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| 菊苣酸对脓毒症相关性脑病小鼠认知功能的影响 |
| Effect of chicoric acid on cognitive function in mice with sepsis-associated encephalopathy |
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| DOI：10.12089/jca.2022.02.016 |
| 中文关键词: 菊苣酸 脓毒症相关脑病 氧化应激 炎症反应 认知功能 |
| 英文关键词: Chicorc acid Sepsis-associated encephalopathy Oxidative stress Inflammatory response Cognitive function |
| 基金项目:江西省卫生健康委员会中医药科技计划（2018B007）；江西省卫生健康委员会中医药科技计划（2020A0326） |
| 作者 | 单位 | E-mail | | 高红艺 | 330006,江西省南昌大学第二附属医院麻醉与围术期医学科,江西省麻醉学重点实验室,十堰市太和医院 | | | 申云鹏 | 330006,江西省南昌大学第二附属医院麻醉与围术期医学科,江西省麻醉学重点实验室 | | | 袁佳佳 | 330006,江西省南昌大学第二附属医院麻醉与围术期医学科,江西省麻醉学重点实验室 | | | 徐真珍 | 330006,江西省南昌大学第二附属医院麻醉与围术期医学科,江西省麻醉学重点实验室 | | | 胡衍辉 | 330006,江西省南昌大学第二附属医院麻醉与围术期医学科,江西省麻醉学重点实验室 | | | 徐国海 | 330006,江西省南昌大学第二附属医院麻醉与围术期医学科,江西省麻醉学重点实验室 | | | 陈勇 | 330006,江西省南昌大学第二附属医院麻醉与围术期医学科,江西省麻醉学重点实验室 | chenyongdaniel@126.com |
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| 中文摘要: |
目的 探讨菊苣酸对脓毒症相关性脑病（SAE）小鼠认知功能的影响。
方法 健康雄性C57BL/6小鼠60只，6～8周龄，体重20～25 g。采用随机数字表法将小鼠分为四组：假手术组（S组）、脓毒症组（P组）、菊苣酸组（CA组）和菊苣酸+SIRT1抑制剂EX527组（CE组），每组15只。P组、CA组和CE组行盲肠结扎穿孔（CLP）。CA组和CE组进行CLP术前分别腹腔注射菊苣酸50 mg/kg、菊苣酸50 mg/kg+EX527.5 mg/kg，连续7 d，S组和P组每日注射等剂量溶剂。每组取9只小鼠于CLP术前、术后3、5、7 d采用Morris水迷宫进行认知功能测试；每组取6只小鼠于CLP术后1 d断头取出海马组织，采用化学比色法检测海马组织超氧化物歧化酶（SOD）和丙二醛（MDA）浓度，ELISA法测定海马组织TNF-α及IL-6浓度，Western blot法检测海马组织SIRT1、磷酸化NF-κB（p-NF-κB）及IκBα蛋白含量，光镜下观察海马组织的病理学变化。
结果 与S组比较，P组、CA组和CE组术后逃避潜伏期明显延长（P<0.05），穿越平台次数明显减少（P<0.05），海马组织SOD浓度、SIRT1及IκBα蛋白含量明显降低（P<0.05），MDA、TNF-α、IL-6浓度及p-NF-κB蛋白含量均明显升高（P<0.05）。与P组比较，CA组和CE组逃避潜伏期明显缩短（P<0.05），穿越平台次数明显增加（P<0.05），海马组织SOD浓度、SIRT1及IκBα蛋白含量明显升高（P<0.05），MDA、TNF-α、IL-6浓度及p-NF-κB蛋白含量均明显降低（P<0.05）。与CA组比较，CE组术后逃避潜伏期明显延长（P<0.05），穿越平台次数明显减少（P<0.05），海马组织SOD浓度、SIRT1及IκBα蛋白含量明显降低（P<0.05），MDA、TNF-α、IL-6浓度及p-NF-κB蛋白含量均明显升高（P<0.05）。
结论 菊苣酸可改善SAE小鼠认知功能，其机制可能与菊苣酸上调SIRT1/NF-κB表达、抑制海马氧化应激损伤及炎症反应有关。 |
| 英文摘要: |
Objective To investigate the effect of chicoric acid on cognitive function in mice with sepsis-associated encephalopathy (SAE).
Methods Sixty healthy male C57BL/6 mice, aged 6-8 weeks and weighing 20-25 g, were randomly divided into four groups by random number table method: sham operation group (group S), sepsis group (group P)， chicoric acid (group CA) and chicoric acid+EX527 group (group CE), 15 mice in each group. SAE model was reproduced by cecum ligation perforation in group P. The mice in groups CA and CE were intraperitoneal injected with chicoric acid 50 mg/kg and chicoric acid 50 mg/kg + EX527.5 mg/kg respectively one week before the preparation of SAE model. The mice in groups S and P were injected with the same dose of solvent daily. Morris water maze was performed on mice to test cognitive function before CLP, 3, 5 and 7 days after CLP. Hippocampal tissues of mice were collected on the first day after operation. Then superoxide dismutase (SOD) and malondialdehyde (MDA) activities in the hippocampus were detected by chemical colometry. The concentrations of TNF-α and IL-6 in the hippocampus were determined by ELISA, and the expressions of SIRT1, p-NF-κB and IκBα in the hippocampus were detected by Western blot. Their hippocampus were observed for the pathological changes.
Results Compared with group S, the escape latency was significantly prolonged (P < 0.05), the frequency of crossing the original platform was significantly decreased (P < 0.05), the concentration of SOD, the expressions of SIRT1 and IκBα in the hippocampus were significantly decreased (P < 0.05), the concentration of MDA, TNF-α, IL-6 and the expressions of p-NF-κB were significantly increased (P < 0.05) in other three groups. Compared with group P, the escape latency was significantly shortened (P < 0.05), the frequency of crossing the original platform was significantly increased (P < 0.05), the concentration of SOD, the expressions of SIRT1 and IκBα in the hippocampus were significantly increased (P < 0.05), the concentration of MDA, TNF-α, IL-6 and expressions of p-NF-κB were significantly decreased (P < 0.05) in groups CA and CE. Compared with group CA, the escape latency was significantly prolonged (P < 0.05), the frequency of crossing the original platform was significantly decreased (P < 0.05), the concentration of SOD, the expressions of SIRT1 and IκBα in the hippocampus were significantly decreased （P < 0.05）， the concentration of MDA, TNF-α, IL-6 and expressions of p-NF-κB were significantly increased (P < 0.05) in group CE.
Conclusion The chicoric acid can improve the cognitive function with sepsis-associated encephalopathy in mice, which may be associated with up-regulated expression of SIRT1/NF-κB, and inhibiting the oxidative stress damage and inflammatory response of hippocampus． |
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