异丙酚和七氟醚麻醉对老龄小鼠认知功能和海马β淀粉样蛋白沉积的影响

Effects of propofol and sevoflurane anesthesia on cognitive function and amyloid beta protein deposition in hippocampi of aged mice

目的：评价异丙酚和七氟醚麻醉对老龄小鼠认知功能和海马β淀粉样蛋白（Aβ）沉积的影响。方法 SAMP8小鼠36只，6月龄，体重29～32 g，采用随机数字表法，将其分为4组（ n＝9）：正常对照组（C组）、异丙酚麻醉组（P 组）、七氟醚麻醉组（S组）和异丙酚复合七氟醚麻醉组（PS组）。 P组腹腔注射异丙酚140 mg∕kg，首次出现翻正反射时追加异丙酚70 mg∕kg，再次出现时追加异丙酚40 mg∕kg；S组持续吸入2％七氟醚120 min；PS组腹腔注射异丙酚80 mg∕kg后持续吸入1％七氟醚120 min，出现翻正反射时追加异丙酚40 mg∕kg，3组均维持麻醉约120 min。分别于麻醉前及麻醉后7、14、28 d时进行Morris水迷宫实验，记录逃避潜伏期，然后取海马，采用免疫组化法检测Aβ表达。结果与C组比较，S组麻醉后7 d时逃避潜伏期延长，麻醉后7、14、28 d时海马Aβ表达上调（P＜0．05），P组和PS组上述指标差异无统计学意义（P＞0．05）；与麻醉后7 d时比较，S组麻醉后14、28 d时海马Aβ表达下调，C组、P组和PS组各时点海马Aβ表达差异无统计学意义（ P＞0．05）。结论七氟醚麻醉虽然可促进老龄小鼠海马Aβ沉积，但是仅导致短期认知功能障碍，而异丙酚及异丙酚复合七氟醚麻醉对其均无影响。

Objective To evaluate the effects of propofol and sevoflurane anesthesia on cognitive function and amyloid beta protein （ Aβ） deposition in hippocampi of aged mice. Methods Thirty-six SAMP8 mice, aged 6 months, weighing 29-32 g, were randomly assigned into 4 groups （ n=9 each） using a random number table： control group （ group C ） , propofol anesthesia group （ group P ） , sevoflurane anesthesia group （group S） and propofol plus sevoflurane anesthesia group （group PS）. In group P, propofol 140 mg∕kg was injected intraperitoneally, when righting reflex occurred, additional propofol 70 mg∕kg was given, and when it occurred again, additional propofol 40 mg∕kg was given. Group S continuously inhaled 1% sevoflurane for 120 min. Group PS continuously inhaled 2% sevoflurane for 120 min, and when righting reflex occurred, additional propofol 40 mg∕kg was given. Anesthesia was maintained for 120 min in P, S and PS groups. Before anesthesia and at 7, 14 and 28 days after anesthesia, Morris water maze test was performed, and the escape latency was recorded. Hippocampi were obtained to determine the expression of Aβ using immuno-histochemistry. Results Compared with group C, the escape latency was significantly prolonged at 7 days after anesthesia, and the expression of Aβwas up-regulated at 7, 14 and 28 days after anesthesia in group S, and no significant change was found in the parameters mentioned above in P and PS groups. Compared with the value at 7 days after anesthesia, the expression of Aβ was significantly down-regulated at 14 and 28 days after anesthesia in group S, and no significant change was found in the expression of Aβ at 14 and 28 days after anesthesia in C, P and PS groups. Conclusion Although sevoflurane anesthesia promotes Aβ deposition in hippocampi, it only causes short-term cognitive dysfunction, however, anesthesia with propofol or with propofol in combination with sevoflurane produces no influence in aged mice.