目的 探討丙泊酚麻醉對(duì)老年大鼠術(shù)后認(rèn)知功能的影響及自噬在其中的作用。方法 將老年大鼠72只，隨機(jī)分為4組：對(duì)照組、丙泊酚組、雷帕霉素組、丙泊酚+雷帕霉素組。雷帕霉素組及丙泊酚+雷帕霉素組于麻醉前5 d ip雷帕霉素10 mg/kg，每天1次，麻醉當(dāng)日為麻醉前1 h注射，共6 d。丙泊酚組及丙泊酚+雷帕霉素組以20 mg/kg丙泊酚誘導(dǎo)麻醉，并以54 mg/kg/h維持4 h。采用Morris水迷宮評(píng)測(cè)大鼠學(xué)習(xí)與記憶功能；Western Blotting技術(shù)及免疫熒光觀察麻醉后24 h、6 d海馬區(qū)自噬相關(guān)蛋白的表達(dá)。結(jié)果 與對(duì)照組比較，丙泊酚組第1~3天逃避潛伏期顯著延長(zhǎng)（P<0.05、0.01），目標(biāo)象限探索時(shí)間明顯縮短，穿平臺(tái)次數(shù)明顯減少（P<0.05）；麻醉后24 h、6 d海馬區(qū)自噬相關(guān)蛋白LC3B、Beclin-1蛋白表達(dá)明顯減少，p62蛋白表達(dá)明顯增多（P<0.05）。與丙泊酚組比較，丙泊酚+雷帕霉素組第1~3天逃避潛伏期縮短，目標(biāo)象限探索時(shí)間顯著延長(zhǎng)，穿平臺(tái)次數(shù)明顯增加（P<0.05）；麻醉后24 h、6 d海馬區(qū)自噬相關(guān)蛋白LC3B、Beclin-1表達(dá)明顯增多，p62表達(dá)明顯減少（P<0.05）。結(jié)論 丙泊酚連續(xù)麻醉4 h可導(dǎo)致老年大鼠空間學(xué)習(xí)記憶能力損傷，其機(jī)制可能與抑制海馬區(qū)自噬有關(guān)。

Objective To investigate the influence of propofol on learning and memory, and to identify the potential role of hippocampal autophagy in propofol-induced cognitive alterations in aged rats. Methods Tatolly 72 rats were randomly divided into four groups as follow:control group, propofol group (PRO), rapamycin group (RAP), and propofol + rapamycin group (PRO+RAP). Rats in RAP and PRO+RAP groups were ip injected with 10 mg/kg rapamycin beginning five days before propofol exposure. On the sixth day, rapamycin was administered 1 h before propofol anesthesia. Rats in both the PRO and PRO+RAP groups received 20 mg/kg propofol to induce anesthesia and then 54 mg/kg/h propofol to maintain anesthesia for 4 h. The test of learning and memory was performed by Morris water maze. Autophagy-related proteins in hippocampal region were determined by Western blotting and immunofluorescent staining at 24 h and 6 d after anesthesia. Results Compared with the CON group, the escape latency significantly prolonged from 1-3 day, the probe time was significantly decreased, and the time of staying at the original platform quadrant was significantly shorter (P<0.05 and 0.01) in the PRO group. Autophagy-related proteins LC3B and Beclin-1 expression were significantly decreased and p62 expression was significantly increased (P<0.05). Compared with the PRO group, the escape latency significantly shortened from 1-3 day, the probe time was significantly increased, and the time of staying at the original platform quadrant was significantly longer in the PRO+RAP group (P<0.05), and autophagy-related proteins LC3B and Beclin-1expression were significantly increased and p62 expression was significantly decreased (P<0.05) in the PRO+RAP group. Conclusions Our in vivo study indicates that 4 h propofol anesthesia could induce cognitive impairment in aged rats and this may be caused by the inhibitory effects of autophagy in the hippocampus.

國(guó)家自然科學(xué)基金資助項(xiàng)目（81571036）；國(guó)家自然科學(xué)基金青年基金資助項(xiàng)目（81600933）