木犀草素通过调控HMGB1改善脓毒症小鼠模型的认知功能障碍

Luteolin can improve cognitive dysfunction in septic mice by regulating HMGB1

关键词:  脓毒症性脑病  木犀草素  认知功能障碍  高迁移率族蛋白B1  小鼠

Key words:  sepsis associated encephalopathy  luteolin  cognitive dysfunction  high mobility group box 1 protein  mouse

摘要:

[目的] 探究木犀草素通过调控高迁移率族蛋白B1（HMGB1）对脓毒症性脑病（SAE）小鼠模型认知功能障碍的影响。[方法] 将小鼠随机分为6组：假手术组，模型组，木犀草素低、中、高剂量组和地塞米松组。通过盲肠结扎和穿刺诱导小鼠脓毒症。旷场实验和Morris水迷宫检测小鼠活动探索及学习认知能力；苏木精-伊红（HE）染色检测脑组织损伤；原位末端标记技术（TUNEL）染色检测神经细胞凋亡；酶联免疫吸附（ELISA）法检测白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）水平；试剂盒检测超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH）含量；蛋白免疫印迹（Western Blot）法检测HMGB1蛋白表达水平。[结果] 与模型组比较，木犀草素中、高剂量组和地塞米松组小鼠存活率升高（P<0.05），总行驶距离和中央区域停留时间增加（P<0.05），逃避潜伏期时间缩短（P<0.05），目标象限时间、穿越区域次数提高（P<0.05），海马区组织病理损伤程度减轻，神经细胞凋亡率降低（P<0.05），IL-6、IL-1β、TNF-α水平降低（P<0.05），SOD、GSH含量升高（P<0.05），MDA含量降低（P<0.05），HMGB1蛋白水平降低（P<0.05）。加入HMGB1抑制剂甘草酸后能够部分逆转木犀草素对SAE小鼠模型认知障碍、炎症水平、神经细胞凋亡和氧化应激的影响。[结论] 木犀草素可以通过调控HMGB1改善SAE小鼠模型的认知功能障碍。

Abstract:

[Objective] To investigate the effect of luteolin on cognitive dysfunction in sepsis associated encephalopathy mice by regulating high mobility group box 1 protein (HMGB1).[Methods] Mice with sepsis induced by cecal ligation and puncture were randomly divided into 6 groups:Sham group, model group, luteolin low, medium and high dose group and dexamethasone group. The open field test and Morris water maze were used to detect the activity exploration, learning and cognition of mice. Brain injury was detected by HE staining. TUNNEL staining was used to detect neuronal apoptosis. Levels of interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor(TNF-α) were detected by ELISA. The contents of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) were detected by the kit. Western blotting was used to detect HMGB1 protein expression.[Results] Compared with model group, luteolin medium, high dose group and dexamethasone group significantly increased survival rate of mice (P<0.05), total distance and a significant rise in the central area residence time (P<0.05), the escape latency time significantly reduced (P<0.05), a significant rise in target quadrant time, through the regional times (P<0.05), the hippocampus tissue pathological damage, nerve cells apoptosis rate was significantly lower (P<0.05);IL-6, IL-1β, TNF-α were significantly reduced(P<0.05);SOD and GSH contents increased significantly(P<0.05);MDA content decreased significantly (P<0.05), and HMGB1 protein level decreased significantly (P<0.05). The addition of HMGB1 inhibitor glycyrrhizin reversed the effect of luteolin on the sepsis associated encephalopathy mice model.[Conclusion] Luteolin can improve cognitive dysfunction in sepsis associated encephalopathy mice by regulating HMGB1.