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目的研究依托咪酯对大鼠空间学习记忆能力的影响。方法将30只雄性Wistar大鼠随机分为空白组、对照组、实验组,每组10只。空白组予以腹腔注射0.9%Na Cl 2 m L,对照组予以腹腔注射脂肪乳剂2 m L,实验组予以腹腔注射5mg·kg~(-1)依托咪酯(根据小鼠的体重约2 m L)。用Morris水迷宫行为学实验评价依托咪酯对大鼠空间学习记忆力的影响。用全细胞膜片钳技术观察依托咪酯(相当于5μmol·L~(-1))脂肪乳剂30 m L对大鼠海马CA1区神经元延长时程抑制(LTD)的影响。结果大鼠腹腔注射依托咪酯后逃避潜伏期延长,第3天的逃避潜伏期:空白组为(74±9)s,对照组为(62±10)s,实验组为(157±14)s,与空白组比较,对照组和实验组的差异有统计学意义(P<0.001)。大鼠寻找平台的路径所需的游泳路径延长,第3天的寻找平台的路径:空白组为(1262±413)cm,对照组为(1482±267)cm,实验组为(3859±802)cm,与空白组比较,对照组和实验组的差异有统计学意义(P<0.001)。给予低频刺激前,突触后兴奋性电流(EPSC)的基线值:对照组、实验组、空白组分别为(1.01±0.13),(0.99±0.07),(1.00±0.10)m V;给予低频刺激后持续40 min,这3组的EPSC值分别为(0.59±0.04),(0.44±0.05),(0.78±0.06)m V,分别为基线值的(54.7±4.0)%,(39.9±3.0)%,(78.3±5.0)%。与低频刺激前比较,对照组和实验组差异有统计学意义(P<0.05)。结论依托咪酯反复多次的使用可使大鼠的空间学习记忆能力受到影响,机制可能是使LTD增强。
Objective To study the effects of etomidate on spatial learning and memory in rats. Methods Thirty male Wistar rats were randomly divided into blank group, control group and experimental group, with 10 rats in each group. The blank group was intraperitoneally injected 0.9% Na Cl 2 m L, while the control group was injected intraperitoneally with 2 ml of fat emulsion. The experimental group was given intraperitoneal injection of 5 mg · kg -1 etomidate (according to the body weight of mice, about 2 m L ). Morris water maze behavioral test was used to evaluate the effect of etomidate on spatial learning and memory in rats. The effects of etomidate (equivalent to 5μmol·L -1) fat emulsion 30 m L on the prolonged time course inhibition (LTD) of hippocampal CA1 neurons were observed by whole cell patch clamp technique. Results The escape latency was prolonged after intraperitoneal injection of etomidate in rats. The escape latency on the third day was (74 ± 9) s in the blank group, (62 ± 10) s in the control group and (157 ± 14) s in the experimental group, Compared with the blank group, the difference between the control group and the experimental group was statistically significant (P <0.001). The path of swimming in rats looking for the path of the platform was prolonged. On the third day, the path of finding the platform was (1262 ± 413) cm in the blank group and (1482 ± 267) cm in the control group and 3859 ± 802 in the experimental group cm, compared with the blank group, the difference between the control group and the experimental group was statistically significant (P <0.001). Before the low-frequency stimulation, the baseline values of EPSC were (1.01 ± 0.13), (0.99 ± 0.07) and (1.00 ± 0.10) m V in the control group, experimental group and blank group respectively. The EPSC values of the three groups were (0.59 ± 0.04), (0.44 ± 0.05) and (0.78 ± 0.06) m V, respectively (54.7 ± 4.0% and 39.9 ± 3.0 )%, (78.3 ± 5.0)%. Compared with before low-frequency stimulation, the difference between the control group and the experimental group was statistically significant (P <0.05). Conclusion Repeated use of etomidate can affect the spatial learning and memory ability of rats, which may be due to the enhancement of LTD.