抗氧化剂SS-31对异氟醚麻醉小鼠脑源性神经营养因子信号通路及认知功能的影响

摘要

目的：观察线粒体抗氧化肽 SS-31对异氟醚麻醉小鼠脑源性神经营养因子（BDNF）信号通路及认知功能的影响。方法：老年雄性C57BL/6小鼠42只随机均分为3组（n=14）：氧气+生理盐水（Con）组、异氟醚+生理盐水（Iso）组和异氟醚+SS-31（SS-31）组，分别于氧气或异氟醚吸入前30 min腹腔注射等容生理盐水或SS-31（5 mg·kg-1）。气体吸入2 h后各组取6只小鼠检测海马组织中活性氧自由基（ROS）、三磷酸腺苷（ATP）、BDNF、酪氨酸激酶B 受体（TrkB）、磷酸化TrkB（p-TrkB）和磷酸化环磷酸腺苷反应元件结合蛋白（p-CREB）水平；24 h后各组余8只小鼠行旷场实验和条件恐惧性实验。结果：与Iso组比较，SS-31组ROS水平降低， ATP、BDNF、p-TrkB和p-CREB水平升高，24 h场景实验僵直时间增加（P<0.05）。结论：SS-31可改善异氟醚麻醉所致小鼠认知功能损伤，这可能与其清除线粒体内ROS，增加ATP产生，激活BDNF通路有关。%Objective: To observe the effects of antioxidant SS-31 on brain-derived neurotrophic factor (BDNF) pathway and cognitive function in aged mice after isoflurane anesthesia. Methods: Forty-two old male C57BL/6 mice were randomly divided into three groups (n=14): oxygen + saline group (Con group), isoflurane + saline group (Iso group), and isoflurane + SS-31 group (SS-31 group). SS-31 (5 mg·kg-1) or normal saline was intraperitoneally administered with a volume of 0.4 mL·kg-1 30 min before oxygen or isoflurane inhalation. After two hours of gas inhalation, six mice in each group were immediately decapitat-ed. The hippocampus was rapidly removed to determine the level of reactive oxygen species (ROS) and adenosine triphosphate (ATP), and measure the content of BDNF, tropomyosin receptor kinase B (TrkB), p-TrkB and p-CREB (cAMP response element-binding protein). The other eight mice in each group were used for open field test and fear conditioning test 24 hours after the experiment. Results: Compared with the Iso group, the level of ROS was decreased while the level of ATP, the content of BDNF, p-TrkB and p-CREB, and the freezing time to context were increased in the SS-31 group (P<0.05). Conclusion: Mito-chondrial antioxidant SS-31 scavenges mitochondrial ROS, increases ATP, facilitates the regulation of BDNF signaling pathway, and attenuates isoflurane-induced cognition impairments.