益智健腦顆粒對(duì)AD模型大鼠海馬區(qū)Nrf2和8-iso-PG F2α表達(dá)的影響
本文選題:益智健腦顆粒 + 阿爾茨海默病; 參考:《中南大學(xué)》2012年碩士論文
【摘要】:目的: 研究補(bǔ)腎活血復(fù)方益智健腦顆粒對(duì)阿爾茨海默病(Alzheimer's disease, AD)模型大鼠學(xué)習(xí)記憶能力以及對(duì)核因子NF-E2相關(guān)因子(nuclear factor-erythroid2-related factor2, Nrf2)和8-異構(gòu)前列腺素F2a (8-iso-prostaglandin F2a,8-iso-PG F2a)表達(dá)的影響,從而探討中藥益智健腦顆粒防治阿爾茨海默病的部分作用機(jī)理。方法: 將40只雄性SD大鼠隨機(jī)分為4組,分別為正常組(n=10)、假手術(shù)組(n=10)、模型組(n=10)、補(bǔ)腎活血組(n=10)。模型組和補(bǔ)腎活血組大鼠采用D-半乳糖腹腔注射復(fù)合雙側(cè)海馬CA1區(qū)注射p淀粉樣蛋白25-35(Aβ25-35)造模,假手術(shù)組雙側(cè)海馬CA1區(qū)注射等體積的雙蒸水,正常組不作任何處理。造模后行Morris水迷宮試驗(yàn)(Morris water maze test, MWM)觀察造模是否成功。造模成功后補(bǔ)腎活血組予補(bǔ)腎活血復(fù)方益智健腦顆粒濃縮液灌胃治療8周,余3組大鼠均灌胃等體積雙蒸水對(duì)照,治療后再次進(jìn)行Morris水迷宮試驗(yàn),觀察各組大鼠學(xué)習(xí)記憶能力的改變,最后斷頭處死大鼠取雙側(cè)海馬組織,分別采用RT-PCR和ELISA檢測(cè)海馬組織中Nrf2和8-iso-PG F2α的表達(dá)水平。 結(jié)果: 1.行為學(xué)檢測(cè)結(jié)果:Morris水迷宮實(shí)驗(yàn)中,模型組、補(bǔ)腎活血組大鼠逃避潛伏期較正常組大鼠逃避潛伏期時(shí)間明顯延長(zhǎng)(P0.05),停留在原平臺(tái)象限的時(shí)間和穿越原平臺(tái)次數(shù)較正常組大鼠明顯減少(P0.05),而經(jīng)過(guò)中藥干預(yù)后的補(bǔ)腎活血組與模型組相比,能夠明顯縮短大鼠的逃避潛伏期(P0.05),增加其停留在原平臺(tái)象限的時(shí)間和穿越原平臺(tái)次數(shù)(P0.05),這說(shuō)明補(bǔ)腎活血方能有效的改善AD模型大鼠的學(xué)習(xí)、記憶能力。 2.RT-PCR結(jié)果:模型組與正常組相比較,模型組Nrf2表達(dá)明顯降低(P0.05),而假手術(shù)組則無(wú)統(tǒng)計(jì)學(xué)意義(P0.05);補(bǔ)腎活血組與模型組相比較,補(bǔ)腎活血組Nrf2表達(dá)明顯增多(P0.05)。 3.ELISA結(jié)果:模型組與正常組相比較,模型組中8-iso-PG F2α表達(dá)明顯增多,而假手術(shù)組則無(wú)統(tǒng)計(jì)學(xué)意義(P0.05);補(bǔ)腎活血組與模型組相比較,補(bǔ)腎活血組8-iso-PG F2α表達(dá)下降。 結(jié)論: 1.D-半乳糖腹腔注射復(fù)合雙側(cè)海馬注射β淀粉樣蛋白25-35(Aβ25-35)造?沙晒χ苽淅硐氲腁D模型。 2.補(bǔ)腎活血復(fù)方益智健腦顆?擅黠@改善AD模型大鼠的學(xué)習(xí)記憶能力。 3.益智健腦顆?梢陨险{(diào)Nrf2的表達(dá)以及降低8-iso-PG F2α的表達(dá),減輕機(jī)體氧化應(yīng)激作用,實(shí)現(xiàn)其對(duì)AD的治療。 4.AD模型大鼠腦內(nèi)Nrf2及8-iso-PG F2α表達(dá)變化,可能為AD發(fā)病的部分機(jī)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 偽 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 偽 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 偽 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 偽, alleviate the oxidative stress and realize the treatment of AD. The changes of Nrf2 and 8-iso-PG F2 偽 expression in the brain of 4.AD model rats may be part of the pathogenesis of AD.
【學(xué)位授予單位】:中南大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2012
【分類號(hào)】:R285.5;R749.1
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