本文選題：阿爾茨海默病 + 嗅覺障礙��； 參考：《湖北中醫(yī)藥大學(xué)》2017年碩士論文

【摘要】：目的:系統(tǒng)評(píng)價(jià)嗅覺障礙與阿爾茨海默病之間的關(guān)系。方法:檢索中國(guó)生物醫(yī)學(xué)文獻(xiàn)數(shù)據(jù)庫(kù)(Sino Med)、相關(guān)期刊論文(CNKI)、維普期刊數(shù)據(jù)庫(kù)(VIP)、萬(wàn)方數(shù)據(jù)庫(kù)和Pub Med收錄的有關(guān)嗅覺障礙與阿爾茨海默病關(guān)系的病例對(duì)照研究,檢索時(shí)間截止2017年1月。研究者嚴(yán)格按照納入標(biāo)準(zhǔn)和排除標(biāo)準(zhǔn)篩選文獻(xiàn),并進(jìn)行質(zhì)量評(píng)價(jià)。運(yùn)用Review Manager 5.3軟件進(jìn)行Meta分析。結(jié)果:總共納入8篇文獻(xiàn),包含研究對(duì)象680例,其中阿爾茨海默病患者376例,對(duì)照者304例。經(jīng)Meta分析結(jié)果顯示,阿爾茨海默病患者嗅覺功能水平低于對(duì)照組,SMD=-1.66(95%CI:-1.84~-1.48,P0.0001)。漏斗圖顯示無(wú)發(fā)表偏倚。結(jié)論:嗅覺障礙與阿爾茨海默病可能存在一定的關(guān)聯(lián)性。目的:通過觀察大鼠腦內(nèi)星形膠質(zhì)細(xì)胞的激活、血清和腦內(nèi)炎性因子的水平、相關(guān)蛋白的表達(dá)和酶的變化,來探討AC介導(dǎo)的炎性反應(yīng)在AD模型大鼠中的作用機(jī)制及針灸干預(yù)對(duì)Aβ生成的影響,從而為AD的針灸治療提供依據(jù)。方法:將60只健康雄性Wistar大鼠,隨機(jī)分成正常組、假手術(shù)組、模型組和治療組,15只/組。采用微量注射法向大鼠海馬內(nèi)注射Aβ1-42制備AD模型,假手術(shù)組采用生理鹽水來替代Aβ1-42。正常組、假手術(shù)組和模型組不施以任何治療;治療組先針刺(毫針長(zhǎng)25mm,直徑0.35mm)百會(huì)、腎俞,再用特制艾條(直徑約5mm)在距離腧穴2~3cm上方進(jìn)行溫和灸,持續(xù)15分鐘,1次/日,6天/療程,共2療程,療程間隔1日。治療結(jié)束后,各組選取10只進(jìn)行指標(biāo)檢測(cè),(1)運(yùn)用ELISA、Western-Blot和免疫組化法分別檢測(cè)各組大鼠血清和腦組織炎性因子TNF-α、IFN-γ和TGF-β的水平。(2)運(yùn)用ELISA與Western-Blot法分別檢測(cè)各組大鼠血清BACE1的濃度和大鼠海馬區(qū)BACE、APP的蛋白表達(dá)水平。(3)運(yùn)用Western-Blot法檢測(cè)各組大鼠海馬區(qū)GFAP的蛋白表達(dá)水平。結(jié)果:(1)由ELISA、Western-Blot和免疫組化法結(jié)果可見,與正常組比較,模型組大鼠血清和海馬區(qū)TNF-α、IFN-γ的表達(dá)升高(均P0.05),TGF-β1的表達(dá)下降(P0.01);與模型組比較,治療組TNF-α、IFN-γ的表達(dá)下降(均P0.05),TGF-β1的表達(dá)明顯升高(P0.01)。(2)由ELISA法結(jié)果可見,與正常組比較,模型組大鼠血清BACE1的濃度升高(P0.01);與模型組比較,治療組大鼠血清BACE1的濃度下降(P0.01)。由Western-Blot法結(jié)果可見,與正常組比較,模型組大鼠海馬區(qū)BACE、APP的蛋白表達(dá)水平升高(均P0.01);而治療組較模型組表達(dá)下降(均P0.01)。(3)由Western-Blot法結(jié)果可見,與正常組比較,模型組大鼠海馬區(qū)GFAP的蛋白表達(dá)水平升高(P0.05);與模型組比較,治療組大鼠海馬區(qū)GFAP的蛋白表達(dá)水平略有下降,但二者無(wú)統(tǒng)計(jì)學(xué)差異(P0.05)。結(jié)論:AD模型大鼠伴隨星形膠質(zhì)細(xì)胞的激活,出現(xiàn)促炎因子TNF-α、IFN-γ的表達(dá)上調(diào)和抗炎因子TGF-β1的表達(dá)下調(diào),存在抗炎和促炎因子表達(dá)失衡的現(xiàn)象;同時(shí)促炎因子刺激AC可上調(diào)BACE1、APP的表達(dá),加速APP分解為Aβ。針灸可激活星形膠質(zhì)細(xì)胞表達(dá)抗炎性因子TGF-β1,并減少促炎因子TNF-α、IFN-γ的表達(dá),并使中樞和外周(腦和血清)炎性因子表達(dá)趨勢(shì)一致;同時(shí)減少BACE、APP的表達(dá),對(duì)Aβ的生成起到了干預(yù)作用,從而有效抑制AD炎癥級(jí)聯(lián)反應(yīng),改善AD大鼠的學(xué)習(xí)記憶能力。
[Abstract]:Objective: to systematically evaluate the relationship between olfactory disorder and Alzheimer's disease. Methods: a case-control study on the relationship between olfactory disorder and Alzheimer's disease was studied by searching the Chinese biomedical literature database (Sino Med), Chinese journal full text database (CNKI), VP journal database (VIP), Wanfang database and Pub Med. By January 2017, the researchers screened the literature strictly according to the inclusion criteria and exclusion criteria and carried out the quality evaluation. The Review Manager 5.3 software was used for Meta analysis. Results: a total of 8 articles were included, including 680 subjects, of which 376 patients with Alzheimer's disease and 304 of the illuminator. The results of Meta analysis showed Alzheimer's disease. The olfactory function of the patients was lower than that of the control group, SMD=-1.66 (95%CI:-1.84~-1.48, P0.0001). The funnel plot showed no publication bias. Conclusion: the olfactory disorder and Alzheimer's disease may have a certain correlation. Objective: To observe the activation of astrocytes in the brain, the level of inflammatory factors in the serum and brain, and the expression of related proteins in the brain of the rats. And the change of enzyme, to explore the mechanism of AC mediated inflammatory reaction in AD model rats and the effect of acupuncture and moxibustion intervention on the formation of A beta, so as to provide the basis