發(fā)布時間：2018-01-17 17:03

  本文關鍵詞：補腎醒腦法對2型糖尿病認知功能障礙小鼠性激素信號通路相關激素水平、海馬Erα和ErβmRNA的影響研究　出處：《成都中醫(yī)藥大學》2016年博士論文　論文類型：學位論文

  更多相關文章： 2型糖尿病 認知功能障礙 補腎醒腦法 性激素 Erα和Erβ mRNA

【摘要】：本論文分為2型糖尿病(Type 2 Diabetes Mellitus T2DM)認知功能障礙與性激素信號通路相關性的理論探討和科學研究兩部分。第一部分理論探討從祖國醫(yī)學的角度出發(fā),結(jié)合導師觀點和自身研究,對消渴呆病(糖尿病認知功能障礙)的定義、病因病機、辨證論治和現(xiàn)代醫(yī)學研究進行簡要闡述。第二部分科學研究目的：研究2型糖尿病小鼠性激素信號通路中下丘腦-垂體-性腺軸(Hypothalamic-pituitary-gonadal axis HPG)中相關激素水平、海馬中Er α和Er β mRNA水平的表達,進而明確補腎醒腦法改善2型糖尿病認知功能障礙小鼠的認知能力與其對性激素信號通路某些環(huán)節(jié)的調(diào)控的相關性。方法：健康清潔級雌性8周齡昆明小鼠,為正常對照組；健康SPF級(specific pathogen free無特定病原體級)雌性8周齡KKay小鼠為實驗組。KKay小鼠,經(jīng)去勢手術(shù)和糖尿病認知功能障礙成模檢測成功后隨機分為模型對照組、陽性對照組、中藥組和中藥去勢組(中藥去勢組先行去卵巢手術(shù))。陽性對照組予吡拉西坦；中藥組、中藥去勢組予醒腦益智合劑；KKay小鼠糖尿病造模成功后均予羅格列酮常規(guī)控制血糖。給藥周期共計8周。在糖尿病成模后和給藥結(jié)束后分別各進行一次Morris水迷宮實驗。第二次水迷宮實驗結(jié)束后,及時于冰上進行實驗動物解剖及樣本制備。酶聯(lián)免疫分析法(Enzyme linked immunosorbent assay ELISA)檢測各組小鼠相關性激素水平；實時熒光定量聚合酶鏈式反應(Quantitative Real-time Polymerase Chain Reaction QRT-PCR)測定海馬中雌激素受體1 (Estrogen receptor Er a)和雌激素受體2 (Estrogen receptor Er β)mRNA的表達。結(jié)果：(1)第一次水迷宮實驗結(jié)果中正常對照組和各組糖尿病小鼠平臺潛伏期比較,各組均明顯偏高(P0.05),可見T2DM小鼠認知能力顯著低于正常小鼠。去卵巢后小鼠和其他各組小鼠比較P0.05,說明去勢后急速衰老的T2DM小鼠認知能力顯著低于正常小鼠和壯年的T2DM小鼠。第二次水迷宮實驗結(jié)果中正常對照組和模型對照組、中藥去勢組的小鼠比較P0.05,說明這兩組的認知能力顯著低于正常對照組。給藥前后比較：中藥去勢組、陽性對照組和中藥組水迷宮成績第二次都明顯好于第一次(P0.05),即經(jīng)吡拉西坦治療后T2DM小鼠和醒腦益智合劑治療后的T2DM小鼠、去勢的T2DM小鼠認知能力均明顯提高。(2)在HPG軸性激素水平研究中發(fā)現(xiàn)：模型對照組E2、P水平顯著低于正常組(P0.05)。模型對照組、陽性對照組、中藥去勢組的LH、FSH、PRL水平顯著高于正常組(P0.05),說明T2DM KKay小鼠、陽性對照組和急速衰老T2DM KKay小鼠的LH、FSH、PRL出現(xiàn)紊亂。而T的變化不大,沒有明顯統(tǒng)計學差異。在經(jīng)過醒腦益智合劑治療后中藥組E2、P顯著高于模型對照組(P0.05)。中藥組和正常對照組,中藥去勢組與模型組E2、P、LH、FSH比較時P0.05,沒有明顯統(tǒng)計學差異,這說明使用醒腦益智合劑治療2型糖尿病認知功能障礙KKay小鼠和其急速衰老小鼠模型是有效的,能調(diào)節(jié)HPG軸性激素的紊亂,糾正E2、P的低水平,降低LH、FSH的過高水平。(3)在小鼠海馬Er α和Er β mRNA的表達研究中：T2DM KKay小鼠和去勢的T2DM KKay小鼠Er α和Er β mRNA表達顯著低于正常水平(P0.05)；模型對照組和中藥組比較P0.05,有明顯統(tǒng)計學差異,模型對照組和中藥去勢組比較P0.05,沒有明顯統(tǒng)計學差異,說明經(jīng)醒腦益智合劑治療T2DM KKay小鼠和去勢T2DMKKay小鼠Er α和Er β mRNA表達能有所提高。中藥治療后T2DM KKay小鼠的Er α和Er β mRNA表達顯著高于模型對照組；治療后去勢T2DM KKay小鼠Er α和Er βmRNA表達升高接近模型對照組。陽性對照組和中藥去勢組、模型對照組Er α mRNA表達比較P0.05,有明顯統(tǒng)計學差異,說明吡拉西坦對小鼠Er α mRNA表達有一定影響,使Er α mRNA表達在一定程度上升高。模型對照組和陽性對照組Er β mRNA比較P0.05,沒有明顯統(tǒng)計學差異,說明吡拉西坦對T2DM小鼠Er β mRNA表達影響不大。結(jié)論：在常規(guī)控制血糖的基礎上,醒腦益智合劑能有效提高T2DM認知功能障礙小鼠和去勢后急速衰老的T2DM認知功能障礙小鼠的學習、記憶能力,其可能的作用機制可能是通過調(diào)整HPG性激素的水平,升高E2、P,降低LH、FSH;增強大腦海馬Er α和Er β mRNA水平的表達而達到的。
[Abstract]:This paper is divided into type 2 diabetes (Type 2 Diabetes Mellitus T2DM) cognitive theory and scientific research related dysfunction and sexual hormone signaling pathways of two parts. Starting from the perspective of traditional Chinese medicine combined with the first part of the theory, research ideas and their mentor cancellation, stay thirsty disease (diabetic cognitive dysfunction) definition, etiology machine, TCM and modern medicine research were briefly described. The second part of the scientific research objective: