本文選題：阿爾茨海默病　切入點(diǎn)：星形膠質(zhì)細(xì)胞　出處：《湖北中醫(yī)藥大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:老年斑是阿爾茨海默病特征性病理改變之一,β淀粉樣蛋白是老年斑的核心物質(zhì),因此減少Aβ的過量生成或加速其內(nèi)化,減少Aβ的聚集、沉降,是改善阿爾茨海默病病理進(jìn)程的重要途徑之一。根據(jù)目前已經(jīng)發(fā)表的研究文獻(xiàn),有關(guān)Aβ的生成途徑方面的研究已有了一定深度的探索,而有關(guān)Aβ內(nèi)化方面的研究還需要更進(jìn)一步的深入。本課題從Aβ降解的方面進(jìn)行研究,選取脂蛋白酯酶、抗凝乳蛋白酶α、載脂蛋白E作為研究指標(biāo),通過觀察針灸百會(huì)和腎俞穴對(duì)星形膠質(zhì)細(xì)胞的激活,及此三種蛋白酶與Aβ關(guān)系,探討“益腎調(diào)督”針灸法治療阿爾茨海默病的可能作用機(jī)制。方法:選用Wistar大鼠、SPF級(jí)、雄性、體重(360±20)g,造模前所有大鼠經(jīng)Morris水迷宮篩選,將符合條件的60只Wistar大鼠隨機(jī)分為正常組、假手術(shù)組、模型組、治療組。模型組用微量注射法向雙側(cè)海馬區(qū)各注射5μL寡聚態(tài)Aβ1-42;假手術(shù)組用同樣方法在雙側(cè)海馬區(qū)注射與Aβ1-42等量的生理鹽水;治療組在造模成功的基礎(chǔ)上選取百會(huì)穴和腎俞穴進(jìn)行常規(guī)針刺(針具規(guī)格:長(zhǎng)25mm直徑0.35mm毫針),選用細(xì)艾條(半徑約0.25mm)在大鼠腧穴上方2~3cm處進(jìn)行溫和灸,每穴15min;正常組不做任何處理,常規(guī)飼養(yǎng)。每日1次,6天為1個(gè)療程,共2個(gè)療程,療程間休息1日。針灸治療結(jié)束后,各組選取10只進(jìn)行指標(biāo)檢測(cè):(1)采用Morris水迷宮檢測(cè)大鼠的學(xué)習(xí)記憶能力;(2)采用ELISA法檢測(cè)血清中Aβ1-42的含量;(3)采用免疫組化法檢測(cè)大鼠海馬區(qū)GFAP蛋白的表達(dá)水平;(4)采用Western-Blot法檢測(cè)大鼠海馬區(qū)GFAP和Aβ內(nèi)化相關(guān)蛋白酶ACT、LPL、ApoE的表達(dá)。結(jié)果:兩個(gè)療程治療結(jié)束后,(1)行為學(xué)觀察:與模型組相比,治療組大鼠跨越平臺(tái)數(shù)增加(P0.01),而逃避潛伏期則縮短(P0.01)。(2)ELISA檢測(cè)結(jié)果:與正常組相比,模型組Aβ1-42明顯升高(P0.01),假手術(shù)組Aβ1-42未有明顯差異(P0.05);與模型組相比,治療組Aβ1-42明顯降低(P0.05)。(3)免疫組化結(jié)果:和正常組相比,模型組GFAP表達(dá)升高,具有統(tǒng)計(jì)學(xué)差異(P0.01);和模型組相比,治療組平均光密度值沒有顯著差異(P0.05);和正常組比較,治療組GFAP平均光密度值具有顯著差異(P0.05)。(4)Western-Blot檢測(cè)結(jié)果:與正常組相比,模型組GFAP蛋白表達(dá)顯著升高(P0.01),假手術(shù)組GFAP表達(dá)則未有明顯差異(P0.05);與模型組相比,治療組GFAP表達(dá)稍降低,無統(tǒng)計(jì)學(xué)差異(P0.05)。與正常組相比,模型組LPL、ApoE蛋白表達(dá)顯著降低(P0.01),ACT表達(dá)顯著升高(P0.01),假手術(shù)組LPL、ApoE、ACT表達(dá)則未有明顯差異(P0.05);與模型組比較,治療組LPL、ApoE表達(dá)顯著升高(P0.05),ACT表達(dá)顯著降低(P0.05)。結(jié)論:“益腎調(diào)督”針灸法可以通過上調(diào)大鼠海馬區(qū)LPL和ApoE的表達(dá),下調(diào)ACT的含量,促進(jìn)Aβ的內(nèi)化,減少β淀粉樣蛋白的沉積,從而延緩或改善阿爾茨海默病的病理進(jìn)程。
[Abstract]:Objective: senile plaque is one of the characteristic pathological changes of Alzheimer's disease, 尾 -amyloid protein is the core substance of senile plaque, so it reduces the excessive production of A 尾 or accelerates its internalization, reduces the aggregation and sedimentation of A 尾. It is one of the important ways to improve the pathological process of Alzheimer's disease. According to the published research literature, the research on the pathway of A 尾 production has been deeply explored. However, the study on A 尾 internalization needs further study. In this study, lipoprotein esterase, anticoagulase 偽 and apolipoprotein E were selected as the research indexes from the aspect of A 尾 degradation. By observing the activation of astrocytes at Baihui and Shenshu points of acupuncture and moxibustion, and the relationship between these three proteases and A 尾, the possible mechanism of acupuncture and moxibustion method of "tonifying kidney and regulating du" in treating Alzheimer's disease was discussed. All the rats were screened by Morris water maze before modeling. 