Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.
Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.
Neurochem Int. 2021 Sep;148:105078. doi: 10.1016/j.neuint.2021.105078. Epub 2021 May 25.
As a general anesthetic widely used in surgical, sevoflurane has been shown to cause cognitive and memory deficits in the elderly. It's important to find out agents that can counteract sevoflurane-induced cognitive dysfunction. This study is aimed to investigate the effect of lovastatin on sevoflurane-induced cognitive impairment in aged rats and reveal the potential mechanisms. BV-2 cells, rat hippocampal neurons or male aged rats were exposed to 2% sevoflurane for 5 h. The cells were pretreated with 10 μM lovastatin. The rats were intraperitoneally injected with 5 mg/kg/day lovastatin for three days. The results showed that lovastatin enhanced exosomal IDE secretion from sevoflurane-exposed BV-2 cells and promoted Aβ degradation. Lovastatin treatment also inhibited the increased expressions of β-secretase 1 (BACE1) and γ-secretase in hippocampal neurons under sevoflurane exposure in vitro. In animal experiments, the discrimination index in novel object recognition test and percentage of spontaneous alternation in Y-maze test were significantly elevated after lovastatin administration. In addition, Aβ plaque area and contents of soluble Aβ and Aβ in the hippocampal tissues were decreased upon lovastatin treatment. Furthermore, lovastatin reversed sevoflurane-induced Aβ accumulation via up-regulating IDE expression, and down-regulating amyloid precursor protein (APP)-related protein expression (β-C-terminal fragment (CTF), BACE1 and γ-secretase). In conclusion, lovastatin alleviates sevoflurane-induced cognitive deficient in aged rats via promoting Aβ degradation and reducing Aβ production. Lovastatin may be beneficial in preventing anesthetic-induced cognitive impairment.
七氟醚作为一种广泛应用于外科手术的全身麻醉剂，已被证明会导致老年人认知和记忆功能受损。寻找可以对抗七氟醚引起的认知功能障碍的药物非常重要。本研究旨在探讨洛伐他汀对老龄大鼠七氟醚诱导认知障碍的影响，并揭示其潜在机制。将 BV-2 细胞、大鼠海马神经元或雄性老龄大鼠暴露于 2%七氟醚中 5 小时。用 10μM 洛伐他汀预处理细胞。大鼠连续 3 天腹腔注射 5mg/kg/天洛伐他汀。结果表明，洛伐他汀增强了七氟醚暴露的 BV-2 细胞中外泌体 IDE 的分泌，并促进了 Aβ 的降解。洛伐他汀治疗还抑制了体外七氟醚暴露下海马神经元中β-分泌酶 1（BACE1）和 γ-分泌酶表达的增加。在动物实验中，洛伐他汀给药后，新物体识别测试中的辨别指数和 Y 迷宫测试中的自发交替百分比显著升高。此外，洛伐他汀处理后，海马组织中 Aβ 斑块面积和可溶性 Aβ 及 Aβ 含量降低。此外，洛伐他汀通过上调 IDE 表达和下调淀粉样前体蛋白（APP）相关蛋白表达（β-羧基端片段（CTF）、BACE1 和 γ-分泌酶），逆转了七氟醚诱导的 Aβ 积聚。综上所述，洛伐他汀通过促进 Aβ 降解和减少 Aβ 生成，减轻老龄大鼠七氟醚诱导的认知缺陷。洛伐他汀可能有益于预防麻醉诱导的认知障碍。
