發(fā)布時間：2018-07-16 11:30

【摘要】：大腦海馬與認(rèn)知功能之間的關(guān)系一直都是研究熱點,但其對內(nèi)臟活動之間的影響知之甚少。臨床特征上,老年癡呆患者往往伴有代謝水平異常,具資料報道,有高達81%的散發(fā)性老年癡呆患者出現(xiàn)不同程度的代謝異常特征。3-輕基-3-甲基戊二酰輔酶A還原酶(3-hydroxy-3-methylglutaryl-Coenzyme Areductase,HMG-CR)是脂代謝的關(guān)鍵酶,本實驗通過SD大鼠構(gòu)建認(rèn)知障礙動物模型,探討海馬認(rèn)知障礙對血脂水平的影響及其與肝臟HMG-CR表達的關(guān)系,為脂代謝的深入研究提供實驗依據(jù)。為探討認(rèn)知障礙大鼠血脂水平,采用Aβ1-42大鼠海馬內(nèi)注射構(gòu)建認(rèn)知障礙動物模型,全自動生化分析儀檢測血脂水平。結(jié)果顯示,實驗組大鼠逃避潛伏期、跨越平臺的次數(shù)、在原平臺象限時間百分比分別為(75.19±2.24)s、(1.68±0.83)次、17.33%土4.75%與假手術(shù)組和對照組比較,均有顯著性差異(P0.05)。實驗組大鼠TG、TC、LDL分別為(2.30±0.08)mmol/L、(4.60±0.10)mmol/L、(2.41±0.06)mmol/L,與假手術(shù)組和對照組相比均顯著升高(P0.05)。為探討大鼠血脂水平變化是否與大鼠海馬神經(jīng)元凋亡有關(guān),采用TUNEL法檢測大鼠海馬神經(jīng)元凋亡,結(jié)果顯示,實驗組大鼠海馬神經(jīng)元凋亡指數(shù)為67.73土4.38%,假手術(shù)組和對照組分別為19.88±4.31%、16.45±5.50%,與實驗組比較,均有顯著性差異(P0.05)。為探討認(rèn)知障礙SD大鼠肝臟HMG-CR的表達情況,采用半定量反轉(zhuǎn)錄-聚合酶鏈反應(yīng)法(RT-PCR)檢測實驗大鼠肝臟HMG-CRmRNA的表達,蛋白印跡法(Westem Blot)檢測實驗大鼠肝臟HMG-CR的表達。實驗結(jié)果顯示,實驗組大鼠中肝臟HMG-CRmRNA的表達水平為0.49±0.03,明顯高于假手術(shù)組和對照組(P0.05);實驗組大鼠中肝臟HMG-CR的表達水平為0.50±0.02,顯著高于假手術(shù)組與對照組(P0.05)。綜上所述,Aβ1-42大鼠海馬內(nèi)注射可成功制備大鼠海馬認(rèn)知障礙模型,且海馬認(rèn)知障礙可引起實驗大鼠血脂水平升高,這一機制可能與認(rèn)知障礙實驗大鼠肝臟HMG-CR的表達水平升高有關(guān)。
[Abstract]:The relationship between hippocampus and cognitive function has been a hot topic, but its influence on visceral activity is poorly understood. Clinically, Alzheimer's patients are often accompanied by abnormal metabolic levels, which have been reported. Up to 81% of the sporadic dementia patients had different metabolic characteristics. 3-hydroxy-3-methylglutaryl-Coenzyme reductase-A reductase (HMG-CR) was a key enzyme in lipid metabolism. A cognitive impairment model was established in SD rats. To investigate the effect of hippocampal cognitive impairment on serum lipids and its relationship with HMG-CR expression in liver, and to provide experimental evidence for the further study of lipid metabolism. In order to investigate the level of blood lipid in cognitive impaired rats, a rat model of cognitive impairment was established by intrahippocampal injection of A 尾 1-42 rats, and blood lipids were measured by automatic biochemical analyzer. The results showed that the percentage of escape latency and the times of crossing the platform in the original platform quadrant were (75.19 鹵2.24) s, (1.68 鹵0.83) times (17.33% 鹵4.75%), which were significantly different from those in the sham operation group and the control group (P0.05). Compared with sham operation group and control group, the LDL levels of TGN TCU in experimental group were (2.30 鹵0.08) mmol / L, (4.60 鹵0.10) mmol / L and (2.41 鹵0.06) mmol / L, significantly higher than those in sham operation group and control group (P0.05). In order to investigate whether the changes of serum lipids were related to the apoptosis of rat hippocampal neurons, Tunel method was used to detect the apoptosis of rat hippocampal neurons. The apoptotic index of hippocampal neurons was 67.73 鹵4.38 in the experimental group, 19.88 鹵4.31 in the sham operation group and 16.45 鹵5.50 in the control group, respectively. There was significant difference between the experimental group and the experimental group (P0.05). In order to investigate the expression of HMG-CR in the liver of SD rats with cognitive impairment, the expression of HMG-CR mRNA was detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and the expression of HMG-CR was detected by Western blot. The results showed that the expression level of HMG-CR mRNA in liver of experimental group was 0.49 鹵0.03, which was significantly higher than that of sham operation group and control group (P0.05), and that of liver HMG-CR in experimental group was 0.50 鹵0.02, which was significantly higher than that in sham operation group and control group (P0.05). In conclusion, hippocampal cognitive impairment model of rats was successfully established by intrahippocampal injection of A 尾 1-42, and hippocampal cognitive impairment could induce the elevation of blood lipid level in experimental rats. This mechanism may be related to the increased expression of HMG-CR in the liver of experimental rats with cognitive impairment.
【學(xué)位授予單位】：廣西大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R-332;R749.16

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