To study the type 2 diabetic mice sex hormone signaling in the hypothalamic pituitary gonadal axis (Hypothalamic-pituitary-gonadal axis HPG) in hormone levels, expression of hippocampal Er alpha and Er beta mRNA level, then clearly improve Bushenxingnao method the cognitive ability of type 2 diabetic mice with cognitive impairment on sex hormone signaling pathway in some segments of the control. Methods: healthy female 8 week old Kunming mice as normal control group; SPF (specific pathogen free healthy specific pathogen free) female 8 week old KKay mice to.KKay mice in the experimental group, after castration and diabetic cognitive dysfunction model after successful detection were randomly divided into model group, positive control group, Chinese medicine group and traditional Chinese medicine the ovariectomized group (Chinese medicine group first castrated ovariectomy). Positive control group treated with piracetam; traditional Chinese medicine group, Chinese medicine group received castration xinnaoyizhi Decoction; KKay mice rats were treated with rosiglitazone. The conventional control of blood glucose administration period a total of 8 weeks. After diabetic model and after medication respectively. The first Morris water maze test. The end of the second after the water maze test, in experimental animal anatomy and sample preparation on ice. Enzyme linked immunosorbent assay (Enzyme linked immunosorbent assay ELISA) to detect the small Correlation between hormone levels in rats; real-time fluorescence quantitative polymerase chain reaction (Quantitative Real-time Polymerase Chain Reaction QRT-PCR) determination of estrogen receptor in hippocampus (Estrogen 1 receptor Er a) and estrogen receptor 2 (Estrogen receptor Er) on the expression of mRNA. Results: (1) the first water maze test results in the normal control group and diabetic group platform mice incubation period between groups were significantly higher (P0.05), the cognitive ability of visible T2DM mice was significantly lower than that of normal mice. The ovariectomized mice and the mice in other groups compared with P0.05, said T2DM cognitive ability rapid aging Ming after castration was significantly lower than that of normal mice and T2DM mice. In the second water maze experiment results in normal control group and model control group, Chinese medicine group were castrated P0.05, illustrate the cognitive ability of the two groups were significantly lower than the control group. Before administration After comparison: Chinese medicine castration group, positive control group and Chinese medicine group water maze test second times better than the first time (P0.05), by Laci Staw after the treatment of T2DM mice and xingnaoyizhi mixture in the treatment of T2DM after castration mice, T2DM mice cognitive ability were significantly improved. (2) found in the study of sex hormones the HPG axis: