發(fā)布時間：2018-09-14 17:36

【摘要】：目的：探討GABAA受體反向激動劑L-655,708對丙泊酚麻醉大鼠認知功能的影響。 方法：2月齡雄性Wistar大鼠30只,體重180～220g,采用隨機數(shù)字表法,將其隨機分為6組(n=5)：生理鹽水組(C組)、L-655,708+生理鹽水組(LC組)、丙泊酚麻醉1h組(P1組)、L-655,708+丙泊酚麻醉1h組(LP1)、丙泊酚麻醉24h組(P24組)和L-655,708+丙泊酚麻醉24h組(LP24)。于用藥前及用藥后1h、24h用Morris水迷宮測試大鼠認知功能,隨后處死大鼠,取腦組織,分別采用HE染色和尼氏體染色觀察海馬區(qū)神經(jīng)細胞及尼氏體形態(tài)學變化、免疫組織化學法和免疫蛋白印跡法(Western blot)測定海馬區(qū)磷酸化Tau蛋白(Tau-pSer356)及總Tau蛋白(Tau-5)的表達水平。 結(jié)果：①與C組比較,P1組、P24組潛伏期延長,目標象限滯留時間縮短,海馬區(qū)Tau-pSer356表達上調(diào)(P0.05)；與P1組比較,LP1組、P24組潛伏期縮短,目標象限滯留時間延長,海馬區(qū)Tau-pSer356表達下調(diào)(P0.05)；與P24組比較,LP24組潛伏期縮短,目標象限滯留時間延長,海馬區(qū)Tau-pSer356表達下調(diào)(P0.05)；各組間平臺區(qū)域進入次數(shù)及Tau-5表達水平差異無統(tǒng)計學意義。②C組與LC組海馬區(qū)神經(jīng)細胞形態(tài)結(jié)構(gòu)完整,尼氏體深染并廣泛分布于胞漿和樹突；其余四組神經(jīng)細胞出現(xiàn)核固縮、核碎裂及核溶解,尼氏體淡染；然而P1組與LP1組、P24組與LP24組神經(jīng)細胞及尼氏體形態(tài)有無明顯差異仍有待進一步研究。 結(jié)論：L-655,708可下調(diào)丙泊酚麻醉大鼠海馬磷酸化Tau蛋白(Tau-pSer356)的表達,減輕大鼠認知功能損害,而對總Tau蛋白(Tau-5)的表達水平影響不大；丙泊酚麻醉后大鼠出現(xiàn)的認知功能障礙可能與海馬區(qū)Tau-pSer356的高表達、神經(jīng)細胞及尼氏體損傷有關(guān)。
[Abstract]:Objective: To investigate the effect of GABAA receptor Reverse agonist L-655708 on cognitive function in anesthetized rats induced by propofol.
METHODS: Thirty two-month-old male Wistar rats weighing 180-220 g were randomly divided into 6 groups (n=5): saline group (group C), L-655,708 + saline group (group LC), propofol anesthesia group 1 h (group P1), L-655,708 + propofol anesthesia group 1 h (group LP1), propofol anesthesia group 24 h (group P24) and L-655,708 + propofol anesthesia group 24 h (group LP24 h). Morris water maze was used to test the cognitive function of rats before and 1 hour and 24 hours after administration. Then the rats were sacrificed. The brain tissues were taken out to observe the morphological changes of neurons and Nissl bodies in the hippocampus by HE staining and Nissl staining respectively. The phosphorylated Tau protein (Tau-pS) in the hippocampus was determined by immunohistochemistry and Western blot. Er356) and the expression level of total Tau protein (Tau-5).
Results: Compared with group C, the latency of group P1 and P24 was prolonged, the target quadrant retention time was shortened, and the expression of Tau-pSer356 in hippocampus was up-regulated (P 0.05); Compared with group P1, the latency of group LP1 and P24 was shortened, the target quadrant retention time was prolonged, and the expression of Tau-pSer356 in hippocampus was down-regulated (P 0.05). The expression of Tau-pSer356 in hippocampus was down-regulated with prolonged retention time (P 0.05). There was no significant difference in the number of plateau entrance and the expression of Tau-5 between groups. However, whether there are significant differences in the morphology of nerve cells and Nissl bodies between P1 group and LP1 group, P24 group and LP24 group remains to be further studied.
CONCLUSION: L-655,708 can down-regulate the expression of phosphorylated Tau protein (Tau-pSer356) in the hippocampus of propofol anesthetized rats, alleviate the cognitive impairment of rats, but have little effect on the expression of total Tau protein (Tau-5); the cognitive impairment after propofol anesthesia may be related to the high expression of Tau-pSer356 in the hippocampus, neurons and Nissl bodies. Injury related.
【學位授予單位】：蘭州大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R614

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