嗅觉障碍与阿尔茨海默病关系的Meta分析及针灸抗炎作用对Aβ生成的影响研究

发布时间：2018-06-12 15:27

本文选题：阿尔茨海默病 + 嗅觉障碍　；参考：《湖北中医药大学》2017年硕士论文

【摘要】：目的:系统评价嗅觉障碍与阿尔茨海默病之间的关系。方法:检索中国生物医学文献数据库(Sino Med)、相关期刊论文(CNKI)、维普期刊数据库(VIP)、万方数据库和Pub Med收录的有关嗅觉障碍与阿尔茨海默病关系的病例对照研究,检索时间截止2017年1月。研究者严格按照纳入标准和排除标准筛选文献,并进行质量评价。运用Review Manager 5.3软件进行Meta分析。结果:总共纳入8篇文献,包含研究对象680例,其中阿尔茨海默病患者376例,对照者304例。经Meta分析结果显示,阿尔茨海默病患者嗅觉功能水平低于对照组,SMD=-1.66(95%CI:-1.84~-1.48,P0.0001)。漏斗图显示无发表偏倚。结论:嗅觉障碍与阿尔茨海默病可能存在一定的关联性。目的:通过观察大鼠脑内星形胶质细胞的激活、血清和脑内炎性因子的水平、相关蛋白的表达和酶的变化,来探讨AC介导的炎性反应在AD模型大鼠中的作用机制及针灸干预对Aβ生成的影响,从而为AD的针灸治疗提供依据。方法:将60只健康雄性Wistar大鼠,随机分成正常组、假手术组、模型组和治疗组,15只/组。采用微量注射法向大鼠海马内注射Aβ1-42制备AD模型,假手术组采用生理盐水来替代Aβ1-42。正常组、假手术组和模型组不施以任何治疗;治疗组先针刺(毫针长25mm,直径0.35mm)百会、肾俞,再用特制艾条(直径约5mm)在距离腧穴2~3cm上方进行温和灸,持续15分钟,1次/日,6天/疗程,共2疗程,疗程间隔1日。治疗结束后,各组选取10只进行指标检测,(1)运用ELISA、Western-Blot和免疫组化法分别检测各组大鼠血清和脑组织炎性因子TNF-α、IFN-γ和TGF-β的水平。(2)运用ELISA与Western-Blot法分别检测各组大鼠血清BACE1的浓度和大鼠海马区BACE、APP的蛋白表达水平。(3)运用Western-Blot法检测各组大鼠海马区GFAP的蛋白表达水平。结果:(1)由ELISA、Western-Blot和免疫组化法结果可见,与正常组比较,模型组大鼠血清和海马区TNF-α、IFN-γ的表达升高(均P0.05),TGF-β1的表达下降(P0.01);与模型组比较,治疗组TNF-α、IFN-γ的表达下降(均P0.05),TGF-β1的表达明显升高(P0.01)。(2)由ELISA法结果可见,与正常组比较,模型组大鼠血清BACE1的浓度升高(P0.01);与模型组比较,治疗组大鼠血清BACE1的浓度下降(P0.01)。由Western-Blot法结果可见,与正常组比较,模型组大鼠海马区BACE、APP的蛋白表达水平升高(均P0.01);而治疗组较模型组表达下降(均P0.01)。(3)由Western-Blot法结果可见,与正常组比较,模型组大鼠海马区GFAP的蛋白表达水平升高(P0.05);与模型组比较,治疗组大鼠海马区GFAP的蛋白表达水平略有下降,但二者无统计学差异(P0.05)。结论:AD模型大鼠伴随星形胶质细胞的激活,出现促炎因子TNF-α、IFN-γ的表达上调和抗炎因子TGF-β1的表达下调,存在抗炎和促炎因子表达失衡的现象;同时促炎因子刺激AC可上调BACE1、APP的表达,加速APP分解为Aβ。针灸可激活星形胶质细胞表达抗炎性因子TGF-β1,并减少促炎因子TNF-α、IFN-γ的表达,并使中枢和外周(脑和血清)炎性因子表达趋势一致;同时减少BACE、APP的表达,对Aβ的生成起到了干预作用,从而有效抑制AD炎症级联反应,改善AD大鼠的学习记忆能力。
[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.
【学位授予单位】：湖北中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R246.6

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