【摘要】 目的:研究牛蒡子苷元对七氟烷麻醉后大鼠炎症反应和认知功能障碍的影响,并初步探讨其作用机制。方法:雄性SPF级SD大鼠50只,随机分为对照组、七氟烷组及牛蒡子苷元低(5 mg·kg^-1)、中(10 mg·kg^-1)、高(20 mg·kg^-1)剂量组,每组10只。除对照组外,其余组大鼠采用6%七氟烷麻醉。牛蒡子苷元各剂量组大鼠在麻醉前腹腔注射200μL牛蒡子苷元溶液,对照组和七氟烷组大鼠腹腔注射等体积二甲基亚砜（dimethyl sulfoxide, DMSO）。干预48 h后,Morris水迷宫实验检测大鼠空间学习记忆能力;酶联免疫吸附测定实验（enzyme linked immunosorbent assay, ELISA）检测血清炎症因子白细胞介素-6（interleukin-6,IL-6）、IL-1β和肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）的水平;苏木精-伊红（hematoxylin-eosin, HE）染色观察海马组织病理学改变;原位缺口末端标记法（terminal-deoxynucleotidy transferase mediated nick end labeling, TUNEL）分析各组大鼠海马组织神经元凋亡水平;蛋白质免疫印迹（Western Blot）和免疫组织化学法检测大鼠海马组织C1q/肿瘤坏死因子相关蛋白6（C1q/tumor necrosis factor-related protein 6,CTRP6）、蛋白激酶B（protein kinase B,Akt）、p-Akt、核转录因子-κB（nuclear transcription factor-κB,NF-κB）、p-NF-κB蛋白表达水平。结果:与对照组比较,七氟烷组大鼠逃避潜伏期显著延长（P<0.05）,穿台指数及CTRP6蛋白表达水平显著降低（P<0.05）,血清IL-6、IL-1β、TNF-α的含量及p-Akt/Akt和p-NF-κB/NF-κB的水平显著升高（P<0.05）,海马CA1区病理损伤显著,神经元凋亡指数显著升高（P<0.05）;与七氟烷组比较,牛蒡子苷元各剂量组大鼠逃避潜伏期显著缩短（P<0.05）,穿台指数及CTRP6蛋白表达显著增加（P<0.05）,血清IL-6、IL-1β、TNF-α的含量及p-Akt/Akt和p-NF-κB/NF-κB的水平显著降低（P<0.05）,海马CA1区病理损伤明显改善,神经元凋亡指数显著降低（P<0.05）。结论:牛蒡子苷元能明显改善七氟烷麻醉诱发的大鼠神经性炎症反应和认知功能障碍,其作用可能与调控CTRP6/Akt/NF-κB信号通路相关。更多还原

【Abstract】 Objective: To study the effects of arctigenin on inflammatory response and cognitive dysfunction in rats after sevoflurane anesthesia, and to explore its mechanism.Methods: Fifty male SPF SD rats were randomly divided into control group, sevoflurane group and arctigenin low(5 mg·kg^-1),medium(10 mg·kg^-1) and high(20 mg·kg^-1) dose groups, with 10 rats in each group.Except the control group, rats in other groups were anesthetized with 6% sevoflurane.Before anesthesia, rats in each dose of arctigenin were injected intraperitoneally with 200 μL of arctigenin solution, and rats in the control and sevoflurane groups were intraperitoneally injected with equal volumes of dimethyl sulfoxide（DMSO）.After 48 hours of intervention, Morris water maze test was used to detect the spatial learning and memory ability of rats; enzyme linked immunosorbent assay（ELISA） was used to detect serum inflammatory factors interleukin-6（IL-6）,IL-1β and tumor necrosis factor-α（TNF-α） level; hematoxylin-eosin（HE） staining was used to observe the histopathological changes of hippocampus; terminal-deoxynucleotidy transferase mediated nick end labeling（TUNEL） was used to analyze the level of neuronal apoptosis in hippocampus of rats in each group; Western Blot and immunohistochemistry were used to detect C1 q/tumor necrosis factor-related protein 6（CTRP6）,protein kinase B（Akt）,p-Akt and nuclear transcription factor-κB（NF-κB）,p-NF-κB protein expression level.Results: Compared with the control group, the escape latency of sevoflurane group was significantly prolonged（P<0.05）,the penetration index and the expression level of CTRP6 protein were significantly decreased（P<0.05）,the levels of serum IL-6,IL-1β,TNF-α p-Akt/Akt and p-NF-κB/NF-κB increased significantly（P<0.05）,the pathological damage of hippocampal CA1 area was significant, and the neuronal apoptosis index increased significantly（P<0.05）.Compared with the sevoflurane group, the escape latency of rats in each dose of arctigenin significantly shortened（P<0.05）,the translocation index and CTRP6 protein expression significantly increased（P<0.05）,and serum IL-6,IL-1β,the content of TNF-α and the levels of p-Akt/Akt and p-NF-κB/NF-κB significantly reduced（P<0.05）,the pathological damage of hippocampal CA1 area significantly improved, and the neuronal apoptosis index significantly reduced（P<0.05）.Conclusion: Arctigenin can significantly improve the neuroinflammatory response and cognitive dysfunction induced by sevoflurane anesthesia in rats, which may be related to the regulation of CTRP6/Akt/NF-κB signaling pathways.更多还原