火麻仁油及大麻二酚对抑郁模型小鼠行为及炎症反应的影响

王语聪; 谢智鑫; 李春雨; 王宇晴; 陈晓伟; 韩建春

doi:10.13386/j.issn1002-0306.2020060238

火麻仁油及大麻二酚对抑郁模型小鼠行为及炎症反应的影响

Effects of Hemp Seed Oil and Cannabidiol on Behavior and Inflammation in Depression Model Mice

摘要

摘要: 目的：探究火麻仁油及大麻二酚（Cannabidiol，CBD）对慢性不可预测的轻度应激（Chronic unpredictable mild stress，CUMS）模型小鼠行为学及炎症因子的影响。方法：将50只雄性C57BL/6小鼠随机分成5组：空白组、模型组、火麻仁油组（3 mL/kg）、CBD低剂量组（15 mg/kg）、CBD高剂量组（30 mg/kg），试验周期8周，测定小鼠抑郁、焦虑、学习认知能力及炎症因子（肿瘤坏死因子（TNF-α）、白细胞介素-1（IL-1β）和诱导NOS（iNos））的mRNA表达及小胶质细胞的离子化的钙结合衔接分子1（IBA-1）的蛋白表达。结果：与空白组相比，模型组在抑郁和焦虑行为及学习和认知功能有显著差异（P<0.05; P <0.01）；与模型组相比，CBD剂量组均显著改善模型小鼠的抑郁焦虑行为并提高了学习认知功能（P<0.05; P<0.01)，火麻仁油组显著改善小鼠的蔗糖偏好指数和新物体识别能力（P<0.05）。与空白组相比，模型组小鼠的皮层和海马组织中TNF-α、IL-1β和iNos mRNA表达量显著升高（P<0.05; P<0.01）；与模型组相比，CBD剂量组的皮层和海马TNF-α、IL-1β和iNos mRNA表达量均显著降低（P<0.05; P<0.01）；火麻仁油组皮层、海马TNF-α和iNos无显著性差异（P>0.05)。免疫组化结果显示，火麻仁油和CBD均抑制炎症介质小胶质细胞的离子化的钙结合衔接分子1（IBA-1）的表达。结论：CUMS小鼠建模成功，火麻仁油能够提高小鼠的抑郁行为及认知能力，并且降低IL-1β表达，CBD可改善小鼠的焦虑症状、提升学习和认知功能，抑制脑组织皮层和海马的炎症反应，从而证明火麻仁油和CBD对CUMS模型小鼠具有一定的作用。

Abstract: Objective: To explore the effects of hemp seed oil and Cannabidiol (CBD) on the behavior and inflammatory factors of chronic unpredictable mild stress (CUMS) mice. Methods: 50 male C57BL/6 mice were randomly divided into 5 groups: Blank group, model group, hemp seed oil group (3 mL/kg), CBD low-dose (15 mg/kg), CBD high-dose group (30 mg/kg), and gavage was continued for 8 weeks. The expression of depression, anxiety, learning and cognitive ability and inflammatory factors (tumor necrosis factor (TNF-α), interleukin-1 (IL-1β) and induced NOS (iNos)) were measured in mice. Results: Compared with the blank group, the model group had significant differences in depression and anxiety behavior and learning and cognitive functions (P<0.05; P<0.01); compared with the model group, the CBD dose group significantly improved the model mice from the depressive and anxious behavior of mice to the cognitive function of learning (P<0.05; P<0.01); besides, the hemp seed oil group significantly improved the sucrose preference index and new object recognition ability in mice (P<0.05). Compared with the blank group, the expression of TNF-α, IL-1β and iNos mRNA in the cortex and hippocampus of the model group significantly increased (P<0.05; P<0.01); compared with the model group, CBD dose groups showed that the expression of TNF-α, IL-1β and iNos mRNA in the cortex and hippocampus significantly decreased (P<0.05; P<0.01); There was no significant difference in TNF-α and iNos in cortex and hippocampus of the hemp seed oil group(P>0.05). The results of immunohistochemistry showed that hemp seed oil and CBD both inhibited the expression of ionized calcium-binding adaptor molecule 1 (IBA-1) of inflammatory mediator microglia. Conclusion: CUMS mice are successfully modeled. Hemp oil can partially improve the depressive behavior and cognitive ability of mice and reduce the expression of IL-1β. The CBD can improve the anxiety symptoms of mice, increase learning and cognitive functions, and inhibit the cortex and hippocampus of brain tissue. The inflammatory response of hemp seed oil and CBD has a certain effect on CUMS model mice.