Anesthesia and Operation Center, the First Medical Center, Chinese PLA General Hospital, 28th Fuxing Road, Haidian District, Beijing 100853, China; Department of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, 10th Tieyi Road, Haidian District, Beijing, 100038, China.
Department of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, 10th Tieyi Road, Haidian District, Beijing, 100038, China.
Neurosci Lett. 2021 Jan 1;740:135461. doi: 10.1016/j.neulet.2020.135461. Epub 2020 Oct 25.
Elderly patients receive propofol at regular intervals for sedation during gastrointestinal endoscopy. However, the link between cognition and intermittent propofol exposure remains unclear. Thus, we used aged rats to investigate the effect of propofol on cognition.
The study included two parts. In the first part, aged (18-20 months old) male Sprague-Dawley rats underwent intermittent intraperitoneal injection of propofol (200 mg/kg) or intralipid, every 9 days or once a day. In the second part, some aged rats received intraperitoneal injection of Bay 11-7082 (1 mg/kg), a specific inhibitor of NF-κB, 30 min before propofol injection. Memory tests were performed to evaluate cognition 24 h after the entire treatment. The hippocampal neuronal damage was assessed by TUNEL staining. The hippocampal levels of p-NF-κB p65, NLRP3, caspase-1 p20, and cleaved caspase-3 were detected by western blotting. The hippocampal and serum levels of IL-1β, IL-6, and TNF-α were evaluated using ELISA.
There were no differences in the behavioral tests, hippocampal neuronal damage, and neuroinflammation between groups given intralipid and propofol treatment every 9 days. However, repeated propofol treatment once a day promoted activation of NF-κB and the NLRP3 inflammasome, inducing cognitive impairment and neuroinflammation. Interestingly, pretreatment with Bay-11-7082 not only inhibited NF-κB/NLRP3 inflammasome activation, but also attenuated neuronal damage and cognitive dysfunction in aged rats exposed to daily propofol treatment.
Intermittent propofol treatment every 9 days may be safe for aged rats. However, propofol treatment once a day could impair the cognition of aged rats, partly through the activation of the NF-κB pathway and NLRP3 inflammasome, which may be a potential targets for the treatment of cognitive impairment in elderly patients.
老年患者在接受胃肠道内镜检查时，会定期接受异丙酚镇静。然而，认知功能与异丙酚间歇性暴露之间的联系尚不清楚。因此，我们使用老年大鼠来研究异丙酚对认知功能的影响。
该研究包括两部分。在第一部分中，18-20 月龄雄性 Sprague-Dawley 大鼠接受异丙酚（200mg/kg）或脂肪乳剂的间歇性腹腔注射，每 9 天或每天一次。在第二部分中，一些老年大鼠在异丙酚注射前 30 分钟接受 NF-κB 特异性抑制剂 Bay 11-7082（1mg/kg）腹腔注射。在整个治疗结束后 24 小时进行记忆测试，以评估认知功能。TUNEL 染色评估海马神经元损伤。Western blot 检测海马组织 p-NF-κB p65、NLRP3、caspase-1 p20 和 cleaved caspase-3 的表达。ELISA 检测海马和血清中 IL-1β、IL-6 和 TNF-α的水平。
脂肪乳剂和异丙酚每 9 天治疗组之间的行为测试、海马神经元损伤和神经炎症无差异。然而，每天重复一次异丙酚治疗可促进 NF-κB 和 NLRP3 炎性小体的激活，导致认知障碍和神经炎症。有趣的是，Bay-11-7082 预处理不仅抑制了 NF-κB/NLRP3 炎性小体的激活，还减轻了老年大鼠每日异丙酚处理后的神经元损伤和认知功能障碍。
每 9 天间歇性异丙酚治疗可能对老年大鼠是安全的。然而，每天一次的异丙酚治疗可能会损害老年大鼠的认知功能，部分原因是 NF-κB 通路和 NLRP3 炎性小体的激活，这可能是治疗老年患者认知障碍的潜在靶点。
