Qian Xiao-Lan, Zhang Wei, Liu Ming-Zheng, Zhou Yu-Bing, Zhang Jing-Min, Han Li, Peng You-Mei, Jiang Jin-hua, Wang Qing-Duan
Henan Key Laboratory for Pharmacology of Liver Diseases, Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, 40 Daxue Road, Zhengzhou 450052, China; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, China; The Third People Hospital of Henan Province, 98 Funiu Road, Zhengzhou 450052, China.
The First Affiliated Hospital, Zhengzhou University, 1 Jianshe East Road, Zhengzhou 450052, China.
Eur J Pharmacol. 2015 Jan 5;746:206-12. doi: 10.1016/j.ejphar.2014.11.017. Epub 2014 Nov 20.
Postoperative cognitive dysfunction (POCD) is a frequent complication following major surgery in the elderly. However, the exact pathogenic mechanisms are still unknown. Dexmedetomidine, a selective alpha 2 adrenal receptor agonist, was revealed anesthesia and brain protective role. The present study aimed to examine whether dexmedetomdine protects against POCD induced by major surgical trauma under general anesthesia in aged mice. In the present study, cognitive function was assessed by Y-maze. Proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor (TNF-α), apoptosis-related factor caspase-3 and Bax were detected by real-time PCR, Western blot or immunohistochemistry. The results showed that anesthesia alone caused weak cognitive dysfunction on the first day after general anesthesia. Cognitive function in mice with splenectomy under general anesthesia was significantly exacerbated at the first and third days after surgery, and was significantly improved by dexmedetomidine administration. Splenectomy increased the expression of IL-1β, TNF-α, Bax and caspase-3 in hippocampus. These changes were significantly inversed by dexmedetomidine. These results suggest that hippocampal inflammatory response and neuronal apoptosis may contribute to POCD, and selective alpha 2 adrenal receptor excitation play a protective role.
术后认知功能障碍(POCD)是老年患者接受大手术后常见的并发症。然而,其确切的发病机制仍不清楚。右美托咪定是一种选择性α2肾上腺素能受体激动剂,具有麻醉和脑保护作用。本研究旨在探讨右美托咪定是否能预防老年小鼠在全身麻醉下大手术创伤所致的POCD。在本研究中,通过Y迷宫评估认知功能。采用实时PCR、蛋白质免疫印迹或免疫组织化学法检测促炎细胞因子白细胞介素-1β(IL-1β)和肿瘤坏死因子(TNF-α)、凋亡相关因子半胱天冬酶-3和Bax。结果显示,单纯麻醉在全身麻醉后第1天引起轻微的认知功能障碍。全身麻醉下行脾切除术的小鼠在术后第1天和第3天认知功能明显恶化,而给予右美托咪定后明显改善。脾切除术增加了海马中IL-1β、TNF-α、Bax和半胱天冬酶-3的表达。右美托咪定可显著逆转这些变化。这些结果表明,海马炎症反应和神经元凋亡可能与POCD有关,选择性α2肾上腺素能受体激动发挥保护作用。