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目的 探究氧化苦参碱（OMT）对急性一氧化碳（CO）中毒大鼠脑损伤的保护作用及潜在机制。方法 选取100只健康成年雄性Sprague-Dawley大鼠，标准实验室环境中适应性饲养，自然光照周期，自由摄取水和食物。饲养至第8日，随机分为空白对照组（NC组）、急性CO中毒模型组（CO组）、急性CO中毒模型辅以OMT治疗组（OMT组）及急性CO中毒模型联合OMT与SIRT1抑制剂治疗组（OMT+EX527组），每组25只大鼠。借由吸入CO气体构建急性CO中毒大鼠模型，OMT组接受OMT 200 mg/kg灌胃处理，OMT+EX527组予OMT 200 mg/kg与SIRT1抑制剂EX5271 mg/kg灌胃处理。通过进行Morris水迷宫实验来评估各组大鼠的学习与记忆能力；制备脑组织样本，行HE染色以检测各组大鼠脑组织形态，行TUNEL染色检测各组大鼠大脑细胞凋亡情况，采用透射电子显微镜观察各组大鼠神经细胞超微结构，借助流式细胞仪检测各组大鼠线粒体膜电位，采用活性氧试剂盒检测各组大鼠海马组织活性氧水平，通过Western blot实验分析各组大鼠海马组织SIRT1、FOXO1、Nrf-2及Bcl-2蛋白表达。结果 与CO组比较，OMT组大鼠逃避潜伏期缩短，且穿越平台次数显著增多（P<0.01）；与CO组和OMT+EX527组比较，OMT组大鼠脑组织细胞形态结构得以改善；与CO组和OMT+EX527组比较，OMT组大鼠TUNEL阳性细胞率降低（P<0.01）；与CO组和OMT+EX527组比较，OMT组大鼠海马区神经细胞平均荧光强度提升（P<0.01）;OMT组与CO组和OMT+EX527组比较，海马组织活性氧水平降低（P<0.01）;OMT组和CO组比较，海马组织SIRT1、FOXO1、Nrf-2、Bcl-2蛋白表达水平升高（P<0.05）。结论 OMT或许通过激活SIRT1/FOXO1信号通路、改善神经细胞线粒体功能、减轻氧化应激损伤，从而对急性CO中毒大鼠的脑损伤起到保护作用。
Abstract：Objective To investigate the protective effects and potential mechanisms of oxymatrine(OMT) on brain injury in rats with acute carbon monoxide(CO) poisoning. Methods One hundred healthy adult male Sprague-Dawley rats were selected and adapted to standard laboratory conditions with natural light cycles and free access to water and food. On day 8 of feeding, they were randomly divided into four groups: control group(NC group), acute CO poisoning model group(CO group), acute CO poisoning model supplemented with OMT treatment group(OMT group), and acute CO poisoning model combined with OMT and silent information regulator 2 homolog(SIRT1) inhibitor treatment group(OMT+EX527 group), with 25 rats in each group. An acute CO poisoning model was established by CO gas inhalation. The OMT group received OMT at 200 mg/kg via gastric intubation, while the OMT+EX527 group received OMT at 200 mg/kg and SIRT1 inhibitor EX527 at 1 mg/kg via gastric intubation. The learning and memory abilities of rats in each group were evaluated through the Morris water maze test. Brain tissue samples were prepared and stained with HE to examine the morphology of brain tissues in each group. TUNEL staining was performed to detect apoptosis in brain cells of each group, and transmission electron microscopy was used to observe the ultrastructure of neurons in each group. Flow cytometry was employed to measure mitochondrial membrane potential in each group. Reactive oxygen species(ROS) levels in hippocampal tissues were determined using a ROS assay kit. Western blot analysis was conducted to assess the expression of SIRT1, FOXO1, Nrf-2, and Bcl-2 proteins in hippocampal tissues of each group. Results Compared with the CO group, the OMT group exhibited a shortened latency period for escape and a significantly increased number of platform crossings(P<0.01). Compared with the CO group and OMT+EX527 group, the morphological structure of brain tissue cells in the OMT group was improved, while the rate of TUNEL-positive cells in the OMT group was reduced(P<0.01). Compared with the CO group and OMT+EX527 group, the average fluorescence intensity of neurons in the hippocampus of the OMT group was increased(P<0.01), while the ROS level in the hippocampal tissues of the OMT group was decreased(P<0.01). Compared with the CO group, the expression levels of SIRT1, FOXO1, Nrf-2, and Bcl-2 proteins in hippocampal tissues of the OMT group were elevated(P<0.05). Conclusion OMT may protect against acute COinduced brain injury by activating SIRT1/FOXO1 signaling pathway, improving mitochondrial function in neuronal cells and alleviating oxidative stress.
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基本信息:
DOI：10.13431/j.cnki.immunol.j.20260015
中图分类号:R285.5
引用信息:
[1]高莹,张俊英,房娉平,等.氧化苦参碱对急性一氧化碳中毒大鼠脑损伤的保护作用及潜在机制分析[J].免疫学杂志,2026,42(02):103-108.DOI:10.13431/j.cnki.immunol.j.20260015.
基金信息:
河北省医学科学研究课题计划项目（20240788）
2026-02-28
2026-02-28