for the acupuncture and moxibustion treatment of AD. Methods: 60 healthy male Wistar rats were randomly divided into normal group, sham operation group, model group and treatment group, and 15 rats were injected into the rat sea by microinjection. The AD model was prepared by injection of A beta 1-42. The sham operation group adopted physiological saline instead of the normal A beta 1-42. group. The sham operation group and the model group were not treated with any treatment. The treatment group first acupuncture (the needle length 25mm, the diameter 0.35mm) Baihui, Shenshu and the special bar (diameter about 5mm) were used for mild moxibustion at the distance from the acupoint 2~3cm, lasting 15 minutes, 1 times / day, 6 days. For a total of 2 courses, the course interval was 1 days. After the treatment, 10 indexes were detected in each group. (1) the levels of serum and brain inflammatory factors TNF- a, IFN- gamma and TGF- beta were detected by ELISA, Western-Blot and immunohistochemistry. (2) ELISA and Western-Blot were used to detect the serum BACE1 concentration in each group and the Western-Blot method respectively. The protein expression level of BACE and APP in the hippocampus of rats. (3) the protein expression level of GFAP in hippocampus of each group was detected by Western-Blot. Results: (1) the results of ELISA, Western-Blot and immunohistochemistry showed that the expression of TNF- A and IFN- y in the serum and hippocampus of the model rats increased (P0.05), and the expression of TGF- beta 1 decreased (P). 0.01): compared with the model group, the expression of TNF- alpha and IFN- gamma in the treatment group decreased (P0.05), and the expression of TGF- beta 1 increased significantly (P0.01). (2) the concentration of serum BACE1 in the model group was higher (P0.01) than that in the normal group (P0.01). Compared with the model group, the concentration of BACE1 in the serum of the treatment group decreased (P0.01). The result of Western-Blot method was possible. See, compared with the normal group, the protein expression level of BACE and APP in the hippocampus of model rats increased (P0.01), while the expression in the treatment group was lower than that in the model group (all P0.01). (3) the results of Western-Blot method showed that the protein expression level of GFAP in the hippocampus of model rats increased (P0.05) compared with the normal group (P0.05), and compared with the model group, the hippocampus of the treatment group was in the hippocampus. The protein expression level of GFAP decreased slightly, but there was no statistical difference between the two (P0.05). Conclusion: the AD model rats were associated with the activation of astrocytes, the expression of proinflammatory factor TNF- a, the up regulation of IFN- gamma and the down regulation of the expression of anti-inflammatory factor TGF- beta 1, and the imbalance of anti-inflammatory and proinflammatory factors, and the stimulating factor stimulated AC to increase BAC. The expression of E1 and APP accelerated the decomposition of APP into A beta. Acupuncture can activate astrocytes to express the anti-inflammatory factor TGF- beta 1, and reduce the expression of proinflammatory factor TNF- alpha and IFN- gamma, and make the central and peripheral (brain and serum) inflammatory factors in the same trend, and reduce BACE, APP's appearance at the same time, and interfere with the formation of A beta, thus effectively inhibiting AD. Inflammatory cascade improves the learning and memory ability of AD rats.
【學(xué)位授予單位】：湖北中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R246.6

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