L-655，708对丙泊酚麻醉大鼠认知功能的影响

发布时间：2018-09-14 17:36

【摘要】：目的：探讨GABAA受体反向激动剂L-655,708对丙泊酚麻醉大鼠认知功能的影响。方法：2月龄雄性Wistar大鼠30只,体重180～220g,采用随机数字表法,将其随机分为6组(n=5)：生理盐水组(C组)、L-655,708+生理盐水组(LC组)、丙泊酚麻醉1h组(P1组)、L-655,708+丙泊酚麻醉1h组(LP1)、丙泊酚麻醉24h组(P24组)和L-655,708+丙泊酚麻醉24h组(LP24)。于用药前及用药后1h、24h用Morris水迷宫测试大鼠认知功能,随后处死大鼠,取脑组织,分别采用HE染色和尼氏体染色观察海马区神经细胞及尼氏体形态学变化、免疫组织化学法和免疫蛋白印迹法(Western blot)测定海马区磷酸化Tau蛋白(Tau-pSer356)及总Tau蛋白(Tau-5)的表达水平。结果：①与C组比较,P1组、P24组潜伏期延长,目标象限滞留时间缩短,海马区Tau-pSer356表达上调(P0.05)；与P1组比较,LP1组、P24组潜伏期缩短,目标象限滞留时间延长,海马区Tau-pSer356表达下调(P0.05)；与P24组比较,LP24组潜伏期缩短,目标象限滞留时间延长,海马区Tau-pSer356表达下调(P0.05)；各组间平台区域进入次数及Tau-5表达水平差异无统计学意义。②C组与LC组海马区神经细胞形态结构完整,尼氏体深染并广泛分布于胞浆和树突；其余四组神经细胞出现核固缩、核碎裂及核溶解,尼氏体淡染；然而P1组与LP1组、P24组与LP24组神经细胞及尼氏体形态有无明显差异仍有待进一步研究。结论：L-655,708可下调丙泊酚麻醉大鼠海马磷酸化Tau蛋白(Tau-pSer356)的表达,减轻大鼠认知功能损害,而对总Tau蛋白(Tau-5)的表达水平影响不大；丙泊酚麻醉后大鼠出现的认知功能障碍可能与海马区Tau-pSer356的高表达、神经细胞及尼氏体损伤有关。
[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.
【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R614

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