Li Wenyao, Chai Qing, Zhang Hongwei, Ma Jing, Xu Chengfen, Dong Jifu, Wei Xianghua, Wang Zhiyi, Zhang Kexian
Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
J Int Med Res. 2018 Apr;46(4):1404-1413. doi: 10.1177/0300060517754032. Epub 2018 Feb 19.
Objective Postoperative cognitive dysfunction (POCD) is common after surgery in elderly patients and is associated with high morbidity. The molecular mechanisms responsible for POCD are unknown. Minocycline, an inhibitor of microglial activation, may be useful in treating and preventing POCD. We explored whether minocycline can inhibit microglial activation and prevent POCD in aged rats as a surgery model. Methods Rats aged 18 to 20 months were randomly allocated to the following groups: naïve, abdominal surgery alone, or minocycline injection before abdominal surgery. Hippocampal cytokine mRNA levels were measured at 3 hours, 1 day, 3 days, and 7 days after surgery, and microglial activation was measured at 3 hours and 7 days after surgery. Memory was assessed using the Morris water maze test. Results Surgery resulted in severe cognitive impairment in aged rats and induced a significant neuroinflammatory response and microglial activation. The use of minocycline can prevent microglial activation after surgery, but delayed microglial activation may occur. The use of minocycline may further impair memory after surgery. Conclusion Minocycline can restrain microglial activation and restrict the inflammatory response in the hippocampus early after surgery, but it may induce delayed microglial activation and cannot prevent POCD in aged rats.
目的 术后认知功能障碍（POCD）在老年患者术后很常见，且与高发病率相关。POCD的分子机制尚不清楚。米诺环素是一种小胶质细胞激活抑制剂，可能对治疗和预防POCD有用。我们探讨了米诺环素是否能抑制老年大鼠（作为手术模型）的小胶质细胞激活并预防POCD。方法 将18至20月龄的大鼠随机分为以下几组：未处理组、单纯腹部手术组或腹部手术前注射米诺环素组。在术后3小时、1天、3天和7天测量海马细胞因子mRNA水平，并在术后3小时和7天测量小胶质细胞激活情况。使用莫里斯水迷宫试验评估记忆。结果 手术导致老年大鼠出现严重的认知障碍，并引发显著的神经炎症反应和小胶质细胞激活。使用米诺环素可预防术后小胶质细胞激活，但可能会出现延迟的小胶质细胞激活。使用米诺环素可能会进一步损害术后记忆。结论 米诺环素可在术后早期抑制小胶质细胞激活并限制海马体中的炎症反应，但可能会诱导延迟的小胶质细胞激活，且不能预防老年大鼠的POCD。
