尿石素A对小鼠异氟醚麻醉所致术后认知功能障碍的改善作用及其机制

Effect of urolithin A on postoperative cognitive dysfunction induced by isoflurane anesthesia in mice and its mechanism

摘要

目的 探讨尿石素A（UA）对长时程异氟醚麻醉所致小鼠术后认知功能障碍（POCD）的改善作用，并阐明其可能的作用机制。 方法 24只健康雄性C57BL/6小鼠随机分为空白对照组、麻醉组和UA组，每组8只。UA组小鼠于麻醉前2 d每天腹腔注射200 μL UA溶液，空白对照组和麻醉组小鼠给予等体积生理盐水，麻醉组和UA组小鼠制备长时程异氟醚麻醉模型，空白对照组小鼠不作处理。采用Y迷宫实验检测各组小鼠轮替正确率、移动距离和移动速度，条件恐惧实验检测各组小鼠僵直时间百分率，Western blotting法检测各组小鼠海马组织中白细胞介素（IL）-1β、IL-10和成熟脑源性神经营养因子（mBDNF）蛋白表达水平。 结果 Y迷宫实验，与空白对照组比较，麻醉组小鼠轮替正确率明显降低（P<0.01）；与麻醉组比较，UA组小鼠轮替正确率明显升高（P<0.01）。条件恐惧实验中情境记忆测试，与空白对照组比较，麻醉组小鼠僵直时间百分率明显降低（P<0.01）；与麻醉组比较，UA组小鼠僵直时间百分率明显升高（P<0.05）；线索记忆测试，各组小鼠僵直时间百分率比较差异无统计学意义（P>0.05）。Western blotting法，与空白对照组比较，麻醉组小鼠海马组织中IL-1β蛋白表达水平明显升高（P<0.01），IL-10和mBDNF蛋白表达水平明显降低（P<0.01）；与麻醉组比较，UA组小鼠海马组织中IL-1β蛋白表达水平明显降低（P<0.05），IL-10和mBDNF蛋白表达水平明显升高（P<0.05或P<0.01）。 结论 UA可以改善小鼠的POCD，其作用机制可能与UA的抗炎活性可抑制POCD小鼠的中枢炎症且上调mBDNF蛋白表达有关。

Abstract

Objective To discuss the improvement effect of uric acid （UA） on the postoperative cognitive dysfunction （POCD） in the mice anesthetized with isoflurane for a long duration， and to clarify its possible mechanism. Methods Twenty-four healthy male C57BL/6 mice were randomly divided into blank control group，anesthesia group， and UA group, and there were eight mice in each group. The mice in UA group were injected intraperitoneally with 200 μL UA solution daily for 2 d before anesthesia. The mice in blank control group and anesthesia group were given the same volume of saline; the mice in anesthesia group and UA group were used to prepare the models of long-duration isoflurane anesthesia， while the mice in blank control group were untreated. Y-maze tests was used to detect the alternation success rate， movement distances， and movement speeds of the mice in various groups； situational fear experiment was used to detect the percentages of freezing time； Western blotting method was used to detect the expression levels of interleukin (IL)-1β， IL-10， and mature brain-derived neurotrophic factor (mBDNF) proteins in hippocampus tissue of the mice in various groups. Results The Y-maze test results showed that compared with blank control group， the alternation success rate of the mice in anesthesia group was significantly decreased (P<0.01)； compared with anesthesia group， the alternation success rate of the mice in UA group was significantly increased (P<0.01). The situational fear experiment results showed that compared with blank control group, the percentage of freezing time of the mice in anesthesia group was significantly decreased (P<0.01)； compared with anesthesia group， the percentage of freezing time of the mice in UA group was significantly increased (P<0.05). The cued memory experiment resutls showed that there were no significant differences of the percentage of freezing time of the mice between various groups (P>0.05). The Western blotting results showed that compared with blank control group， the expression level of IL-1β protein in hippocampus tissue of the mice in anesthesia group was increased (P<0.01)， while the expression levels of IL-10 and mBDNF proteins were decreased (P<0.01)； compared with anesthesia group, the expression level of IL-1β protein in hippocampus tissue of the mice in UA group was decreased (P<0.05), and the expression levels of IL-10 and mBDNF proteins were increased (P<0.05 or P<0.01). Conclusion UA can improve the POCD in the mice, and its mechnasim may be related with its anti-inflammatory activity inhibiting the central inflammation and upregulating the mBDNF protein expression.

关键词

尿石素A / 异氟醚 / 术后认知功能障碍 / 白细胞介素 / 脑源性神经营养因子

Key words

Urolithin A / Isoflurane / Postoperative cognitive dysfunction / Interleukin / Brain-derived neurotrophic factor

Author summay

许敏慧（1998-），女，安徽省合肥市人，在读硕士研究生，主要从事术后认知功能障碍方面的研究。