the model control group E2, the level of P was significantly lower than that of normal group (P0.05). The model control group, positive control group, Chinese medicine LH FSH, castration group, PRL level was significantly higher than that of normal group (P0.05), T2DM KKay mice, positive control group and the rapid aging T2DM mice with KKay LH FSH. PRL and T disorders. Little change, no significant statistical difference. After xingnaoyizhi mixture after treatment in Chinese medicine group E2, P were significantly higher than the model group (P0.05). The Chinese medicine group and normal control group, Chinese medicine group and the ovariectomized model group E2, P, LH, FSH is P0.05, there is no clear Significant statistical difference, which shows that the use of xingnaoyizhi mixture in the treatment of type 2 diabetic cognitive dysfunction in KKay mice and the rapid aging mice model is effective and can regulate the HPG axis hormone disorder, correct E2, lower level, P LH, the high level of FSH. (3) the expression of alpha and Er in hippocampus of mice Er beta mRNA: T2DM KKay T2DM KKay mice and ovariectomized mice Er alpha and Er beta mRNA expression was significantly lower than the normal level (P0.05); model group and Chinese medicine group P0.05, there was significant difference in model control group and Chinese medicine castration group P0.05, no statistically significant difference, which shows that the effect of Xingnao Yizhi mixture the treatment of T2DM KKay mice and ovariectomized T2DMKKay mice Er alpha and Er beta mRNA expression can be increased. The expression of T2DM in mice after treatment with Chinese medicine KKay Er alpha and Er beta mRNA was significantly higher than that in the model control group; after treatment of ovariectomized female T2DM KKay mice Expression of Er alpha and Er beta mRNA increased to the model group. The positive control group and Chinese medicine castration group, model control group, Er mRNA expression of P0.05, there was significant difference that piracetam has a certain effect on the mice Er alpha mRNA expression, the Er expression of mRNA alpha high rise in a certain extent. The model control group and the positive control group Er beta mRNA P0.05, no significant difference, indicating piracetam has little effect on the T2DM expression of mouse Er beta mRNA. Conclusion: Based on conventional glucose control, Xingnao Yizhi mixture can effectively improve the T2DM cognitive dysfunction in mice after castration and rapidly aging T2DM cognitive dysfunction in mice's learning and memory ability. And the possible mechanism may be HPG by adjusting the level of sex hormones, increased E2, P, lower LH, FSH; enhance the expression of hippocampal Er alpha and Er beta mRNA level and to achieve.

【學位授予單位】：成都中醫(yī)藥大學
【學位級別】：博士
【學位授予年份】：2016
【分類號】：R259;R277.7

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