[关键词]
[摘要]
目的 观察隐丹参酮对慢性不可预见应激(CUMS)联合脂多糖(LPS)所致抑郁小鼠氧化应激和炎症反应的影响。方法 60只清洁级ICR小鼠随机分为对照组、模型组、帕罗西汀组(20 mg/kg)及隐丹参酮低、中、高剂量(10、20、40 mg/kg)组,每组10只。采用CUMS+LPS应激刺激14 d建立抑郁模型(除对照组),同时ig相应药物或生理盐水,1次/d,连续14 d。通过体质量增量、糖水偏好指数、悬尾实验及新奇环境摄食测试评价抑郁行为,并测定各组血清超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA),海马和皮质白细胞介素(IL)-6、IL-1β、肿瘤坏死因子(TNF)-α变化情况。结果 隐丹参酮20、40 mg/kg组体质量增量及SOD、CAT、GSH-Px酶活性高于模型组,不动时间短于模型组(P<0.05、0.01),海马IL-6、海马和皮质IL-1β含量低于模型组(P<0.05、0.01)。各治疗组糖水偏好指数高于模型组、摄食潜伏期短于模型组(P<0.05、0.01),血清MDA、皮质TNF-α含量低于模型组(P<0.05、0.01)。隐丹参酮40 mg/kg组皮质IL-6、海马TNF-α含量低于模型组(P<0.01)。结论 隐丹参酮对CUMS联合LPS致小鼠抑郁症状有改善作用,其机制可能与抑制过强的氧化应激反应与神经炎症反应,并减轻神经元损伤有关。
[Key word]
[Abstract]
Objective To observe the effects of cryptotanshinone on oxidative stress and inflammatory response in depressed mice induced by chronic unpredictable stress (CUMS) combined with lipopolysaccharide (LPS). Methods Sixty clean grade ICR mice were randomly divided into control group, model group, paroxetine group (20 mg/kg), cryptotanshinone low-dose, medium-dose, and high-dose (10, 20, 40 mg/kg), with 10 mice in each group. Depression model was established by CUMS + LPS stress stimulation for 14 d. At the same time, relevant drugs or normal saline were given intragastrically, once daily, for consecutive 14 d. Depressive behaviors were evaluated by body weight gain, sugar water preference index, tail suspension test, and novel environmental feeding test, and serum superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX) and malondialdehyde (MDA) were determined. Changes of interleukin (IL-6), IL-1β, tumor necrosis factor (TNF) -α in hippocampus and cortex were determined. Results Body weight increment, SOD, CAT, and GSH-Px enzyme activities in 20 and 40 mg/kg cryptotanshinone groups were higher than those in model group, and immobility time was shorter than that in model group (P < 0.05, 0.01). The contents of IL-6 in hippocampus, and IL-1β in hippocampus and cortex were lower than those in model group (P < 0.05, 0.01). The preference index of sugar water in treatment groups was higher than that in model group, and the incubation period of ingestion was shorter than that in model group (P < 0.05, 0.01). The contents of MDA in serum and TNF-α in cortex were lower than those in model group (P < 0.05, 0.01). The contents of IL-6 in cortex and TNF-α in hippocampus of cryptotanshinone 40 mg/kg group were lower than those of model group (P < 0.01). Conclusion Cryptotanshinone can improve the depressive symptoms of CUMS + LPS mice, and the mechanism may be related to the inhibition of excessive oxidative stress response, and neuroinflammatory response, and the alleviation of neuronal injury.
[中图分类号]
R965
[基金项目]
福建省中青年教师教育科研项目(JAT171155);泉州市指导性科技计划项目(2021N130S)