and injection of amyloid 25-35A 尾 25-35 into bilateral hippocampal CA1 area. The rats in sham-operated group were injected with double-distilled water of the same volume in the CA1 area of hippocampus, but no treatment was given in the normal group. After modeling, Morris water maze test and Morris water maze test (MWM) were performed to observe whether the model was successful or not. After the successful establishment of the model, the Bushen Huoxue group was treated with Bushen Huoxue compound Yizhijiannao granule concentrated liquid for 8 weeks, and the remaining 3 groups were treated with the same volume double-steamed water as the control group. After the treatment, the Morris water maze test was performed again. The changes of learning and memory ability were observed in each group. Finally, the bilateral hippocampal tissues were killed and the expressions of Nrf2 and 8-iso-PG F2 伪 in hippocampus were detected by RT-PCR and ELISA, respectively. Results: 1. Behavioral test results: in the water maze experiment, the model group, The escape latency of Bushen Huoxue group was significantly longer than that of the normal group, and the time of staying in the original platform quadrant and the times of crossing the original platform decreased significantly than that of the normal group. Compared with model group, kidney activating blood group, It can obviously shorten the escape latency of rats, increase the time of staying in the original platform quadrant and the times of crossing the original platform, which indicates that Bushen Huoxue prescription can effectively improve the learning and memory ability of AD model rats. 2.RT-PCR results: compared with the normal group, the expression of Nrf2 in the model group was significantly lower than that in the control group, but in the sham operation group, there was no significant difference between the model group and the model group. Compared with the model group, the expression of Nrf2 in the model group was significantly higher than that in the model group. 3.ELISA results: compared with the normal group, the expression of 8-iso-PG F2 伪 in the model group was significantly increased, while that in the sham operation group was not significant (P 0.05), and the expression of 8-iso-PG F2 伪 in the model group was lower than that in the model group. Conclusion: 1. The ideal AD model was successfully established by intraperitoneal injection of D-galactose and bilateral hippocampal injection of 尾 -amyloid protein 25-35A 尾 25-35. 2. Bushen Huoxue compound Yizhi Jiannao granule can obviously improve the learning and memory ability of AD model rats. 3. Yizhijiannao granule can up-regulate the expression of Nrf2 and decrease the expression of 8-iso-PG F2 伪, alleviate the oxidative stress and realize the treatment of AD. The changes of Nrf2 and 8-iso-PG F2 伪 expression in the brain of 4.AD model rats may be part of the pathogenesis of AD.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R285.5;R749.1

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