本文選題：阿爾茨海默病 + 自主跑輪運動�。� 參考：《山西醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:觀察自主跑輪運動對阿爾茨海默病(Alzheimer’s disease,AD)模型小鼠學(xué)習(xí)記憶能力和海馬內(nèi)炎性細(xì)胞因子表達(dá)的影響,探討自主跑輪運動改善AD學(xué)習(xí)記憶能力和神經(jīng)炎癥的機制,為神經(jīng)退行性疾病的防治提供新思路。方法:選取體重為30~35g的三月齡雄性昆明小鼠45只,由山西醫(yī)科大學(xué)實驗動物中心提供,隨機分成三組:(1)DMSO對照組;(2)AD安靜組;(3)AD運動組。每組15只。用3.5%水合氯醛腹腔注射麻醉小鼠,根據(jù)小鼠腦圖譜,采用腦立體定位儀,對DMSO對照組進(jìn)行側(cè)腦室注射DMSO,AD安靜組和AD運動組進(jìn)行側(cè)腦室注射Aβ1-42寡聚體。側(cè)腦室注射1周后,AD運動組小鼠進(jìn)行為期6周的自主跑輪運動,DMSO對照組和AD安靜組進(jìn)行正常飼養(yǎng),不運動。6周自主跑輪運動結(jié)束后,采用Morris水迷宮實驗,評估自主跑輪運動對AD模型小鼠學(xué)習(xí)記憶能力的影響。采用免疫熒光染色方法檢測小鼠海馬內(nèi)腫瘤壞死因子-α(Tumor necrosis factor-α,TNF-α)、白介素10(Interleukin 10,IL-10)、核轉(zhuǎn)錄因子κB(Nuclear factor Kappa B,NF-κB)的陽性表達(dá)率變化。采用蛋白印跡方法(Western blot)檢測小鼠海馬內(nèi)上述指標(biāo)的蛋白表達(dá)變化。結(jié)果:Morris水迷宮實驗結(jié)果顯示,6周自主跑輪運動結(jié)束后,AD運動組的逃避潛伏期(12.10±1.26)顯著低于AD安靜組(27.75±3.88)(P㩳0.01),提示6周的自主跑輪運動有效改善了AD模型小鼠的學(xué)習(xí)記憶能力。免疫熒光染色結(jié)果顯示,NF-κB、TNF-α和IL-10在DMSO對照組、AD安靜組和AD運動組海馬CA1區(qū)和CA3區(qū)均有表達(dá),且各自在兩區(qū)表達(dá)趨勢一致。在海馬CA1區(qū)和CA3區(qū),NF-κB和促炎細(xì)胞因子TNF-α在AD安靜組的陽性表達(dá)率均明顯高于其他兩組(P㩳0.05);而IL-10在AD安靜組的陽性表達(dá)率明顯低于AD運動組和DMSO對照組(P㩳0.05);而上述指標(biāo)在AD運動組和DMSO對照組的陽性表達(dá)率無明顯差異(P㧐0.05)。Western blot結(jié)果顯示,在小鼠海馬中,NF-κB和促炎細(xì)胞因子TNF-α在AD安靜組的蛋白表達(dá)量最高,與其余兩組均具有統(tǒng)計學(xué)差異(P㩳0.05);IL-10在AD安靜組的蛋白表達(dá)量最低,在AD運動組和DMSO對照組表達(dá)較高,且后兩者表達(dá)量較為接近,都與AD安靜組存在統(tǒng)計學(xué)差異(P㩳0.05)。結(jié)論:(1)自主跑輪運動有效改善了AD模型小鼠的學(xué)習(xí)記憶能力。(2)自主跑輪運動明顯下調(diào)了AD模型小鼠海馬內(nèi)促炎細(xì)胞因子TNF-α的釋放;上調(diào)了抗炎細(xì)胞因子IL-10的表達(dá)。(3)NF-κB通路的抑制在自主跑輪運動改善AD模型小鼠學(xué)習(xí)記憶能力方面起到關(guān)鍵作用。自主跑輪運動能夠顯著抑制過度活化的NF-κB、TNF-α級聯(lián)炎癥反應(yīng),并通過調(diào)控海馬內(nèi)炎癥反應(yīng)失衡狀態(tài),改善AD模型小鼠學(xué)習(xí)記憶能力。
[Abstract]:Objective: to observe the effects of self-running wheel exercise on learning and memory ability and the expression of inflammatory cytokines in hippocampus of Alzheimer's disease (AD) mice, and to explore the mechanism of self-running wheel exercise in improving AD learning and memory ability and neuroinflammation. To provide a new idea for the prevention and treatment of neurodegenerative diseases. Methods: a total of 45 male Kunming mice weighing 30 ~ 35g were randomly divided into three groups: the control group was divided into three groups. There were 15 rats in each group. Anesthetized mice were injected intraperitoneally with 3.5% chloral hydrate. According to the brain map of mice, A 尾 1-42 oligodeoxynucleotides were injected into the lateral ventricle of DMSO control group by intracerebroventricular injection of DMSO-AD quiescent group and AD exercise group by intracerebroventricular injection of A 尾 1-42 oligomer. One week after intracerebroventricular injection, the mice in AD exercise group were fed with DMSO control group and AD quiet group for 6 weeks, and the Morris water maze test was used after 6 weeks of exercise. To evaluate the effect of self-running wheel exercise on learning and memory ability of AD model mice. The positive expression of tumor necrosis factor- 偽 (Tumor necrosis factor- 偽), interleukin-10 (10(Interleukin 10) IL-10 and nuclear transcription factor 魏 B(Nuclear factor Kappa (NF- 魏 B) in the hippocampus of mice were detected by immunofluorescence staining. Western blot was used to detect the protein expression of the above indexes in the hippocampus of mice. Results the results of the water maze test showed that the escape latency of AD group was significantly lower than that of AD group (27.75 鹵3.88) after 6-week self-running. It suggested that 6-week self-running exercise could effectively improve the learning and memory ability of AD model mice. The results of immunofluorescence staining showed that TNF- 偽 and IL-10 were expressed in the CA1 and CA3 regions of hippocampus in AD quiet group and AD exercise group in DMSO control group, and the expression trend was the same in the two regions. The positive expression rates of NF- 魏 B and TNF- 偽 in hippocampal CA1 and CA3 regions were significantly higher in the quiet AD group than in the other two groups, while the positive expression rate of IL-10 in the AD quiet group was significantly lower than that in the AD exercise group and the DMSO control group. There was no significant difference in the positive expression rate between AD exercise group and DMSO control group. The results of Western blot showed that there was no significant difference between AD exercise group and DMSO control group. In the hippocampus of mice, the expression of NF- 魏 B and TNF- 偽 was the highest in the quiet group of AD, and there was a statistical difference between the two groups. The expression of IL-10 was the lowest in the quiet group of AD, and was higher in the exercise group and DMSO control group. The expression of the latter two groups was similar to that of the quiet group, and there was a statistical difference between the two groups. Conclusion: (1) the ability of learning and memory of AD model mice was improved effectively by self-running wheel exercise.) the release of pro-inflammatory cytokine TNF- 偽 in hippocampus of AD model mice was significantly down-regulated by autonomic wheel running. The inhibition of NF- 魏 B pathway up-regulated the expression of anti-inflammatory cytokine IL-10 played a key role in improving the learning and memory ability of AD model mice. The autonomic wheel running could significantly inhibit the over-activated inflammatory reaction of NF- 魏 B- TNF- 偽 cascade, and improve the learning and memory ability of AD model mice by regulating the imbalance of inflammatory response in hippocampus.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R749.16;R-332

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