60 Wistar rats were randomly divided into normal group, sham operation group and model group. In the model group, 5 渭 L oligomeric A 尾 1-42 was injected into the bilateral hippocampal area by microinjection, while in the sham operation group, the same amount of normal saline as A 尾 1-42 was injected in the bilateral hippocampal area. On the basis of successful modeling, the treatment group selected Baihui point and Shenshu point for routine acupuncture (needle size: 25mm in diameter: 0.35 mm in diameter), and selected fine moxa bar (radius about 0.25 mm) for mild moxibustion at 2cm above the acupoint of rats. Each acupoint 15 minutes; normal group do not do any treatment, routine feeding. Once a day for 6 days as a course of treatment, a total of 2 courses of treatment between the rest on 1st. After acupuncture treatment, 10 rats in each group were selected for index detection. (Morris water maze was used to detect the learning and memory ability of rats.) the content of A 尾 1-42 in serum was detected by ELISA method. The expression level of GFAP protein in hippocampal area of rats was detected by immunohistochemical method. Western-Blot method was used to detect the expression of GFAP and A 尾 -internalization-associated protease ACTLPLApoE in the hippocampus of rats. Results: after two courses of treatment, we observed the behavior: compared with the model group, In the treatment group, the number of cross platform increased, while the escape latency was shortened. The results of Elisa: compared with the normal group, A 尾 1-42 in the model group was significantly higher than that in the control group, and there was no significant difference in A 尾 1-42 between the sham operation group and the model group, while in the model group, there was no significant difference between the two groups, while in the model group, there was no significant difference between the two groups. Compared with the normal group, the expression of GFAP in the model group was significantly higher than that in the control group (P 0.01), and there was no significant difference in the mean optical density between the treatment group and the model group (P 0.05). The results of Western-Blot analysis showed that the expression of GFAP protein in the model group was significantly higher than that in the normal group, but there was no significant difference in the expression of GFAP in the sham operation group, and the expression of GFAP in the treatment group was slightly lower than that in the model group. Compared with the normal group, the expression of LPLApoE protein in the model group was significantly lower than that in the control group, and the expression of P0.01ACT in the model group was significantly higher than that in the sham operation group, but there was no significant difference in the expression of ACT between the model group and the model group, and there was no significant difference in the expression of ACT between the model group and the model group, and there was no significant difference in the expression of ACT between the model group and the model group. In the treatment group, the expression of LPLO ApoE increased significantly and the expression of P0.05ACT decreased significantly. Conclusion: the acupuncture and moxibustion method of "tonifying kidney and regulating du" can down-regulate the content of ACT, promote the internalization of A 尾 and reduce the deposition of 尾 -amyloid protein by up-regulating the expression of LPL and ApoE in hippocampus of rats. Thus delaying or improving the pathological process of Alzheimer's disease.
【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)】：R245;R-332

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